La drépanocytose résulte d’une mutation du gène β-globine entrainant la synthèse d’une hémoglobine anormale, l’HBS, qui polymérise en condition désoxygénée. Le globule rouge deviendra plus rigide et plus fragile, donnant lieu a deux conséquences majeures : l’hémolyse accrue et l’occlusion vasculaire.Récemment, un nouvel acteur moléculaire, l’adénosine, a été identifie. Ce nucléoside présente des effets bénéfiques sur les atteintes pulmonaires en inhibant l’activation des cellules « tueur naturel t inductibles », mais aussi délétères en favorisant la polymérisation de l’HBS et la survenue du priapisme, une des complications drépanocytaires.Les travaux menés ont pour objectifs d’étudier les effets délétères potentiels de l’adénosine, à travers l’étude de l’implication des enzymes de la voie métabolique de l’adénosine dans l’hémolyse ainsi que dans la survenue du priapisme chez des patients drépanocytaires. Pour ce faire, une cohorte composée d’adultes et d’enfants SS a été étudiée. Les résultats obtenus ont permis de préciser le rôle du métabolisme de l’adénosine dans les mécanismes physiopathologiques de la drépanocytose. Nos résultats n’ont pas permis de mettre en évidence de différence d’expression (ARN, protéine) des enzymes du métabolisme de l’adénosine entre les patients présentant des antécédents priapiques et ceux indemnes de cette complication. Néanmoins, nos recherches ont permis d’identifier l’adénylate cyclasse 6 comme gène modulateur de l’hémolyse et d’apporter de nouveaux éléments en accord avec la classification du priapisme comme appartenant au sous-phénotype hyperhémolytique à travers notamment l’étude des caractéristiques hemorhéologiques. / Sickle-cell disease is caused by a mutation in the β-globin gene leading to an abnormal hemoglobin, hbs. This change allows polymerization of HBS when deoxygenated. Erythrocytes become more rigid and fragile, leading to the two major manifestations of the disease: hemolysis and vaso-occlusion.Recently, adenosine has been identified as a new molecular actor of this disease. This nucleoside may have beneficial effects by preventing inkt cells activation and pulmonary inflammation. But it may also exhibit deleterious effects by activing a signalling pathway leading to erythrocyte sickling and the occurrence of priapism, a sickle cell disease complication.The purpose of our work, based on the potential deleterious effects induced by adenosine was to precise the involvement of adenosine metabolic pathway enzymes in hemolysis and the occurrence of priapism. Two cohorts of children and adult ss patients and men ss have been studied respectively.Our results had clarified the role of metabolism of adenosine in the pathophysiological mechanisms of sickle cell disease. Our results did not allow detecting evidence of differential expression (rna, protein levels) of adenosine metabolism enzymes between ss adult patients exhibiting priapic events and those who had never experienced this complication. Nevertheless, our work has led to the identification of adenylate cyclase as modifier gene of hemolysis and has bring new elements on the priapism classification to the hyper hemolytic sub-phenotype with the description of the hemorheological features associated with this complication.

O objetivo do presente trabalho é avaliar através de métodos quantitativos e qualitativos, as alterações nos corpos cavernosos de indivíduos com priapismo isquêmico. Foram estudados fragmentos de corpos cavernosos obtidos por biópsia de sete pacientes com, pelo menos, 48 horas de priapismo isquêmico, com idade entre 27 e 44 anos (média de 38 anos). Os pacientes foram submetidos a tratamento cirúrgico pela técnica de Al-ghorab. O material foi submetido a técnicas histoquímicas e imunohistoquímicas para a caracterização e quantificação do músculo liso e dos elementos fibrosos do tecido conjuntivo. A análise do corpo cavernoso dos pacientes com priapismo e do grupo controle, mostrou os seguintes resultados: Colágeno: controle = 34.76 4.64, priapismo = 39.64 2.91 (p = 0.0019); sistema elástico: controle 28.10 2.85, priapismo 36.10 3.06 (p = 0.0012) fibras musculares: controle = 43.37 4.96, priapismo = 26.48 5.00 (p < 0.0001). Ficou caracterizado aumento estatisticamente significativo dos elementos fibrosos do tecido conjuntivo e diminuição significativa nas fibras musculares lisas do corpo cavernoso dos pacientes com priapismo isquêmico. O presente estudo mostrou que o priapismo isquêmico está associado a alterações significativas nos componentes da matriz extracelular e na musculatura lisa do corpo cavernoso. Esses resultados poderiam explicar a disfunção erétil que acompanha os pacientes com priapismo isquêmico. / The purpose of the present study was to evaluate through quantitative and qualitative methods, the changes in the corpora cavernosa of patients with ischemic priapism. We obtained samples of corpora cavernosa from 7 patients with ischemic priapism, aged between 28 and 44 years (mean = 38), who underwent a cavernosal-glandular shunt. The control tissues were fragments of corpora cavernosa obtained from autopsies of 7 age-matched men who died of causes not related to the urogenital tract. Histochemical and immunohistochemical techniques were used to assess and quantify the extra-cellular matrix and smooth muscle fibers. The volumetric density of smooth muscle, elastic fibers and collagen were determined in corpora cavernosa. The stereological analysis showed the following values of volumetric density in the structures studied. Collagen: controls = 34.76 4.64, priapism = 39.64 2.91 (p = 0.0019); elastic system fibers: controls 28.10 2.85, priapism 36.10 3.06 (p = 0.0012), smooth muscle fibers: controls = 43.37 4.96, priapism = 26.48 5.00 (p < 0.0001). Our results demonstrated a significant increase in the fibrous elements of the connective tissue and a significant decrease of smooth muscle fibers in the corpora cavernosa of patients with ischemic priapism, when compared to controls. As conclusion, this study showed that ischemic priapism is associated with early significant changes in the components of the extra cellular matrix and smooth muscle fibers of corpora cavernosa. This could explain the frequent occurrence of erectile dysfunction found in patients with ischemic priapism.

O objetivo do presente trabalho é avaliar através de métodos quantitativos e qualitativos, as alterações nos corpos cavernosos de indivíduos com priapismo isquêmico. Foram estudados fragmentos de corpos cavernosos obtidos por biópsia de sete pacientes com, pelo menos, 48 horas de priapismo isquêmico, com idade entre 27 e 44 anos (média de 38 anos). Os pacientes foram submetidos a tratamento cirúrgico pela técnica de Al-ghorab. O material foi submetido a técnicas histoquímicas e imunohistoquímicas para a caracterização e quantificação do músculo liso e dos elementos fibrosos do tecido conjuntivo. A análise do corpo cavernoso dos pacientes com priapismo e do grupo controle, mostrou os seguintes resultados: Colágeno: controle = 34.76 4.64, priapismo = 39.64 2.91 (p = 0.0019); sistema elástico: controle 28.10 2.85, priapismo 36.10 3.06 (p = 0.0012) fibras musculares: controle = 43.37 4.96, priapismo = 26.48 5.00 (p < 0.0001). Ficou caracterizado aumento estatisticamente significativo dos elementos fibrosos do tecido conjuntivo e diminuição significativa nas fibras musculares lisas do corpo cavernoso dos pacientes com priapismo isquêmico. O presente estudo mostrou que o priapismo isquêmico está associado a alterações significativas nos componentes da matriz extracelular e na musculatura lisa do corpo cavernoso. Esses resultados poderiam explicar a disfunção erétil que acompanha os pacientes com priapismo isquêmico. / The purpose of the present study was to evaluate through quantitative and qualitative methods, the changes in the corpora cavernosa of patients with ischemic priapism. We obtained samples of corpora cavernosa from 7 patients with ischemic priapism, aged between 28 and 44 years (mean = 38), who underwent a cavernosal-glandular shunt. The control tissues were fragments of corpora cavernosa obtained from autopsies of 7 age-matched men who died of causes not related to the urogenital tract. Histochemical and immunohistochemical techniques were used to assess and quantify the extra-cellular matrix and smooth muscle fibers. The volumetric density of smooth muscle, elastic fibers and collagen were determined in corpora cavernosa. The stereological analysis showed the following values of volumetric density in the structures studied. Collagen: controls = 34.76 4.64, priapism = 39.64 2.91 (p = 0.0019); elastic system fibers: controls 28.10 2.85, priapism 36.10 3.06 (p = 0.0012), smooth muscle fibers: controls = 43.37 4.96, priapism = 26.48 5.00 (p < 0.0001). Our results demonstrated a significant increase in the fibrous elements of the connective tissue and a significant decrease of smooth muscle fibers in the corpora cavernosa of patients with ischemic priapism, when compared to controls. As conclusion, this study showed that ischemic priapism is associated with early significant changes in the components of the extra cellular matrix and smooth muscle fibers of corpora cavernosa. This could explain the frequent occurrence of erectile dysfunction found in patients with ischemic priapism.