血脂康联合瑞舒伐他汀降脂治疗肾动脉粥样硬化性狭窄的基础研究

The basic research of Xuezhikang combined with rosuvastatin lipid-lowing therapy for atherosclerosis renal artery stenosis

目的通过建立肾动脉粥样硬化性狭窄(ARAS)大鼠模型,观察不同降脂方案的疗效和不良反应,探讨更优的治疗方案。方法⑴90只Wistar大鼠随机分为假手术组(F组)和手术组[普通饲料喂养(N组)与高脂饲料喂养(T组)],手术组采用平行针灸针缩窄法建立大鼠肾动脉狭窄模型,高脂喂养8周后建立ARAS模型。⑵根据不同降脂方案将模型大鼠随机分为5组:生理盐水组(T0组)、血脂康组(T1组)、常规剂量瑞舒伐他汀组(T2组)、常规剂量瑞舒伐他汀联合血脂康组(T3组)、小剂量瑞舒伐他汀联合血脂康组(T4组)。药物干预6周后,检测用药前后各组血脂(TC、TG、HDL-C、LDL-C)、肝功能(ALT、AST)、肾功能(BUN、Scr)及主动脉、肾脏的病理改变。结果⑴与F组相比,N组、T组大鼠血压、肾功能可见明显升高(P <0. 05); T组较N组、F组TC、TG、LDL-C显著升高,HDL-C显著降低(P <0. 05);病理结果显示T组主动脉粥样硬化性改变,肾脏可见肾小管萎缩及不同程度的变性,成功建立ARAS大鼠模型。⑵药物干预6周后,与用药前相比,各用药组均可见TC、TG、LDL-C降低,HDL-C升高(P <0. 05),其中T3、T4两组血脂改善最为明显,T3组略优于T4组,但两组组间差异无统计学意义(P> 0. 05); T2、T3组ALT、AST较用药前显著升高(P <0. 05),而T1、T4组改变不明显(P> 0. 05); T3、T4组BUN、Scr水平均较用药前降低(P <0. 05)。病理结果显示T3、T4组主动脉粥样硬化病变、肾脏肾小管变性程度改善最为明显,但两组差异不大。结论小剂量瑞舒伐他汀联合血脂康治疗ARAS模型大鼠可达到理想降脂效果的同时,对肾脏具有保护作用,且对肝功能的损害作用小。

Objective To observe the therapeutic effects and adverse effect of different lipid-lowering regimens in Atherosclerosis renal artery stenosis （ARAS） rat model and select the optimal treatment. Methods 90 Wister rats were randomly divided into sham operation group （group F） and operation group. The operation group was divided into normal feed group （group N） and high-fat feed group （group T）. We established the rat model in operatino group by narrowing the renal artery with acupuncture needle and 8 weeks of high-fat feeding. According to the different lipid-lowing therapeutic schedules, the T group rats were randondy divided into five groups： the blank group （T0 group）, the Xuezhikang group （T1 group）, the rosuvas- tatin group （T2 group）, the regular dose of rosuvastatin combined with Xuezhikang （T3 group）, the low dose of rosuvastatin combined with Xuezhikang （T4 group）. After 6 weeks of intervention, the serum lipids [ total cholesterol （TC）, triglyceride （TG）, high density lipoprotein-cholesterol （HDL-C）, low density lipoprotein cholesterol （ LDL-C ） ], liver function [ alanine aminotransferase （ ALT ）, aspartate aminotransferase （AST） ], kidney function [blood urea nitrogen （BUN）, serum creatinine （Scr） ] and pathological changes of aorta and kidney were detected before and after treatment. Results （1） The blood pressure, BUN and Scr were significantly increased in N group and T group compared with F group （P 〈 0. 05 ）. TC, TG, LDL-C were significantly increased （ P 〈 0. 05 ） and HDL-C were significantly decreased （ P 〈 0. 05 ） in T group compared with N, T group. According to the pathological section, the aorta in T group had visible atherosclerosis change, the renal tubules were atrophied and decreased. All above, the rat model of ARAS was successfully established. （2） After 6 weeks of drug intervention, compared with prior treatment, TC, TG, LDL-C, BUN and Scr were significant decrease （ P 〈 0. 05 ）, while HDL-C was significantly increased （ P 〈 0. 05 ） in all treatment groups, and the most remarkable change was in T3, T4 group, 3＂3 group was better than T4 group but with no significant difference between T3 and T4 group （ P 〉 0. 05 ）. We found that ALT and AST were significantly increased in T2 and 33 group （P 〈 0.05 ） after treatment. Compared with TO group, pathological lesions of aorta and kidney were reduced best in 33 and T4 group. Conclusions Low dose of rosuvastatin combined with Xuezhikang can achieve ideal lipid-lowing effects. At the same time, it has a protective effect on kidney, and has little damage to liver function.