阿托伐他汀对鼠动脉粥样硬化基质金属蛋白酶和蛋白激酶C的影响

The Effect of Atovastatin on Protein Kinase C and Matrix Metalloproteinases in Rat Model of Atherosclerosis

目的观察鼠动脉粥样硬化时基质金属蛋白酶及蛋白激酶C的表达及阿托伐他汀的干预作用,从而初步探讨他汀类抑制基质金属蛋白酶的机制。方法将50只清洁级雌性SD大鼠分为对照组(n=10,正常饮食)、模型组(n=20,维生素D3+高脂饲料+正常饮食)和阿托伐他汀组(n=20,维生素D3+高脂饲料+阿托伐他汀),4个月后处死试验鼠并取主动脉起始部进行光镜和电镜观察,其余部分用于免疫印迹法检测基质金属蛋白酶和蛋白激酶C的表达。各组动物分别于实验前及实验结束时空腹股动脉取血,分离血清,检测血清总胆固醇、甘油三酯、低密度脂蛋白和高密度脂蛋白水平。结果模型组鼠血浆总胆固醇、甘油三酯和低密度脂蛋白水平显著高于对照组(P<0.01),阿托伐他汀能显著降低血脂学水平(P<0.01);模型组鼠主动脉基质金属蛋白酶2和9及蛋白激酶C的表达显著高于对照组(P<0.01),阿托伐他汀能显著抑制基质金属蛋白酶2和9及蛋白激酶C的表达(P<0.01);阿托伐他汀组鼠主动脉病理学改变显著。结论阿托伐他汀抑制蛋白激酶C,在抑制基质金属蛋白酶的表达、稳定粥样斑块过程中可能起重要作用。

Aim To investigate the expression of matrix metalloproteinases （MMP） and protein kinase C （PKC） in aorta of atherosclerofie rats and effect of atorvastatin on them. Methods Fifty female Sprague-Dawley rats were randomly divided into normal diet group （ n = 10, control group） ; vitamin D3 injection and high cholesterol diet group （ n = 40）. After 8 weeks, vitamin D3 injection and high cholesterol diet rats were randomly switched to receive atorvastatin [ 5 mg/（kg·d） ] （ n = 20, atorvastatingroup） or normal diet （n=20, modal group）. Another eight weeks later , allthe ratswere killed and some of their aortas were observed by light and electron microscope, the left aortas were removed for western hlot analysis to detect MMP-2, MMP-9 and PKC; at the begin and end of experiment, serum was collected for serum lipid determining. Results There were no significant changes in serum lipids at the beginning of experiment between the groups, but after two months, cholesterol, low density lipoprotein （LDL）, triglyceride （TG） of atorvastatin group were significantly lower than those of model group （ all P 〈0.01 ）, hut higher than control group （ all P 〈0.01）. The pathologic changes of atorvastatin group were less serious than those of model group, there showed no any pathological changes in control group. MMP-2, MMP-9 and PKC were significantly higher in the mndel group than those in the control group （ all P 〈 0.01 ）, But compared with the model group, MMP-2,MMP-9 and PKC levels were markedly lower in the atorvastain group （ all P 〈 0.01 ）. Conclusions Atorvastafin inhibiting PKC expression may play an important role in depressing the express of MMP, stabilizing the atherosclerotic plaque.