沉默信息调节因子1基因启动子DNA甲基化在老年钙化性心脏瓣膜病中的临床意义研究  

Clinical significance of SIRT1 gene promoter DNA methylation in elderly patients with calcified valvular heart disease

作　　者：陈泽伦 赵朝阳 王石坚 CHEN Ze-lun;ZHAO Chao-yang;WANG Shi-jian(Department of cardiovascular surgery,Second Affiliated Hospital of Hainan Medical College,Haikou 570311,China)

机构地区：[1]海南医学院第二附属医院心血管外科,海南省海口市570311

出　　处：《中国心血管病研究》2021年第11期979-981,共3页Chinese Journal of Cardiovascular Research

基　　金：2018年海南省卫生计生行业科研项目(76)。

摘　　要：目的探讨沉默信息调节因子1(SIRT1)基因启动子区域DNA甲基化修饰变化与老年钙化性心脏瓣膜病的相关性。方法选取我院2020年2月至2021年1月就诊的老年钙化性心脏瓣膜病患者60例,另纳入同期体检的健康老年40例作为对照。甲基化特异性PCR检测SIRT1基因启动子区域甲基化率,荧光定量PCR检测SIRT1 m RNA表达,ELISA检测SIRT1蛋白和NF-κB蛋白表达。结果观察组SIRT1基因启动子区域甲基化率为63.3%(38/60),显著高于对照组的37.5%(15/40)(P<0.01)。甲基化组SIRT1 m RNA的2-ΔΔCt值显著低于非甲基化组[(0.22±0.05)比(0.36±0.07),P<0.01],甲基化组SIRT1蛋白表达水平显著低于非甲基化组[(82.34±11.56)μmol/L比(143.24±18.73)μmol/L,P<0.01],甲基化组NF-κB蛋白表达水平显著高于非甲基化组[(126.48±17.32)μmol/L比(41.53±7.26)μmol/L,P<0.01]。老年钙化性心脏瓣膜病SIRT1 m RNA与NF-κB蛋白表达呈显著负相关(P<0.05),SIRT1蛋白表达与NF-κB蛋白表达呈显著负相关(P<0.05)。结论老年钙化性心脏瓣膜病患者SIRT1基因启动子区域高甲基化变化,导致SIRT1表达减低,激活炎症反应,可能参与其致病过程。Objective To investigate the relationship between SIRT1 gene promoter DNA methylation and calcified valvular heart disease in the patients. Methods 60 elderly patients with calcified valvular heart disease treated in our hospital from February 2020 to January 2021 were selected, and another 40 healthy old people who received physical examination in the same period were included as control. The methylation rate of SIRT1 gene was detected by MSP analysis. The mRNA expression of SIRT1 was detected by fluorescent quantitative PCR, and the protein expression of SIRT1 and NF-κB were detected by ELISA. Results The methylation rate of SIRT1 gene promoter region in observation group was 63.3%(38/60), which was significantly higher than 37.5%(15/40)that in control group(P<0.01). The 2-ΔΔCt value of SIRT1 mRNA in methylation group was was significantly lower than that in non methylation group [(0.22±0.05) vs.(0.36±0.07),P<0.01]. The expression level of SIRT1 protein in methylation group was significantly lower than that in non methylation group [(82.34±11.56) μmol/L vs.(143.24±18.73) μmol/L,P<0.01]. The expression level of NF-κB protein in methylation group was significantly higher than that in non methylation group [(126.48±17.32) μmol/L vs.(41.53±7.26) μmol/L,P<0.01]. Both the expression of SIRT1 mRNA and SIRT1 protein in calcified valvular heart disease in elderly patients were negatively correlated with NF-κB(P<0.01) protein expression. Conclusion Hypermethylation of SIRT1 gene promoter region in calcified valvular heart disease in the elderly patients may lead to the decrease of SIRT1 expression and activation of inflammatory response, which may be involved in its pathogenesis.

关 键 词：沉默信息调节因子1 老年钙化性心脏瓣膜病 甲基化修饰 

分 类 号：R542.5[医药卫生—心血管疾病]