过氧化物酶体增殖物活化受体-α启动子区甲基化:诱导肝内脂滴形成及加快非酒精性脂肪性肝病进程  

The methylation of Peroxisome proliferator-activated receptor-α promoter: induce intrahepatic fat deposition and promote the progress of nonalcoholic fatty liver disease

作　　者：屈飞[1] 何杰[1] 聂玉强[1] 李瑜元[1] 周永健[1] 

机构地区：[1]广州医科大学附属市第一人民医院消化内科广州消化疾病中心,广东广州510180

出　　处：《胃肠病学和肝病学杂志》2016年第11期1279-1282,共4页Chinese Journal of Gastroenterology and Hepatology

基　　金：广州市科信局科技惠民项目(2014Y2-00139)

摘　　要：目的探讨过氧化物酶体增殖物活化受体-α(PPAR-α)甲基化与非酒精性脂肪性肝病(NAFLD)的相关性。方法收集15例NAFLD患者肝脏组织及11例正常对照组肝脏组织,HE染色明确病理分型,RT-PCR、Western blotting分别检测PPAR-αmRNA及蛋白的表达水平,选取其中的10对行焦磷酸测序检测PPAR-α启动子区甲基化水平。结果与对照组比较,NAFLD组肝脏组织可见明显脂肪沉积,PPAR-αmRNA及蛋白表达均降低(P<0.05),PPAR-α启动子区甲基化水平升高(P=0.025),启动子区甲基化发生率与PPAR-α蛋白表达量呈负相关(r=-0.878,P=0.009)。结论正常人肝脏发生脂肪变时,不仅有肝细胞内脂肪沉积,且伴有PPAR-α表达降低,降低原因之一是该基因启动子区发生甲基化,从而加快NAFLD的进程。Objective To study the relationship between the methylation of Peroxisome proliferator-activated receptor-alpha （PPAR-α） promoter and non-alcoholic fatty liver disease（NAFLD）. Methods Fifteen patients with NAFLD and 11 healthy individuals as controls were enrolled. Hematoxylin-eosin staining was applied to definite pathological classification. RT-PCR and Western blotting were used to assess the mRNA and protein expressions of PPAR-α. Bisul-fire cloning sequencing method （BSP） was used to assess the degree of methylation in 10 pairs of them. Results There were visible fat deposits in liver tissue of NAFLD group. Compared with normal group, the expressions of PPAR-α mRNA and protein were decreased in NAFLD group （P 〈 O. 05） ; while the degree of methylation in PPAR-ct promoter was increased （P =0. 025）. The protein expression was significantly （negatively） correlated with the degree of methylation in PPAR-α promoter （r = - 0.878, P = 0. 009）. Conclusion When normal livers turn to NAFLD, not only have in-trahepatic fat deposition in the cells, but also accompanied by expression of PPAR-α decreased. The methylation of PPAR-α promoter may be one reason for the decreasing, which can promote the progress of NAFLD.

关 键 词：非酒精性脂肪性肝病 PPAR-Α DNA甲基化 

分 类 号：R575.5[医药卫生—消化系统]