【作者】 高泓；

【导师】 谢春光；

【作者基本信息】 成都中医药大学 ， 中医内科学， 2009， 博士

【摘要】 目的：通过观察具有养阴益气活血功效的参芪复方对糖尿病大血管病变的防治作用,从整体水平、细胞水平、分子水平评价参芪复方对糖尿病大血管GK大鼠的作用效果,由细胞信号转导的角度阐释参芪复方防治糖尿病并发大血管病变对于主动脉PI3-K／Akt通路的影响,为中医药防治糖尿病大血管病变的治疗机制、机体的反应机制做出相应研究。方法：73只GK大鼠随机分为4组：GK组18只、模型组19只、西药阿托伐他汀组18只、中药参芪复方组18只,Wistar大鼠18只作为正常Wistar对照组。模型、西药、中药组给予eNOS抑制剂L-NAME 0.1mg·ml-1·d-1,加入饮用水中进行糖尿病大血管病变造模,造模时间为35天。造模同时开始给药,Wistar组喂饲普通饲料,其余各组喂饲高脂饲料。正常Wistar对照组按5ml·kg-1·d-1灌服生理盐水,GK组按5ml·kg-1·d-1灌服生理盐水,模型组按5ml·kg-1·d-1灌服生理盐水,西药阿托伐他汀组按1.6mg·kg-1·d-1灌服阿托伐他汀钙悬液,中药参芪复方组按1.44g·kg-1·d-1灌服参芪复方混悬液。35天后处死大鼠,检测各组血糖、血脂、血清CRP、INS水平,并利用实时荧光定量PCR技术检测各组大鼠腹主动脉PI3-KP85a、Akt、eNOS等mRNA表达量变化情况。结果：通过光镜观察主动脉形态,模型组大鼠呈现典型动脉粥样硬化病理改变,血胆固醇、甘油三酯、CRP水平明显增高(P<0.05或P<0.01),HOMA-IRI明显高于其它各组(P<0.01)；参芪复方中药治疗可以促进糖尿病大血管病变GK大鼠体重增长,降低血糖水平,降低血清胆固醇及甘油三酯水平,降低血清胰岛素水平,改善胰岛素抵抗状态,降低血清CRP,减轻炎症反应,抑制主动脉PI3-KP85a、Akt、eNOS等mRNA表达；参芪复方治疗的中药组降低HOMA-IRI水平与阿托伐他汀治疗的西药组有明显差异性(P<0.05)。结论：参芪复方可以恢复并改善其生长发育,改善糖、脂代谢,减轻模型大鼠炎症状态,并可减轻胰岛素抵抗,全面调节达到延缓糖尿病动脉粥样硬化的发生与发展的目的。抑制血管壁PI3-K-Akt-eNOS表达,从而阻止病理性新生血管形成延缓动脉粥样斑块形成和发展,可能是参芪复方保护糖尿病动脉粥样硬化发生发展的分子生物学机制之一。更多还原

【Abstract】 Objective:To observe the influence of PI3-K/Akt signal transduction with ShenQi compound recipe(SQCR) in the diabetes mellitus macroangiopathy GK rat abdominal aorta vessel wall. And to evalute the contribution of SQCR with the function of tonifying Qi and Yin and promoting blood circulation to dissipate stasis to the signal transduction passway. Research the therapeutic mechanism of prevention and cure to the diabetes mellitus macroangiopathy and the reaction mechanism of the organism with Traditional Chinese Medicine (TCM).Methods:Divided 73 GK male rats into four groups randomly: respectively 18 in GK group, drenched normal saline 5ml·kg-1·d-1,19 in model group, drenched normal saline 5ml·kg-1·d-1,18 in atorvastatin groups, drenched atorvastatin calcium suspension 1.6mg·kg-1·d-1,18 in SQCR group, drenched SQCR suspl 1.44g·kg-1·d-1.18 SPF Wistar rat act as the control group, drenched normal saline 5ml·kg-1·d-1. In order to build the diabetes mellitus macroangiopathy model, admin the Nω-nitro-L-arginine methyl ester(L-NAME) 0.1mg·ml-1·d-1 in the drinking water for the model, atorvatatin, SQCR groups with the administration simultaneously. Treated for 35 days, detect the blood glucose, blood fat, blood secum C reactive protein (CRP) and insulin, and the PI3-KP85a、Akt、eNOS mRNA expression in the abdominal aorta vessel wall by real-time PCR.Result:The typical atheromatosis pathoalteration is observed in model group by light microscope in arteriae aorta appearance. Compared with other groups, the blood glucose, fat, CRP and INS raise up in model groups (P<0.05 or P<0.01), and the HOMA-IRI highten too (P<0.01). Increased body weight, degraded the blood glucose, fat, CRP and INS, the GK rats gained improved glycometabolism and fat metabolism, and relieved Inflammatory reaction with insulin resistance. At the same time, the SQCR can also restrain the PI3-KP85a, Akt and eNOS mRNA expression in abdominal aorta vessel wall.Conclusion:SQCR could delay the development of the diabetes mellitus AS by improving the growth and development, gaining weight, depressing blood glucose and blood fat, degrading blood CRP, relieving IRI. One of the possible curing mechanisms in molecular biology is inhibiting the neovascularization for atheromatous plaque by restrain the expressing of PI3-K-Akt-eNOS mRNA in vessel wall.更多还原