莱菔子水溶性生物碱对ApoE^-/-小鼠血管内皮保护机制的实验研究

【作者】 张国侠；

【导师】 盖国忠；

【作者基本信息】 长春中医药大学 ， 中医内科学， 2010， 博士

【摘要】 动脉粥样硬化是导致心、脑血管疾病的主要发生和死亡原因。动脉粥样硬化的特点是动脉粥样硬化的存在,导致动脉的血管腔内膜狭窄。动脉粥样硬化的危险因素包括低密度脂蛋白胆固醇水平升高,高密度脂蛋白胆固醇水平降低,甘油三酯水平升高,肥胖,高血压,吸烟,糖尿病,和遗传因素等。其发病涉及体内脂代谢的紊乱和血管内皮功能障碍等方面,由于其发病的分子机制较多,故在治疗上单一靶点的治疗不如多靶点的协同作用。因此,寻求有效中医药治疗途径,发挥中医药整体调节优势有着十分重要的意义。导师盖国忠教授认为本病的病机关键为本虚标实,“痰浊壅滞”是最主要的致病因素,临床应用莱菔子抗动脉粥样硬化相关性疾病,取其降气化痰、通腑泻浊之功效,疗效满意。为进一步阐明莱菔子的抗动脉粥样硬化作用及相关机制,予以客观的、科学的论证。本研究提取了莱菔子有效成分水溶性生物碱,并以ApoE-/-小鼠为研究对象,进行了以下几方面的研究:1.莱菔子水溶性生物碱对ApoE-/-小鼠血脂的影响;2.莱菔子水溶性生物碱对ApoE-/-小鼠血清一氧化氮(NO)、一氧化氮合酶(NOS)的影响;3.莱菔子水溶性生物碱对ApoE-/-小鼠血清超氧化物歧化酶(SOD)、丙二醛(MDA)含量的影响;4.莱菔子水溶性生物碱对ApoE-/-小鼠胸主动脉核因子-κB(NF-κB)含量、胸主动脉内皮一氧化氮合酶(eNOS)含量、胸主动脉内皮eNOS mRNA表达的影响。实验结果显示:1.莱菔子水溶性生物碱能够降低ApoE-/-小鼠血清甘油三酯、总胆固醇、低密度脂蛋白胆固醇含量,提高高密度脂蛋白胆固醇含量;2.能够调节ApoE-/-小鼠血管活性物质生成和释放,升高血清NO含量,提高血清NOS的活性;3.具有抗氧化作用,能够提高ApoE-/-小鼠血清SOD活性,降低MDA含量;4.能够抑制ApoE-/-小鼠胸主动脉NF-κB的蛋白表达;增加胸主动脉eNOS蛋白表达,增加胸主动脉eNOSmRNA表达,具有保护内皮细胞功能的作用。通过本课题的研究,从调节血脂和激活NO-NOS系统对莱菔子的作用机制进行了探讨,为临床应用莱菔子治疗动脉粥样硬化提供了客观依据。更多还原

【Abstract】 Cardiovascular or Brain disease due to atherosclerosis is the major cause of mortality and morbidity. Atherosclerosis is characterized by the presence of atherosclerosis, leading to artery intima lumen stenosis. Risk factors of atherosclerosis include elevated low-density lipoprotein-cholesterol levels, low high-density lipoprotein-cholesterol levels, elevated TG levels, obesity, hypertension, smoking, diabetes, and genetic factors,et al. The incidence of the disorder related to lipid metabolism in vivo and vascular endothelial dysfunction in such areas, Because of its molecular mechanism of disease are more so on a single target in the treatment than the treatment of multi-target synergy. Therefore, the search for effective therapeutic approach of Chinese medicine, which plays a great significance to regulate advantage.Tutor guo zhong gai Professor thought the key of this disease is ben xv biao shi, The most important pathogenic factors is tan zhuo yong zhi, Radish Seed clinical application of anti-atherosclerosis reach good effect.and it can play jiang qi hua tan,tong fu xie zhuo role. To further clarify the anti-atherosclerosis effect and related mechanisms of Radish Seed, prove objective, scientific evaluation, We extract the active ingredients of the Radish Seed,which is soluble semen raphani alkaloids,And used ApoE knockout (ApoE-/-) mice for the study, carried out the following studies:1. Soluble semen raphani alkaloids effects on the ApoE-/- mice with plasma lipid levels;2. Soluble semen raphani alkaloids effects on the serum nitric oxide (NO), nitric oxide synthase (NOS) ;3. Soluble semen raphani alkaloids effects on the ApoE-/- mouse serum superoxide dismutase (SOD), malondialdehyde (MDA) content of impact;4. Soluble semen raphani alkaloids effects on the ApoE-/- mice aorta of nuclear factor-κB (NF-κB) content of aortic endothelial nitric oxide synthase (eNOS) content in thoracic aorta endothelial nitric oxide synthase (eNOS) mRNA expression in impact.The results showed that:1. Soluble semen raphani alkaloids could reduce the ApoE-/- mice with serum triglyceride, total cholesterol, low-density lipoprotein cholesterol, increased high-density lipoprotein cholesterol;2. Soluble semen raphani alkaloids could regulate ApoE-/- mice production and release of vasoactive substances, elevated serum NO content and NOS activity increased serum;3. Soluble semen raphani alkaloids could anti-oxidation, improve the ApoE-/- mice serum SOD activity and lower MDA content;4. Soluble semen raphani alkaloids could inhibit the ApoE-/- mice with aortic protein expression of NF-κB; increase in aortic eNOS protein expression, increasing thoracic aorta eNOSmRNA expression of a protective role in endothelial cell function.Through the research projects, from regulating blood lipids and activation of NO-NOS system on Radish Seed mechanism of action was discussed for the clinical application of Radish Seed treatment of atherosclerosis to provide an objective basis.更多还原