DNMT3A与CTGF在AAC致大鼠心肌纤维化中的表达及相关性研究

Expression and correlation of DNMT3A and CTGF of abdominal aortic coarctation induced myocardial fibrosis in rats

目的探讨经腹主动脉缩窄(AAC)导致大鼠心肌纤维化中DNA甲基转移酶3A(DNMT3A)与结缔组织生长因子(CTGF)的表达及相关性。方法将60只8周龄雄性SD大鼠随机分为模型组及对照组。模型组行AAC术,对照组行假手术,术后2周处死大鼠获取血液标本,并取心脏。同时测定心重指数,采用ELISA法测量Ⅰ型胶原和CTGF在心肌组织匀浆中的含量,HE和Masson染色法观察心肌组织病理学改变;Western blot法测定DNMT3A和CTGF的表达。结果与对照组比较,模型组大鼠的心重指数显著上升,且心肌组织中Ⅰ型胶原和CTGF的含量明显增加;HE和Masson染色显示,模型组心肌组织呈现明显的胶原沉积;Western blot检测表明模型组DNMT3A、CTGF的含量水平明显高于对照组;DNMT3A和CTGF在大鼠心肌纤维化组织中的表达呈正相关性(r=0.64,P<0.01)。结论 DNMT3A参与心肌纤维化的形成过程,并在其中起到一定的促进作用,可能与CTGF的升高有一定的相关性。

Objective To investigate the expression and correlation of DNA methyltransferase 3A （DNMT3A） and connective tissue growth factor （CTGF） of abdominal aortic coaretation （AAC） induced myocardial fibrosis in rats. Methods 60 male SD rats were randomly divided into model group and control group. The model group underwent abdominal aortic coarctation, while the sham operation was performed in the control group. These rats were execu- ted to collect the blood samples and cardiac tissue, then HW/BW were calculated. The contents of type I collagen and CTGF in myocardial homogenate were measured by ELISA. HE staining and Masson staining were used to ob- serve the degree of myocardial fibrosis. The expressions of DNMT3A and CTGF were detected by Western blot. Re- sults Compared with the control group, the HW/BW of the model group increased significantly. The contents of type I collagen and CTGF in myocardial tissue homogenate of model group were significantly higher than those in the control group. HE staining and Masson staining showed that collagenous fibrosis was found in the myocardium of model group obviously. Western blot showed that the expression of DNMT3A and CTGF in model group was appar- ently higher than that in the control group. There was a positive correlation between the contents of DNMT3A and CTGF in myocardial fibrotic tissue. Conclusion Upregulation of DNMT3A plays an important role in the formation of myocardial fibrosis, which may be related to the elevation of CTGF.