Objective To investigate the promoter methylation and mRNA expression of Bel - 2 in aortic tissue from Wistar rats with hyperlipidemia. Methods Forty - four Wistar rats were equally randomized into control group ( Group C) and hyperlipidemia group ( Group H) , in which normal and high - fat formula diets were given, respectively, for 16 weeks. Serum total cholesterol (TC) , triglyceride (TG) , low density lipoprotein - cholesterol ( LDL - C) , high density lipoprotein - cholesterol (HDL - C) were measured, whereas aortic nucleoprotein was extracted for detection of DNA methyltransferase ( DNMT) activity. The methylation specific polymerase chain reaction ( MSP) method and real -time quantitative polymerase chain reaction were applied for assessment of Bel - 2 gene methylation and mRNA expression in aortic tissue. Results Significant elevation of TC, TG and LDL - C were induced in Group H ( P < 0. 01) . Moreover, there were significant raises of DNMT activity and methylation of Bel -2 promoter in Group H, so was the down -regulation of Bel - 2 mRNA ( P < 0. 05 ) . Conclusion The methylation of Bel - 2 promoter in hyperlipidemia model, which induces the down - regulation of Bel - 2, may be involved in the evolution of atherosclerosis.%目的 研究Bcl-2基因启动子区甲基化及mRNA表达在高脂血症(hyperlipidemia) Wistar大鼠主动脉组织中的作用.方法 将44只Wistar大鼠随机分为对照组和高脂组,每组22 只.对照组给予普通大鼠饲料,高脂组给予高脂饲料.持续喂养16周后心脏取血检测血清总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)指标.提取主动脉核蛋白检测基因组DNA总甲基转移酶活力;采用巢式MSP (nMSP)法检测两组大鼠主动脉组织Bcl-2基因启动子区甲基化情况;采用实时荧光定量PCR检测Bcl-2基因在两组大鼠主动脉组织中mRNA的表达情况.结果 16周高脂饮食可以建立高脂血症大鼠模型,TC、TG、LDL-C升高(P<0.01),HDL-C降低(P＞0.05); HE 染色法结果显示高脂组大鼠动脉粥样硬化(AS)病变.高脂血症作用下基因组DNA总甲基转移酶活力及Bcl-2基因启动子区甲基化水平增高,与对照组比较,差异有统计学意义(P＜0.01),且Bcl-2基因mRNA表达降低,与对照组比较,差异有统计学意义(P＜0.01).结论 高脂血症作用下Bcl-2基因启动子区甲基化水平增高,mRNA表达降低,参与了AS的发生发展,可能是AS发生发展的重要机制之一,是AS发生的早期事件.
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