【作者】 庄灿；

【导师】 谢春光；

【作者基本信息】 成都中医药大学 ， 中医内科学， 2010， 博士

【摘要】 目的：通过对糖尿病GK大鼠使用具有益气养阴、活血化瘀的参芪复方,从.基因水平、分子水平及整体水平来评价参芪复方对实验大鼠的治疗效果。从血管紧张素及其受体的角度来说明参芪复方防治糖尿病大血管病变的机制。方法：73只糖尿病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,同时予Wistar大鼠18只作为正常对照组。其中模型、西药及中药三组予以内皮型一氧化氮合成酶(eNOS)抑制剂Nω-硝基-L-精氨酸甲酯(L-NAME 0.1mg·ml-1·d-1)加入饮用水中进行造模,造模时间为35天。Wistar对照组用普通饲料饲养,其余各组均用高脂饲料饲养。造模的同时开始给药,Wistar对照组按照5ml·kg1·d-1灌服生理盐水,GK组按照5ml·kg-1·d-1灌服生理盐水,模型组按照5ml·kg-1·d-1灌服生理盐水,西药组按照1.6mg·kg-1·d-1灌服阿托伐他汀钙悬液,中药组按照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C反应蛋白(CRP)及血清血管紧张素Ⅱ(AngⅡ);利用免疫组化技术测定大鼠腹主动脉血管紧张素Ⅱ1型受体(AT1R)和血管紧张素Ⅱ2型受体(AT2R)的积分光密度值；用实时荧光定量聚合酶链反应(RT-PCR)技术检测大鼠腹主动脉血管紧张素Ⅱ1型受体信使核糖核酸(AT1RmRNA)的表达量；用免疫印迹法测定细胞间黏附分子-1(ICAM-1)和血管细胞黏附分子-1(VCAM-1)在胸主动脉的表达。结果：通过光镜观察主动脉病理形态,模型组呈现典型动脉粥样硬化病理改变,其血糖、总胆固醇(TC)、甘油三酯(TG)、CRP及AngⅡ水平明显高于其他四组(P<0.05或P<0.01)。参芪复方治疗可以促进糖尿病大血管病GK大鼠的体重增长,降低血糖水平,降低血清TC、TG、CRP及AngⅡ水平；可以降低大鼠主动脉血管壁中AT1RmRNA的表达,减少AT1R蛋白的合成,增加AT2R蛋白的合成；参芪复方还可以减少主动脉中ICAM-1和VCAM-1蛋白的含量。结论：参芪复方可以改善糖尿病大血管病变GK大鼠生长发育,改善其糖、脂代谢,减轻炎症反应,延缓糖尿病动脉粥样硬化的进展。而降低血清AngⅡ水平,抑制主动脉血管壁AT1RmRNA表达及AT1R蛋白合成,增加AT2R蛋白的合成可能是参芪复方治疗糖尿病大血管病变的机制之一。更多还原

【Abstract】 Objective:To elvaluate the therapeutic effect of ShenQi compound recipe(SQCR) on the diabetes mellitus macrovasculopathy GK rat,which has the function of tonifying Qi and Yin and promoting blood circulation to dissipate stasis,in the level of gene, molecular and cell leve.To demonstrate the mechanism of SQCR for diabetes mellitus macrovasculopathy from the view of angiotensin and its recepors.Methods:73 GK male rats were divided 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 rats in the control group was drenched normal saline 5ml·kg-1·d-1. In order to build the diabetes mellitus macroangiopathy model, the model, atorvatatin, SQCR groups were administered with the Nω-nitro-L-arginine methyl ester(L-NAME) 0.1mg·ml-1·d-1 in the drinking water for 35 days. After sacrifice, detect the blood glucose, blood fat, blood secum C reactive protein (CRP) and AngiotensinⅡ;dectect the angiotensinⅡtype 1 receptor(AT1R)mRNA expression in the abdominal aorta vessel wall by real-time PCR; dectect the integral optical density of AT1R and AT2R in the abdominal aorta vessel wall by immunohistochemistry;detect the intercellular adhesion molecule-1(ICAM-1) and vascular cell adhesion molecule-1(VCAM-1) by western blot.Result:The typical atheromatosis pathoalteration was observed in model group by light microscope in arteriae aorta appearance. Compared with other groups, the blood glucose, fat, CRP and AngⅡraised up in model groups (P<0.05 or P<0.01). Increased body weight, degraded blood glucose, fat, CRP and AngⅡand relieved inflammatory reaction was observed in the GK rats treated by SQCR. in addition, the SQCR can also downregulate the AT1RmRNA expression, decrease the synthesis of AT1R, enhance the AT2R, decrease the ICAM-1 and VCAM-1 in abdominal aorta vessel wall.Conclusion:SQCR could delay the development of diabetes mellitus AS by improving the growth, gaining weight, depressing blood glucose and blood fat, degrading blood CRP and AngⅡ.One of the possible treatment mechanisms in molecular biology is to decrease the AngⅡin the surem,downregulate the expression of AT1RmRNA and synthesis of AT1R,and increase the synthesis of AT2R in vessel wall.更多还原