Hyperlipidemia Affecting Genomic DNA、Bcl-2Methylation In Wistar Rats

Objective To study the alone effect of Hyperlipidemia on genomic DNA methylationand DNA methyltransferase activity in aortic tissue of Wistar rats.To investigate themethylation status of bcl-2gene promoter and mRNA expression of bcl-2in aortic tissue ofhyperlipidemia Wistar rats. Methods44healthy clean level male Wistar rats wererandomized into two groups: negative control group and Hyperlipidemia group. The rats innegative control group were fed a normal chaw, and the another group were fed a chawformula as designed.The rats were fed for three months. Heart blood was then drawn fordetection of serum total cholesterol、triglyceride、low density lipoprotein-cholesterol、highdensity lipoprotein-cholesterol; aortic genomic DNA was extracted for detection of genomicDNA methylation levels; and aortic nucleoprotein was extracted for detection of DNAmethyltransferase activity; The Nested methylation specific poly merase chain reaction(nMSP) method was used to detect bcl-2gene methylation in aortic tissue of control groupand hyperlipidemia group in Wistar rats. The expression of bcl-2mRNA in aortic tissue ofcontrol group and hyperlipidemia group in Wistar rats was detected by real-time quantitativepolymerase chain reaction. Results1、The rats in negative control group were fed anormal chaw, and the another group were fed a chaw formula as designed.The rats were fedfor three months. Serum total cholesterol、 triglyceride (TG)、 low density lipoproteincholesterol (LDL-C) levels of the hyperlipidemia group was significantly higher than that ofthe control groups (P<0.05), but there was no statistically significant difference in highdensity lipoprotein cholesterol (HDL-C) levels between the hyperlipidemia group and the control group (P>0.05).2、Compared with the control group, high hyperlipidemia increasedDNA methyltransferase activity and promoted DNA demethylation in in Wistar rats (P<0.05).Compared with the control group， hyperlipidemia group significantly increased DNAmethyltransferase activity and methylation status of bcl-2gene promoter (P<0.01)，theexpression of bcl-2mRNA was decreased in hyperlipidemia groups (P<0.01).Conclusion1、The rats were fed a chaw formula as designed. Serum total cholesterol、triglyceride (TG)、low density lipoprotein cholesterol (LDL-C) levels of the hyperlipidemiagroup was significantly higher than that of the control groups, show Hyperlipidemia modelrats modeling were successful.2、Hypomethylation induced by hyperlipidemia is one of theimportant mechanisms for the development of atherosclerosis.3、 Increased DNAmethyltransferase activity suggest that the former may be a compensatory reaction against thelatter.4、The methylation of bcl-2may be involved in the evolution of atherosclerosis.Thehypermethylation status of bcl-2gene promoter and down-regulating the expression of bcl-2mRNA induced by hyperlipidemia is one of the important mechanisms for the development ofatherosclerosis and may be an early event in the carcino-genesis of atherosclerosis.The bcl-2gene promoter region methylation study provide new ideas for prevention and therapy ofatherosclerosis.5、The high methylation status of bcl-2gene promoter region of inhibition ofgene expression in rat aortic tissue, leading to apoptosis and proliferation imbalance, therebycontributing to the development of AS.