Endothelial dysfunction (ED) is associated with many cardiovascular conditions including hypertension and hyperhomocysteinemia. The decreased bioavailability of nitric oxide and increased oxidative stress are the hallmarks of ED. Apart from the mainstream Western medicine treatment, Chinese medical interventions have also demonstrated their capacity in dealing with a great variety of cardiovascular conditions. The effectiveness of acupuncture on hypertension has been recognized by the World Health Organization but the underlying mechanisms have hitherto remained largely obscure. A commonly prescribed Chinese herb, the Root of Rhodiola rosea has been used to treatment a wide range of cardiovascular conditions but its effect on ED is also unclear. In this thesis, we have explored the effects and the underlying mechanism of these two important Chinese medical interventions. / In the first part, we have performed an acupuncture study on hypertensive animals. Eighteen weeks old adult Wistor Kyoto Rats (WKYs) and Spontaneously Hypertensive Rats (SHRs) were divided into WKY control, SHR control, Sham-acupuncture and real acupuncture groups. Electroacupuncture was performed on acupoints ST36 and LR3 in the real acupuncture group for 6 weeks. The blood pressure at the end of the treatment was lowered in acupuncture group when compared with SHR control and sham-acupuncture group. Serum angiotensin II level in SHR controls was higher than that in WKY control and acupuncture treatment significantly attenuated it. Dihydroethidium (DHE) imaging showed that the reactive oxygen species (ROS) level was reduced in the aortas and carotid arteries of acupuncture treated SHR. Biochemical assays showed that acupuncture inhibited the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and enhanced antioxidant capacity. In functional studies, the endothelial dependent relaxation of aorta rings and carotid arteries to acetylcholine were improved in acupuncture group. SHRs received acupuncture also expressed a elevation of eNOS and peNOS level and inhibition of nitrotyrosine level in Western blotting assay. The nitrate/nitrite level in aortic tissue was also increased by acupuncture. The findings concluded that one of the possible mechanisms of acupuncture in lowering blood pressure involved the improvement of oxidative stress, nitric oxide bioavailability and endothelium functions. / In the second part, we have studied the effects of salidroside, an active ingredient of the root of Rhodiola rosea with documented antioxidative, antihypoxia and neuroprotective properties on homocysteine induced ED. Functional studies on the rat aortas were performed to delineate the vascular effect of salidroside. Exposure to homocysteine attenuated endothelium-dependent relaxations in rat aortas while salidroside pretreatment rescued it. DHE imaging revealed that salidroside inhibited homocysteine-induced elevation in ROS production in both aortas and cultured endothelial cells. Western blot analysis showed that salidroside increased the phosphorylation of eNOS which was diminished by homocysteine in endothelial cells. Moreover, salidroside inhibited the NOX2 expression which was promoted by homocysteine in aorta tissue. The findings suggested that salidroside was effective in preserving the NO bioavailability and reducing ROS level, thereby protecting against homocysteine-induced impairment of ED. / We have successfully demonstrated the two Chinese medicine modalities, i.e. acupuncture and salidroside, a naturally occurring chemical compound isolated from Rhodiola rosea, delivered beneficial effects on ED, and both of them exert anti-oxidative effects for their action. Our experimental findings have enhanced the prospective of using Chinese medical interventions to manage oxidative stress-associated cardiovascular conditions and also helped put the clinical use of Chinese medical interventions on a more scientific footing. / 內皮功能失調與很多心血管系統疾病，包括高血壓和高半胱氨酸過高症有著十分密切的關系，一氧化氮供應減少與氧化應激增加均為這病理現象的一個特徵。除了主流的西方醫學治療方法外，中醫藥也一直表現出對各種心血管系統疾病有著明顯的療效。其中以針灸治療高血壓雖然己被世界衛生組織認可為一有效之療法，然而其療效原理卻並未被完全了解。另外，中草藥當中的紅景天，其對心血管疾病的療效亦非常顯著，唯其對內皮功能失調之影響卻仍有待查証。在這部論文當中，作者將會對以上兩項中醫藥治療方法的原理作出深入探討。 / 在第一部份的實驗當中，作者對自發性高血壓的大鼠施行了針灸治療。把十八週歲的自發性高血壓大鼠與京都種大鼠分為1)京都種大鼠對照組 2)自發性高血壓大鼠對照組 3)假針組針針刺組。針刺組中所使用的方案乃於足三里和太沖施行為期六週的電針治療。治療後針刺組的血壓相對於高血壓大鼠對照組和假針組均有明顯下降。同時針刺組大鼠血液中的血管緊張素II亦明顯降低。顯微鏡螢光造影發現於主動脈與頸動脈組織中，超氧化因子數量於針刺後均低於另外兩組高血壓大鼠對照組與假針組。另外實驗結果亦發現尼克酰胺腺嘌呤二核苷酸磷酸氧化酶的活動於針刺後下降，而抗氧化總容量則有所提升。另一方面，血管功能測試則顯示在針刺組內，由乙酰胆碱所引發的血管舒張比對照所產生的有所增加。而內皮一氧化氮酶和磷化皮內皮一氧化氮酶於血管中的表達則於針刺治療後有所增加，反觀硝基酪氨酸的含量則於針刺後減少。針刺對於血管組織中的亚硝酸盐/硝酸盐含量均有刺激作用。綜合而言，針刺能透過抑制氧化應激從而增加血管中一氧化氮的含量，最後達至內皮功能改善而降低血壓。 / 在第二部份，作者對中藥紅景天內其中一種活性成份紅景天苷對半胱氨酸所引起的內皮功能損傷進行研究。血管功能測試顯示半胱氨酸抑制了由乙酰胆碱所引發的血管舒張，而紅景天苷則能有效逆轉該抑制作用。顯微鏡螢光造影則發現紅景天苷能壓制由半胱氨酸所刺激的超氧化因子，另一方面能增加由半胱氨酸所抑制的磷化皮內皮一氧化氮酶的表達。尼克酰胺腺嘌呤二核苷酸磷酸氧化酶為超氧化因子的其中一個主要來源，半胱氨酸被發現會對其當中NOX2亞組的表達有刺激作用，而紅景天苷則能減少其表達。實驗結果顯示紅景天苷對半胱氨酸所引起的內皮功能損傷有顯著保護作用，其原理則與減少氧化因子從而增加一氧化氮的含量有密切關系。 / 整體而言，本論文成功顯示針灸與紅景天苷兩項中醫藥治療方案均能夠透過抑制超氧化因子而改善內皮功能捐傷。實驗結果加強了中醫藥於治療氧化應激相關的心血管疾病的應用，為中醫藥發展提供堅實的科學基礎。 / Leung, Sin Bond. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2014. / Includes bibliographical references. / Abstracts also in Chinese. / Title from PDF title page (viewed on 01, November, 2016). / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only.
| Identifer | oai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_1290672 |
| Date | January 2014 |
| Contributors | Leung, Sin Bond (author.), Lin, Zhixiu (thesis advisor.), Chinese University of Hong Kong Graduate School. Division of Chinese Medicine. (degree granting institution.) |
| Source Sets | The Chinese University of Hong Kong |
| Language | English, Chinese |
| Detected Language | English |
| Type | Text, bibliography, text |
| Format | electronic resource, electronic resource, remote, 1 online resource (xxv, 224 leaves) : illustrations, computer, online resource |
| Rights | Use of this resource is governed by the terms and conditions of the Creative Commons "Attribution-NonCommercial-NoDerivatives 4.0 International" License (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
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