MicroRNA-146在糖尿病心肌病中的调控作用

目的:探讨微小RNA-146 (miR-146)在糖尿病心肌病(DCM)发病机制中的作用,观察miR-146及其下游靶基因表达水平的变化。方法:60只雄性C57BL/6小鼠随机分为实验(DCM)组和对照(control)组,每组30只,实验组采用低剂量(50 mg/kg链脲佐菌素(STZ)腹腔注射诱导建立糖尿病心肌病模型,对照组给予等量枸橼酸钠缓冲液腹腔注射,建模12周后取心脏做HE和Masson染色观察心脏病理改变,RT-qPCR检测miR-146 a和miR-146b及其下游靶基因白细胞介素-1受体相关激酶1(IRAK1)和TNF受体相关因子6(TRAF6)的mRNA表达,Western blot检测IRAK1和TRAF6的蛋白表达。结果:12周末HE染色显示,DCM组心肌肥大,结构紊乱;Masson染色显示,DCM组心肌内胶原纤维增多;RT-qPCR检测结果显示,DCM组中miR-146a及miR-146b较control组表达明显减少(P 0. 01),IRAK1的mRNA水平明显增高(P 0. 01),而TRAF6的mRNA水平下降(P 0. 01);Western blot检测结果显示DCM组的IRAK1蛋白表达增加,TRAF6的蛋白表达降低(P 0. 01)。结论:miR-146可能通过调节IRAK1介导的炎症反应参与糖尿病心肌损伤的发生发展。

Regulatory effect of miR-146 on diabetic cardiomyopathy

AIM: To investigate the role of microRNA-146 (miR-146) in the pathogenesis of diabetic cardiomyopathy (DCM), and to observe the expression levels of miR-146 and its downstream target genes. METHODS: Male C57BL/6 mice (n=60) were randomly divided into experimental group (DCM, n=30) and control group (control, n=30). The mice in DCM group were intraperitoneally injected with low dose (50 mg/kg) of streptozo-tocin (STZ) to induce diabetic myocardial model, and the mice in control group were given intraperitoneal injection of citrate buffer. At the end of 12 weeks, the hearts were removed, HE and Masson staining were performed to observe the cardiac pathological changes. RT-qPCR were used to detect the expression of miR-146 a and miR-146b and the the mRNA expression of related downstream genes interleukin-1 receptor-associated kinase 1 (IRAK1) and TNF receptor-associated factor 6 (TRAF6). Western blot was used to determined the protein levels of IRAK1 and TRAF6. RESULTS: At the end of 12 weeks, HE staining showed the hypertrophy and structural disorder of the myocardial cells in DCM group. Masson staining showed that the collagen fibers of myocardium were increased in DCM group; RT-qPCR showed that the levels of miR-146a and miR-146b in DCM group were significantly decreased compared with control group (P<0.01). The mRNA levels of IRAK1 was increased (P<0.01), and the mRNA levels of TRAF6 was declined (P<0.01). Western blot showed that compared with control group, the protein expression of IRAK1 was increased in DCM group, and the protein expression of TRAF6 was decreased with statistically significant.CONCLUSION: miR-146 may involve in the occurrence and development of diabetic cardiomyopathy by regulating inflammatory reactions and targeting IRAK1.