大黄蛰虫丸对动脉粥样硬化肾缺血模型干预作用的实验研究
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摘要
目的:观察大黄蛰虫丸对改善兔肾动脉粥样硬化性狭窄,减轻肾脏病理改变及其对炎症相关细胞因子的影响。方法:将健康新西兰大耳白兔35只,随机分为模型组、中药中剂量组、中药高剂量组、对照组、空白组。模型组、中药组、对照组普通饲料喂养1周后行左肾动脉银夹缩窄术造模。术后各组予高脂饲料喂养12周,中药组予大黄蛰虫丸灌胃12周,西药组予辛伐他汀灌胃12周,模型组、空白组每天灌服等量蒸馏水,灌胃12周。造模术12周后处死家兔取主动脉、肾动脉和肾脏观察其病理形态学改变,通过图像分析系统(Motic Images Advanced 3.0)测量内膜、中膜厚度和管腔面积,计算肾动脉的狭窄程度。观察各组胆固醇、甘油三酯、低密度脂蛋白、高密度脂蛋白、肾功能变化,用双抗体夹心酶联免疫吸附(ELISA)检测法对TNF-α、IL-1β进行测定。结果:1.成功建立了粥样硬化性肾动脉狭窄缺血兔模型;2.与模型组比较,各治疗组肾动脉狭窄程度和肾动脉壁内、中膜的增厚明显减轻(P<0.01),大黄蛰虫丸各组肾间质纤维化程度轻于模型组(P<0.05);大黄蛰虫丸可明显降低模型兔胆固醇和低密度脂蛋白的水平(P<0.05),降低炎症因子TNF-α、IL-1β的水平(P<0.05);与模型组、辛伐他汀组比较,大黄蛰虫丸高剂量组能明显降低血肌酐值(P<0.05)。结论:大黄蛰虫九可通过抗炎和降血脂而发挥一定的抗动脉硬化的作用,减轻肾脏损害。提示其对粥样硬化血管狭窄引起的肾缺血有一定的预防和治疗作用,为中药防治动脉粥样硬化性’肾动脉狭窄(ARAS)提供了实验依据。
Objective To observe the effects of Dahuang Zhechong Pill on improvement of renal atherosclerosis, pathological changes and inflammatory factor in rabbit. Methods Thirty five healthy New-Zealand white rabbits were randomly divided into groups control, model, high-dose, middle-dose of Dahuang Zhechong Pill (DZP) and blank. Before the silver clip tightening surgery of establish left kidney artery ligation models, the rabbits in model group, TCM group(treated by DZP) and control group(treated by Simvastation) were feed with ordinary food for one week. After the operation, all rabbits were feed with high fatty food for 12 weeks. At the same time, the TCM groups given Dahuang Zhechong Pills in high, medium doses, respectively by intragastric administration.The control group were given Simvastation. The model and the blank groups were given equal amount of distilled water. Aftre 12 weeks, the aorta, renal artery and renal pathological morphology were observed by image analysis system (Motic Images Advanced 3.0). The thickness and area of tunica intima and tunica media were measured. In addition, the sections were analyzed for renal artery stenosis.The levels of serum cholesterol (TC), triacylglycerol (TG), low density lipoprotein(LDL),high density lipoprotein (HDL), renal function were measured. ELISA was used to measure the contents of TNF-a、IL-1β. Results 1. Atherosclerotic renal artery stenosis-caused renal ischaemia models were established successfully in rabbit. 2. Compared with the model group, the renal artery stenosis and thickness of renal artery tunica media in treated groups were decreased significantly (P<0.01). At the same time, the degrees of renal interstitial fibrosis were decreased (P<0.05) in TCM groups compared with the model group. The levels of serum cholesterol (TC) and low density lipoprotein(LDL) were declined in TCM group(P<0.05). The contents of TNF-a、IL-1βwere decreased (P<0.05). Compared with the model group and the control group, the blood creatinine in the high-dose group of DZP was decreased significantly (P<0.05). Conclusion Dahuang Zhechong pill suppresses the development of atherosclerosis and reduce kidney damage by modulating blood lipid and anti-inflammation.It is suggested that DZP is beneficial for prevention and treatment on AS-caused renal ischemia and provide some experimental basis for the prevention of atherosclerotic renal artery stenosis (ARAS).
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