阿托伐他汀对鼠动脉粥样硬化蛋白激酶C和C反应蛋白的影响

The effects of atorvastatin on protein kinase C and C-reactive protein in experimental atherosclerosis

目的为了阐明阿托伐他汀对动脉粥样硬化独立于其降脂效应的保护作用，研究了其对大鼠动脉粥样硬化模型中蛋白激酶C（PKC）和C反应蛋白（cRP）表达的影响。方法将雌性SD大鼠50只随机分为正常饮食（n=10，对照组），维生素B注射＋高脂饮食组（n=40）。8个星期后，维生素D3注射＋高脂饮食组大鼠再随机的予以阿托伐他汀治疗（n=20，阿托伐他汀组，每天按5mg·kg^-1喂食阿托伐他汀）或予以正常饮食（n=20，模型组）。8个星期后处死试验鼠并取主动脉做病理切片，进行光镜和电镜观察，其余的主动脉用于免疫印迹法检测蛋白激酶C。各组动物分别于实验前及实验结束时取血检测血脂及C反应蛋白水平。结果阿托伐他汀能显著降低鼠血浆总胆固醇、甘油三酯、低密度脂蛋白水平；阿托伐他汀组鼠的主动脉病理学改变比模型组显著改善；对照组未见明显的病理学改变；模型组中CRP水平[（18．64±0．94）mg／L]显著高于对照组水平[（9．21±0．21）mg／L]（P〈0．05），CRP水平在对照组和阿托伐他汀组[（12．52±0．65）mg／L]之间也存在显著性差异（P〈0．05）。PKC在模型组（7786．12±264．75）和阿托伐他汀组（4267．57±233．94）中的表达均显著性高于对照组（2468．75±145．53）（P〈0．05），但和模型组相比较，阿托伐他汀组中PKC水平显著降低（P〈0．01）。结论阿托伐他汀的益处不仅仅在于降低血脂，其抑制PKC和炎症反应在抗动脉粥样硬化的血管保护中可能起重要的作用。

Objective To reveal the protective effects of atorvastatin against atherosclerosis independent of cholesterol-lowering effect, we investigated the effects of atorvastation on the expression of protein kinase C （PKC） and C-reactive protein in experimental atherosclerosis of rats. Method 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 randomized to receive either atorvastatin （5 mg.kg^-1. d^-1 ） （ n = 20, atorvastatin group） or normal diet （ n = 20, model group）. Another eight weeks later, all rats were killed and part of their aortas were examined by light and electron microscope and the left were removed for western blot analysis to measure PKC; At the begin and end of experiment, serumcollected for lipid and C-reactive protein determining deterruination. Results Cholesterol, low-density lipoprotein, triglyceride levels in atorvastatin group were significantly lower than those in model group but higher than control group. The pathologic changes in atorvastatin group were less severe than those in model group, there showed no any pathological changes in control group. The levels of C-reactive protein in model group[（ 18.64 ±0. 94） mg/L] were higher than those in control group [（9.21 ± 0.21 ） mg/L] （P 〈 0.05）. C-reactive protein levels also differed significantly between control and atorvastatin group （12.52± 0.65 mg/L）（ P 〈 0.05）. PKC levels were significantly higher in model group （7786.12 ± 264.75） and atorvastatin group （4267.57 ± 233.94） than in control group （2468.75 ± 145.53） （all P 〈 0.05）. But compared with model group, PKC levels were markedly lower in the atorvastatin group （ P 〈 0.01 ）. Conclusions Atorvastatin may be useful not only as a cholesterol-lowering agents but also as anti-arteriosclerotic agent that provide vascular protection by inhibition PKC expression and inflammatory reaction