No description available.

Quatre microélectrodes ont été insérées dans le ganglion stellaire gauche (GS) de préparations canines in vivo pour évaluer la décharge des potentiels d’action dans les neurones situés dans ce ganglion périphérique durant un état cardiovasculaire stable et suivant des injections systémiques et locales de nicotine. Durant les périodes de contrôle, des changements mineurs ont été observés dans la pression artérielle systolique, dans le rythme cardiaque et dans le temps de conduction atrio-ventriculaire. L’activité générée par les neurones du GS est demeurée relativement constante à l’intérieure de chaque chien, mais variait entre les préparations. L’administration de nicotine systémique a altéré les variables physiologiques et augmenté l’activité neuronale. Même si différents changements au niveau des variables physiologiques ont été observés entre les animaux, ces changements demeuraient relativement constants pour un même animal. La dynamique de la réponse neuronale était similaire, mais l’amplitude et la durée variaient entre et au sein des chiens. L’injection de nicotine dans une artère à proximité du GS a provoqué une augmentation marquée des potentiels d’action sans faire changer les variables physiologiques. La technique d’enregistrement permet donc de suivre le comportement de multiples populations de neurones intrathoraciques situés dans le GS. La relation entre l’activation neuronale du GS et les changements physiologiques sont stables pour chaque chien, mais varient entre les animaux. Cela suggère que le poids relatif des boucles de rétroaction impliquées dans la régulation cardiovasculaire peut être une caractéristique propre à chaque animal. / Four micro-electrodes were inserted in the left stellate ganglion (SG) of in vivo canine preparations to evaluate the firing of neuronal somata located in this peripheral ganglion during stable cardiovascular state and following local and systemic injection of nicotine. During control periods, minor changes were observed in systolic arterial pressure, the heart rhythm and the atrioventricular conduction time. The activity generated by SG neurons remained relatively constant within each dog, but the firing rate was variable among the preparations. Systemic nicotine administration altered the physiological variables and increased the neuronal activity. Although different patterns of physiological changes were observed among the preparations, it remained invariant upon successive injections in each animal. The behaviour of the neuronal response was similar but varies in amplitude and duration both within and between the dogs. Local injections of nicotine in an artery close to the SG induced a brief and huge burst of neuronal firing, but did not influence the physiological response. The recording technique thus permit to follow the behaviour of multiple intrathoracic neuronal populations located in the SG. The relation between the SG firing and the physiological changes is stable in each dog, but differed between the animals. It suggests that the weight of the different feedback loops involved in the cardiovascular regulation might be a characteristic feature of each animal and/or the position of the electrodes in the SG is critical, since different neuronal populations are present and could react differently.

Quatre microélectrodes ont été insérées dans le ganglion stellaire gauche (GS) de préparations canines in vivo pour évaluer la décharge des potentiels d’action dans les neurones situés dans ce ganglion périphérique durant un état cardiovasculaire stable et suivant des injections systémiques et locales de nicotine. Durant les périodes de contrôle, des changements mineurs ont été observés dans la pression artérielle systolique, dans le rythme cardiaque et dans le temps de conduction atrio-ventriculaire. L’activité générée par les neurones du GS est demeurée relativement constante à l’intérieure de chaque chien, mais variait entre les préparations. L’administration de nicotine systémique a altéré les variables physiologiques et augmenté l’activité neuronale. Même si différents changements au niveau des variables physiologiques ont été observés entre les animaux, ces changements demeuraient relativement constants pour un même animal. La dynamique de la réponse neuronale était similaire, mais l’amplitude et la durée variaient entre et au sein des chiens. L’injection de nicotine dans une artère à proximité du GS a provoqué une augmentation marquée des potentiels d’action sans faire changer les variables physiologiques. La technique d’enregistrement permet donc de suivre le comportement de multiples populations de neurones intrathoraciques situés dans le GS. La relation entre l’activation neuronale du GS et les changements physiologiques sont stables pour chaque chien, mais varient entre les animaux. Cela suggère que le poids relatif des boucles de rétroaction impliquées dans la régulation cardiovasculaire peut être une caractéristique propre à chaque animal. / Four micro-electrodes were inserted in the left stellate ganglion (SG) of in vivo canine preparations to evaluate the firing of neuronal somata located in this peripheral ganglion during stable cardiovascular state and following local and systemic injection of nicotine. During control periods, minor changes were observed in systolic arterial pressure, the heart rhythm and the atrioventricular conduction time. The activity generated by SG neurons remained relatively constant within each dog, but the firing rate was variable among the preparations. Systemic nicotine administration altered the physiological variables and increased the neuronal activity. Although different patterns of physiological changes were observed among the preparations, it remained invariant upon successive injections in each animal. The behaviour of the neuronal response was similar but varies in amplitude and duration both within and between the dogs. Local injections of nicotine in an artery close to the SG induced a brief and huge burst of neuronal firing, but did not influence the physiological response. The recording technique thus permit to follow the behaviour of multiple intrathoracic neuronal populations located in the SG. The relation between the SG firing and the physiological changes is stable in each dog, but differed between the animals. It suggests that the weight of the different feedback loops involved in the cardiovascular regulation might be a characteristic feature of each animal and/or the position of the electrodes in the SG is critical, since different neuronal populations are present and could react differently.

Made available in DSpace on 2015-03-03T14:02:14Z (GMT). No. of bitstreams: 1 JussaraMCM_Tese.pdf: 1097860 bytes, checksum: 122136921e4dddbf8d0e434cbbbd3653 (MD5) Previous issue date: 2009-12-03 / The activation of hepatic stellate cells (HSC) is considered the most important event in hepatic fibrogenesis. The precise mechanism of this process is unknown in autoimmune hepatitis (AIH), and more evidence is needed on the evolution of fibrosis. The aim of this study was to assess these aspects in children with type 1 AIH. We analyzed 16 liver biopsy samples from eight patients, paired before treatment and after clinical remission, performed an immunohistochemical study with anti-actin smooth muscle antibody and graded fibrosisand inflammation on a scale of 0:4 (Batts and Ludwig scoring system). We observedthere was no significant reduction in fibrosis scores after 24? 18 months (2.5 ? 0.93 vs. 2.0? 0.53, P = 0.2012). There was an important decrease in inflammation: portal (2.6 ?0.74 vs. 1.3? 0.89, P = 0.0277), periportal/periseptal (3.0 ?0.76 vs. 1.4 ? 1.06, P = 0.0277), and lobular (2.8 ? 1.04 vs. 0.9? 0.99, P =0.0179). Anti-actin smooth muscle antibodies were expressed in the HSC of the initial biopsies (3491.93 ?2051.48 lm2), showing a significant reduction after remission (377.91 ?439.47 lm2) (P = 0.0117). HSC activation was demonstrated in the AIH of children. The reduction of this activation after clinical remission, which may precede a decrease in fibrosis, opens important perspectives in the follow-up of AIH. / A ativa??o das c?lulas hep?ticas estreladas (CHE) ? considerada o evento mais importante na fibrog?nese hep?tica. Na hepatite autoimune (HAI) este mecanismo ? desconhecido e maiores evid?ncias s?o necess?rias quanto ? evolu??o da fibrose. O objetivo desse estudo foi avaliar a ativa??o das CHE e a evolu??o da fibrose hep?tica em crian?as portadoras de HAI tipo 1. Foram analisadas 16 bi?psias hep?ticas pareadas de oito pacientes, antes do tratamento e ap?s a remiss?o cl?nica atrav?s de estudo imuno-histoqu?mico com anticorpo anti-??-actina de m?sculo liso e realizada a grada??o da fibrose e da inflama??o empregando-se o sistema de escores de Batts e Ludwig (0-4). N?o houve significante redu??o nos escores de fibrose ap?s intervalo de tempo de 24? 18 meses entre as bi?psias (2,5 ? 0,93 vs. 2,0? 0,53, P = 0,2012). Observou-se redu??o significante na inflama??o: portal (2,6?0,74 vs. 1,3? 0,89, P = 0,0277), periportal/perisseptal (3,0 ?0,76 vs. 1,4 ? 1,06, P =0,0277) e lobular (2,8 ? 1,04 vs. 0,9? 0,99, P =0,0179). A -actina de m?sculo liso nas CHE foi expressa em bi?psias hep?ticas iniciais (3491,93 ?2051,48 ?m2) e mostrou significante redu??o ap?s a remiss?o cl?nica (377,91 ?439,47 ?m2) (P = 0,0117). A ativa??o de CHE foi demonstrada em crian?as portadoras de HAI tipo 1. A redu??o de sua ativa??o ap?s remiss?o cl?nica, a qual pode preceder a redu??o da fibrose, abre importantes perspectivas no follow-up da HAI

No description available.

Le syndrome douloureux régional complexe (SDRC) est un trouble neurologique qui se caractérise par des douleurs intenses, des troubles vasomoteurs, sudomoteurs, moteurs et trophiques, accompagnés d’un œdème au niveau du membre affecté. Malgré la présence de peu de données en faveur, à cause de l’absence d’un traitement clé du SDRC, le blocage sympathique a été utilisé depuis de nombreuses années pour traiter ce syndrome. Objectif Le but principal de ce projet est d’étudier l’effet antalgique de la néostigmine utilisée comme adjuvant à la bupivacaïne lors d’un bloc stellaire dans le traitement du syndrome douloureux régional complexe du membre supérieur. Méthodes Il s’agit d’une étude pilote, randomisée en double insu. L’intensité de la douleur a été évaluée en utilisant l’échelle numérique. La force de préhension aux deux mains a été estimée par dynamométrie de Jamar. La dextérité fine des doigts a été mesurée par le « Purdue Pegboard Test ». L’œdème au niveau de la main a été déterminé par la volumétrie. Le questionnaire « SF-36 » a été utilisé afin de déterminer l’homogénéité des échantillons. Résultats Notre étude a eu des difficultés à établir l’efficacité de la thérapie par bloc stellaire dans le traitement du syndrome douloureux régional complexe. Conclusion Notre recherche n’a pu prouver l’hypothèse que le traitement de la douleur dans le SDRC du membre supérieur par un bloc stellaire est plus efficace quand l’action de l’anesthésique local est potentialisée par l’ajout de la néostigmine. / Complex regional pain syndrome (CRPS) is a neurological disorder characterized by severe pain, vasomotor, sudomotor, motor and trophic changes, accompanied by a swelling in the affected limb. Despite the limited data on his efficiency, in the absence of a definite curative treatment of the CRPS, sympathetic blocks have been used for years to treat the syndrome. Objective The main purpose of this project was to investigate the analgesic effect of neostigmine used as an adjuvant to the local anaesthetic bupivacaine in stellate ganglion blockade, in treating CRPS of the upper limb. Methods This was a pilot, randomized, double-blind study. The intensity of the pain was evaluated using a numeric scale. Grip strength in both hands was estimated by Jamar dynamometry. Fine finger dexterity was measured by the "Purdue Pegboard Test." The swelling in the hand was determined by volumetry. The questionnaire "SF-36" was used to determine the homogeneity of the samples in terms of quality of life assessment. Results Our study had difficulties in establishing the efficiency of stellate ganglion blockade in the treatment of complex regional pain syndrome. Conclusion This research project has not been able to prove that the pain treatment in upper limb CRPS by means of stellate ganglion blockade is more effective when the action of the local anesthetic is potentiated by the addition of neostigmine.

A doença de Huntington (DH) é um distúrbio neurodegenerativo hereditário e autossômico dominante e tem como características alterações motoras e mentais progressivas. Recentemente, além das alterações verificadas no sistema nervoso central, também têm sido descritas alterações em órgãos periféricos, tais como osteoporose, atrofia muscular, problemas intestinais, alterações cardíacas e, sobretudo, alterações no sistema nervoso autônomo. São evidentes as alterações autonômicas do coração nos portadores da DH, as quais, são, sobretudo, um risco potencial, tornando os pacientes suscetíveis a problemas cardiovasculares. No entanto, os mecanismos pelos quais a doença afeta os componentes autonômicos do coração não são totalmente conhecidos, por isso a importância de se estudar os componentes da inervação cardíaca, sobretudo o gânglio estrelado (GE). A DH pode ser induzida através do ácido 3-nitropropiônico (3-NP), pois essa substância produz efeitos neurotóxicos inibindo a succinato desidrogenase. Esta pesquisa objetiva analisar, por meio da indução através do 3-NP, os efeitos da DH no GE, identificando possíveis alterações morfoquantitativas dos neurônios ganglionares, com uso de técnicas baseadas em delineamento estereológico 3D e de bioimagem associadas à teste comportamental e perfil hemodinâmico, a fim de contribuir para o entendimento de como a doença age na inervação do coração. Para isso foram utilizados 14 camundongos C57BL-6 machos que foram alocados em dois grupos: Grupo Controle com 7 animais induzidos com solução salina (0,9%); Grupo 3NP com 7 animais induzidos com doses subagudas de 60 mg.kg-1dia-1 de 3-NP. Foram realizados o teste comportamental, a avaliação cardíaca e a análise estereológica. Os principais achados dessa pesquisa foram: (I) diminuição da atividade exploratória dos animais; (II) prejuízo da função sistólica; (III) aumento de 76% no volume ganglionar; (IV) aumento de 70% no volume médio dos neurônios, concluindo-se que o 3-NP produz efeitos na função cardíaca, ocasionando hipertrofia do gânglio / Huntington\'s disease (HD) is a hereditary and autosomal dominant neurodegenerative disorder and is characterized by progressive motor and mental changes. Recently, in addition to changes in the central nervous system, alterations in peripheral organs such as osteoporosis, muscular atrophy, intestinal problems, cardiac alterations and, above all, changes in the autonomic nervous system have also been described. Autonomic heart alterations in DH patients are evident, which are a potential risk, making patients susceptible to cardiovascular problems. However, the mechanisms by which the disease affects the autonomic components of the heart are not fully understood, therefore, the importance of studying the components of cardiac innervation, especially the stellate ganglion (SG). HD can be induced through 3-nitropropionic acid (3-NP), as this substance produces neurotoxic effects inhibiting succinate dehydrogenase. The aim of this research was to analyze the effects of HD on the SG by means of 3-NP induction, identifying possible morpho-quantitative changes in ganglion neurons, using techniques based on 3D stereological and bioimaging techniques associated with behavioral and hemodynamic profile, In order to contribute to the understanding of how the disease acts in the heart innervation. For this, 14 male C57BL-6 mice were used, which were allocated in two groups: Control Group with 7 animals induced with saline solution (0.9%); Group 3NP with 7 animals induced with subacute doses of 60 mg.kg-1day-1 of 3-NP. Behavioral test, cardiac evaluation and stereological analysis were performed. The main findings of this research were: (I) decrease in the exploratory activity of the animals; (II) impairment of systolic function; (III) 76% increase in ganglion volume; (IV) increase of 70% in the mean volume of the neurons, concluding that 3-NP produces effects on cardiac function, causing hypertrophy of the ganglion

O gânglio estrelado (GE) é o principal componente da inervação cardíaca extrínseca e está envolvido na gênese de diversas cardiomiopatias. Durante o envelhecimento, o controle neural do coração dos mamíferos é alterado de forma complexa e não clara, geralmente ocasionando decremento da função cardíaca e maior propensão a doenças degenerativas. A ocorrência de resultados dissonantes quanto aos parâmetros morfoquantitativos durante o envelhecimento, como o aumento ou diminuição do número total de neurônios simpáticos, é assunto para discussões interessantes. Esta pesquisa foi conduzida em preás machos (Galea spixii), um pequeno roedor da fauna brasileira. Desta forma, estudou-se o efeito do desenvolvimento pós-natal (maturação e envelhecimento) na macro e microestrutura do gânglio estrelado esquerdo (GEe) de preás, por meio de microscopia quantitativa tridimensional (Estereologia) associada a técnicas de imuno-histoquímica. De acordo com a fase específica do desenvolvimento pós-natal, os animais foram alocados nos seguintes grupos etários: Neonatos, Jovens, Adultos e Senis. Inicialmente, os animais foram submetidos à eutanásia e seus gânglios estrelados esquerdos coletados e fixados em solução de formaldeído (4%) em PBS. Foi realizada amostragem sistemática e uniformemente aleatória (SURS), estimando-se: volume do GEe, volume neuronal e número total de neurônios do GEe. Os principais achados deste estudo foram: i) aumento do comprimento do gânglio - 42% entre Neonato e Senil; 34% entre Jovem e Senil e 35% entre Adulto e Senil; ii) hipertrofia do GEe - 171% entre os grupos Neonato e Adulto; iii) aumento do tecido não neuronal - 268% entre os grupos Neonato e Adulto; iv) estabilidade no número total de neurônios uninucleados, binucleados e total (uni+bi); v) estabilidade no tamanho (volume) dos neurônios uninucleados e binucleados; e vi) estabilidade no número total de neurônios imunorreativos ao Ki-67 (uni+bi). Espera-se que os resultados gerados por esta pesquisa possam esclarecer alguns aspectos estruturais da plasticidade neural durante o desenvolvimento pós-natal de preás, avançando assim o conhecimento acerca da inervação cardíaca extrínseca / The stellate ganglion (SG) is a main component of extrinsic cardiac innervation and is involved in the genesis of various cardiomyopathies. During ageing, the neural control of heart in mammals is altered in the complex shape and unclear, generally cause decrement in the cardiac function and a greater propensity to degenerative diseases. The occurrence of discordant results regarding the morphoquantitative parameters during ageing, such as increase or decrease in the total number of sympathetic neurons, is a subject for interesting discussions. This research was conducted in males preas (Galea spixii), a small rodent of the Brazilian fauna. Therefore, this work aimed to study the effect of postnatal development (maturation and ageing) in the macro and microstructure of the left stellate ganglion (LSG) in preas by dimensional quantitative microscopy (Stereology) associated to immunohistochemistry techniques. According to a specific stage of postnatal development, the animals were allocated into the following age groups: Newborn, Young, Adult and Elderly. The animals were euthanised and the left stellate ganglia were collected and fixed in 4% formaldehyde solution in PBS. A systematic uniformly random sampling (SURS) was performed to estimate: the volume of LSG, neuron volume and the total number of LSG neurons. The main findings of this study were: i) increase in length ganglia - 42% between Newborn and Elderly; 34% between Young and Elderly and 35% between Adult and Elderly; ii) hypertrophy of LSG - 171% between the groups Newborn and Adult; iii) increase of non-neuronal tissue - 268% between the groups Newborn and Adult; iv) stability for the total number of uninucleate neurons, binucleate neurons and total (uni+bi); v) stability in the size (volume) of uninucleate and binucleate neurons; and, vi) stability for the total number of neurons immunorreactive to Ki-67 (uni+bi). It is expected that the results generated for this research may clarify structural aspects of neural plasticity during the postnatal development of preas, thus advancing the knowledge about the extrinsic cardiac innervation

A fibrose hepática resulta da cronicidade da injúria celular, ocasionando acúmulo dos componentes da matriz extracelular (MEC) pela ativação, principalmente, de células estreladas e fibroblastos portais em miofibroblastos. Estas células se conectam através de junções comunicantes do tipo gap, formadas por proteínas denominadas conexinas (Cx). As junções gap são responsáveis pelo fluxo de moléculas e íons entre as células, desempenhando importante função no controle da homeostasia tecidual. Diversos tipos de conexinas foram descritas nas células hepáticas. Os hepatócitos expressam Cx32 e Cx26, enquanto as demais células não-parenquimatosas expressam Cx43. Alguns estudos analisaram a expressão das conexinas e das junções gap em processos de reparação e fibrogênese em diferentes tecidos, no entanto, poucos avaliaram seu papel na fibrogênese hepática. Sendo assim, o objetivo deste estudo foi avaliar os aspectos morfológicos, histopatológicos e moleculares da fibrose hepática, induzida por tetracloreto de carbono (CCl4), em animais deficientes para as conexinas 43 (Cx43+/-) ou 32 (Cx32-/-). Foram analisados dados biométricos, histopatológicos, ultra-estruturais, imuno-histoquímicos e bioquímicos, além da expressão gênica e protéica das conexinas. Os aspectos moleculares da fibrose hepática foram analisados pela expressão de genes relacionados com a deposição e degradação da matriz extracelular por PCR em tempo real. As análises macroscópicas e de varredura demonstraram um processo de micronodulação da superfície hepática mais acentuado nos camundongos Cx43+/- fibróticos em relação aos animais wild-type (Cx43+/+) fibróticos. Adicionalmente, estes animais apresentaram maior proporção volumétrica de colágeno no tecido hepático; redução na atividade necroinflamatória tecidual; redução nas concentrações séricas de AST e ALT; redução na proliferação celular dos hepatócitos e redução na expressão dos genes: colágeno tipo I, TGFβ-1, MMP-2, MMP-13 e TIMP-1. Por sua vez, os camundongos Cx32-/- fibróticos apresentaram aumento na deposição de colágeno no parênquima hepático; aumento na atividade necroinflamatória tecidual e aumento nos níveis séricos das enzimas hepáticas AST, ALT e fosfatase alcalina em comparação aos animais wild-type (Cx32+/+) fibróticos. Também foram observadas redução na proliferação hepatocelular e maior quantidade de corpúsculos apoptóticos no tecido hepático. Baseando-se em todos os resultados obtidos, observou-se que ambos os modelos animais apresentaram aumento da fibrose hepática, aparentemente ocasionada por diferentes modos de ação. Os animais deficientes em Cx43 apresentaram menor capacidade de degradação do colágeno, ocasionando seu acúmulo no tecido hepático. Por outro lado, os animais deficientes em Cx32 apresentaram maior deposição de colágeno em resposta à injúria hepatocelular mais acentuada, aliada ao desequilíbrio entre as taxas de proliferação celular e apoptose. Em conclusão, os resultados obtidos neste trabalho demonstraram a importante participação das conexinas no controle da fibrogênese hepática, e que podem representar potenciais alvos terapêuticos para o tratamento das doenças hepáticas crônicas em humanos e animais. / Hepatic fibrosis results from chronic cell injury, leading to accumulation of components of extracellular matrix (ECM) through activation mainly of hepatic stellate cells and portal fibroblasts into myofibroblasts. These cells communicate through intercellular gap junctions composed of proteins known as connexins (Cx). Gap junctions are responsible for the exchange of molecules and ions among cells, playing an important role in the control of tissue homeostasis. Several subtypes of connexins were described among hepatic cells. Hepatocytes express Cx32 and Cx26, while the other non-parenchymal cells express Cx43. Some studies analyzed the expression of connexins and gap junctions on processes of healing and fibrogenesis in different tissues; however, few studies evaluated its role on hepatic fibrogenesis. Thus, the objective of this study was to evaluate morphological, histopathological and molecular aspects of hepatic fibrosis induced by carbon tetrachloride (CCl4) in animals with connexin 43 (Cx43+/-) or 32 (Cx32-/-) deficiency. We analyzed biometric, histopathological, ultrastructural, immunohistochemical and biochemical data, besides gene and protein expression of connexins. Molecular aspects of hepatic fibrosis were analyzed with the expression of genes related to deposition and degradation of extracellular matrix by real time PCR. Macroscopic and Scanning Electron Microscopy analyses showed a process of micronodulation of hepatic surface more accentuated on Cx43+/- fibrotic mice when compared to fibrotic wild-type (Cx43+/+) animals. Additionally, these animals presented a higher collagen volumetric proportion on hepatic tissue; reduction of tissue necroinflammatory activity; reduction of serum AST and ALT; reduction of hepatocytes proliferation and reduction of expression type I collagen, TGFβ-1, MMP-2, MMP-13 and TIMP-1 genes. Fibrotic Cx32-/- mice presented an increase of collagen deposition in hepatic parenchyma; increase of tissue necro-inflammatory activity and increase of liver enzymes AST, ALT and alkaline phosphatase when compared to fibrotic wild-type (Cx32+/+) animals. Reduction of hepatocellular proliferation and a higher amount of apoptotic bodies on hepatic tissue were also observed. Based on the results obtained, we observed that both animal models showed an increase of hepatic fibrosis, apparently caused by different modes of action. Cx43 deficient animals showed a reduced capacity to degrade collagen, causing its accumulation in the hepatic tissue. Cx32 deficient animals showed an increased collagen deposition in response to accentuated hepatocellular injury, together to an unbalance between rates of cellular proliferation and apoptosis. In conclusion, results obtained on this study demonstrate an important role of connexins on the control of hepatic fibrogenesis, which could represent potential therapeutical targets for the treatment of chronic liver diseases in humans and animals.

A fibrose hepática resulta da cronicidade da injúria celular, ocasionando acúmulo dos componentes da matriz extracelular (MEC) pela ativação, principalmente, de células estreladas e fibroblastos portais em miofibroblastos. Estas células se conectam através de junções comunicantes do tipo gap, formadas por proteínas denominadas conexinas (Cx). As junções gap são responsáveis pelo fluxo de moléculas e íons entre as células, desempenhando importante função no controle da homeostasia tecidual. Diversos tipos de conexinas foram descritas nas células hepáticas. Os hepatócitos expressam Cx32 e Cx26, enquanto as demais células não-parenquimatosas expressam Cx43. Alguns estudos analisaram a expressão das conexinas e das junções gap em processos de reparação e fibrogênese em diferentes tecidos, no entanto, poucos avaliaram seu papel na fibrogênese hepática. Sendo assim, o objetivo deste estudo foi avaliar os aspectos morfológicos, histopatológicos e moleculares da fibrose hepática, induzida por tetracloreto de carbono (CCl4), em animais deficientes para as conexinas 43 (Cx43+/-) ou 32 (Cx32-/-). Foram analisados dados biométricos, histopatológicos, ultra-estruturais, imuno-histoquímicos e bioquímicos, além da expressão gênica e protéica das conexinas. Os aspectos moleculares da fibrose hepática foram analisados pela expressão de genes relacionados com a deposição e degradação da matriz extracelular por PCR em tempo real. As análises macroscópicas e de varredura demonstraram um processo de micronodulação da superfície hepática mais acentuado nos camundongos Cx43+/- fibróticos em relação aos animais wild-type (Cx43+/+) fibróticos. Adicionalmente, estes animais apresentaram maior proporção volumétrica de colágeno no tecido hepático; redução na atividade necroinflamatória tecidual; redução nas concentrações séricas de AST e ALT; redução na proliferação celular dos hepatócitos e redução na expressão dos genes: colágeno tipo I, TGFβ-1, MMP-2, MMP-13 e TIMP-1. Por sua vez, os camundongos Cx32-/- fibróticos apresentaram aumento na deposição de colágeno no parênquima hepático; aumento na atividade necroinflamatória tecidual e aumento nos níveis séricos das enzimas hepáticas AST, ALT e fosfatase alcalina em comparação aos animais wild-type (Cx32+/+) fibróticos. Também foram observadas redução na proliferação hepatocelular e maior quantidade de corpúsculos apoptóticos no tecido hepático. Baseando-se em todos os resultados obtidos, observou-se que ambos os modelos animais apresentaram aumento da fibrose hepática, aparentemente ocasionada por diferentes modos de ação. Os animais deficientes em Cx43 apresentaram menor capacidade de degradação do colágeno, ocasionando seu acúmulo no tecido hepático. Por outro lado, os animais deficientes em Cx32 apresentaram maior deposição de colágeno em resposta à injúria hepatocelular mais acentuada, aliada ao desequilíbrio entre as taxas de proliferação celular e apoptose. Em conclusão, os resultados obtidos neste trabalho demonstraram a importante participação das conexinas no controle da fibrogênese hepática, e que podem representar potenciais alvos terapêuticos para o tratamento das doenças hepáticas crônicas em humanos e animais. / Hepatic fibrosis results from chronic cell injury, leading to accumulation of components of extracellular matrix (ECM) through activation mainly of hepatic stellate cells and portal fibroblasts into myofibroblasts. These cells communicate through intercellular gap junctions composed of proteins known as connexins (Cx). Gap junctions are responsible for the exchange of molecules and ions among cells, playing an important role in the control of tissue homeostasis. Several subtypes of connexins were described among hepatic cells. Hepatocytes express Cx32 and Cx26, while the other non-parenchymal cells express Cx43. Some studies analyzed the expression of connexins and gap junctions on processes of healing and fibrogenesis in different tissues; however, few studies evaluated its role on hepatic fibrogenesis. Thus, the objective of this study was to evaluate morphological, histopathological and molecular aspects of hepatic fibrosis induced by carbon tetrachloride (CCl4) in animals with connexin 43 (Cx43+/-) or 32 (Cx32-/-) deficiency. We analyzed biometric, histopathological, ultrastructural, immunohistochemical and biochemical data, besides gene and protein expression of connexins. Molecular aspects of hepatic fibrosis were analyzed with the expression of genes related to deposition and degradation of extracellular matrix by real time PCR. Macroscopic and Scanning Electron Microscopy analyses showed a process of micronodulation of hepatic surface more accentuated on Cx43+/- fibrotic mice when compared to fibrotic wild-type (Cx43+/+) animals. Additionally, these animals presented a higher collagen volumetric proportion on hepatic tissue; reduction of tissue necroinflammatory activity; reduction of serum AST and ALT; reduction of hepatocytes proliferation and reduction of expression type I collagen, TGFβ-1, MMP-2, MMP-13 and TIMP-1 genes. Fibrotic Cx32-/- mice presented an increase of collagen deposition in hepatic parenchyma; increase of tissue necro-inflammatory activity and increase of liver enzymes AST, ALT and alkaline phosphatase when compared to fibrotic wild-type (Cx32+/+) animals. Reduction of hepatocellular proliferation and a higher amount of apoptotic bodies on hepatic tissue were also observed. Based on the results obtained, we observed that both animal models showed an increase of hepatic fibrosis, apparently caused by different modes of action. Cx43 deficient animals showed a reduced capacity to degrade collagen, causing its accumulation in the hepatic tissue. Cx32 deficient animals showed an increased collagen deposition in response to accentuated hepatocellular injury, together to an unbalance between rates of cellular proliferation and apoptosis. In conclusion, results obtained on this study demonstrate an important role of connexins on the control of hepatic fibrogenesis, which could represent potential therapeutical targets for the treatment of chronic liver diseases in humans and animals.