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目的:研究阿托伐他汀钙对血脂异常大鼠主动脉组织中bcl-2基因甲基化及bcl-2基因mRNA表达的影响。方法:将Wistar大鼠66只随机分为对照组、血脂异常组和阿托伐他汀钙干预组(简称他汀干预组),每组22只。对照组大鼠给予普通饲料喂养,其他两组给予高脂饲料喂养,以复制血脂异常大鼠模型,从实验第12周开始灌胃,灌胃4周后心脏取血检测血清TC、TG、LDL-C和HDL-C。提取主动脉核蛋白检测基因组DNA总甲基转移酶(DNMT)活力;采用nMSP法检测各组大鼠主动脉组织bcl-2基因启动子区甲基化情况;采用实时荧光定量PCR法检测bcl-2基因mRNA的表达情况。结果:12周高脂饮食可以诱导血脂异常大鼠模型;与血脂异常组比较,他汀干预组血清TC、TG与LDL-C降低,HDL-C升高(均P<0.05);HE染色结果显示,他汀干预组较血脂异常组大鼠动脉粥样硬化病变减轻;与对照组比较,血脂异常组DNMT活力及bcl-2基因启动子区甲基化水平升高,bcl-2基因mRNA表达降低(均P<0.01);与血脂异常组比较,他汀干预组DNMT活力及bcl-2基因启动子区甲基化水平降低,bcl-2基因mRNA表达升高(均P<0.01)。结论:阿托伐他汀钙能够降低bcl-2基因启动子区甲基化水平,增高其mRNA表达,参与延缓动脉粥样硬化的形成及发展。
Objective: To study the effects of atorvastatin calcium on bcl-2 methylation and bcl-2 mRNA expression in the aorta of dyslipidemic rats. Methods: Sixty-six Wistar rats were randomly divided into control group, dyslipidemia group and atorvastatin calcium intervention group (statin intervention group), with 22 rats in each group. The control group rats were fed with normal feed and the other two groups were fed with high fat diet to replicate the model of dyslipidemia rats. The rats in the experimental group were given gavage at the 12th week, -C and HDL-C. Aortic nuclear protein was extracted to detect the activity of total DNA methyltransferase (DNMT) in the genomic DNA. The methylation status of bcl-2 promoter was detected by nMSP method. The bcl- 2 gene mRNA expression. Results: Compared with dyslipidemia group, serum TC, TG, LDL-C and HDL-C were significantly increased (all P <0.05); HE staining showed that 12-week high-fat diet could induce dyslipidemia rats; , The statin intervention group compared with dyslipidemia group atherosclerosis lesion reduced; compared with the control group, dyslipidemia group DNMT activity and bcl-2 gene promoter methylation level increased, bcl-2 gene mRNA expression decreased (All P <0.01). Compared with dyslipidemia group, DNMT activity and bcl-2 promoter methylation level decreased and bcl-2 mRNA expression increased (all P <0.01). Conclusions: Atorvastatin calcium can decrease the methylation level of bcl-2 gene promoter, increase its mRNA expression, and delay the formation and development of atherosclerosis.