阿托伐他汀对大鼠动脉粥样硬化血红素氧合酶-1表达的影响

Effect of atorvastatin on the expression of heme oxygenase-1 in atherosclerotic rats

目的:建立大鼠动脉粥样硬化模型,探讨阿托伐他汀对大鼠动脉粥样硬化血红素氧合酶-1(HO-1)表达的影响。方法:36只健康雄性Wistar大鼠随机分为正常对照组(n=10,普通饮食)、模型对照组〔n=13,维生素D3(VD3)+高脂饮食〕和阿托伐他汀治疗组(n=13,VD3+高脂饮食和阿托伐他汀)。14周后处死大鼠,取血测定血清总胆固醇(TC)、甘油三脂(TG)、低密度脂蛋白胆固醇(LDL-C)及高密度脂蛋白胆固醇(HDL-C)水平;HE染色观察主动脉壁病理组织学变化;免疫组织化学法、逆转录-聚合酶链反应法(RT-PCR)检测斑块内HO-1及mRNA的表达。结果:模型对照组和阿托伐他汀治疗组血清脂质水平差异无统计学意义(P>0.05),均显著高于正常对照组(P<0.05);阿托伐他汀治疗组和模型对照组斑块内HO-1阳性细胞面积/扫描面积明显高于正常对照组[(6.16±2.05)(P<0.05)],阿托伐他汀治疗组(24.26±3.04)显著高于模型对照组[(16.20±2.33)(P<0.05)];模型对照组HO-1 mRNA的表达(0.998±0.019)较正常对照组(0.478±0.018)明显升高(P<0.05),阿托伐他汀治疗组(2.572±0.015)较模型对照组进一步升高(P<0.05)。结论:阿托伐他汀可能通过上调HO-1的表达而发挥其抗动脉粥样硬化的保护作用,其具体作用机制有待进一步研究。

Objective：To establish animal model of rats with atheroscle rosis and investigate the influence of Atorvastatin on the expression of heine oxygenase-1 （HO-1） in atherosclerotic rats. Method：Thirty-six healthy male wistar rats were randomly divided into normal control group （ n = 10, normal diet）, model control group （ n = 13, vitamin D3 （VD3） ＋ high-cholesterol diet） and Atorvastatin group （n = 13, VD3 ＋ high-cholesterol diet and Atorvastatin） .The rats were killed at 14 Weeks, fasting blood samples were collected and total cholesterol（ TC）, triglyceride（TG） ,low-density lipoprotein cholesterol （LDL-C） and high-density lipoprotein cholesterol（HDL-C） levels were determined. The aortic tissue was obtain ed for observing pathohistologic changes with hematoxylin and eosin （HE） staining; The expressions of HO-1 and mRNA in atherosclerotic plaques in each group were detected and measured by means of immunohistochemistry and reverse transcription polymerase chain reaction（RT-PCR）. Result： The serum cholesterol level were similar in the model control group and Atorvastatin group （P 〉 0.05）, which were higher than normal control group （P 〈 0.05 ） ; The positive ratio of HO-1 in Atorvastatin group and model control group was higher than that in normal control group[ （6.16± 2.05）（P 〈 0.05）], and that in Atorvastatin group （24.26 ±3.04）was higher than model control group[ （16.20± 2.33） （ P 〈 0.05）] ; The expression of HO-1mRNA in model control group （0.998± 0.019）was higher than that in normal control group [（0.478± 0.018）（ P 〈 0.05）], compared with model control group, the expression of HO-1 mRNA in Atorvastatin group （2. 572 ± 0.015）increased significantly （P 〈 0.05）. Conclusion： Atorvastatin may prevent atherosclerosis by increasing the expression of HO-1, and its detailed mechanism need to be further investigated.