摘要
目的探讨动脉粥样硬化斑块发生、发展和破裂机制，以及瑞舒伐他汀对动脉粥样硬化斑块及其稳定性的影响。方法18只普通健康大耳白兔随机分为对照组（6只）、高脂组（6只）和瑞舒伐他汀干预治疗组（6只），建立动脉粥样硬化动物模型。分别采用酶比色法、氧化酶终点法检测血清甘油三脂（TG）、总胆固醇（TC）、高密度脂蛋白一胆固醇（HDL-C）和低密度脂蛋白．胆固醇（LDL—C）水平；双抗体夹心酶联免疫吸附（ELISA）法、HE染色和免疫组织化学染色检测血清白细胞介素-6（IL-6）和热休克蛋白60（hsp60）表达水平；图像分析软件计算血管面积、斑块面积、斑块比例及hsp60阳性表达面积。结果至实验结束时，瑞舒伐他汀干预治疗组动物血清甘油三脂、总胆固醇和低密度脂蛋白．胆固醇水平以及IL-6和hsp60表达水平均低于高脂组（P〈0．05）。相关分析结果显示，手术前后血清IL-6与hsp60表达水平均呈正相关关系（r=0．743，0．894；P=0．008，0．006）。至实验结束时，瑞舒伐他汀干预治疗组动物血管面积、斑块面积、斑块比例及hsp60阳性表达面积均小于高脂组（p〈0．05），斑块性质稳定。结论瑞舒伐他汀可以降低血清甘油三脂、总胆固醇和低密度脂蛋白-胆固醇水平，从而逆转动脉粥样硬化斑块进展。其药理学机制可能与其抑制hsp60参与的炎性反应有关。
Objective To explore the mechanism of the occurrence, development and rupture of atherosclerotic plaque, and the intervention of rosuvastatin on atherosclerosis and the stability of plaque in rabbit model of atherosclerosis. Methods Rabbit models of atherosclerosis were established. Eighteen experimental rabbits were randomly divided into 3 groups： control group （n = 6）, hyper-lipid diet group （n = 6） and rosuvastatin group （n = 6）. Animals in control group received normal diet, while in the other 2 groups received iliac artery endarterium denudation after 4 weeks of hyper-lipid diet feeding, then the 2 groups received hyper-lipid diet and hyper-lipid diet with rosuvastatin （10 mg/d）, respectively. Serum triglyceride （TG）, total cholesterol （TC）, high-density lipoprotein cholesterol （HDL-C） and low-density lipoprotein cholesterol （LDL-C） were determined by enzymic colorimetric and oxidase endpoint method, respectively. The expressions of serum interleukin-6 （IL-6） and heat shock protein 60 （hsp60） were measured by double antibody sandwich enzyme-linked immunosorbent assay （ELISA）, HE staining and immunohistochemical staining. All the examinations were performed at different time points. The rabbits were killed at 10 week. Iliac arteries were isolated and paraffin-embedded slices and immunohistochemical staining of hsp60 were performed. Vascular area, plaque area, plaque proportion and positive hsp60 expressed area were calculated with image analysis software. Results The study showed that serum TG, TC, LDL-C, IL-6 and hsp60 levels in rosuvastatin group were significandy lower than those in hyper-lipid diet group （P〈 0.05, for all） after 6 weeks of operation. Correlation analysis showed that serum IL-6 and hsp60 levels presented positive correlation at both preand postoperation （r=0.743, 0.894; P=0.008, 0.006）. The vascular area, plaque area, plaque proportion and positive hsp60 expressed area of iliac arteries in rosuvas- tatin group were smaller than those in byper-lipid diet group after 6 weeks of operation （P〈 0.05, for all）, and the plaque was stable. Conclusion Rosuvastatin has the effects of lowering the serum TG, TC and LDL-C levels and decreasing the serum IL-6 and hsp60 levels, and thus regress the progression of atherosclerosis. Its pharmacological mechanism may be related to the effect of inhibiting hsp60 in inflammatory reaction.
出处
《中国现代神经疾病杂志》
CAS
2009年第1期40-45,共6页
Chinese Journal of Contemporary Neurology and Neurosurgery
