研究miR-219下调TGFBR2影响ENDMT途径抑制急性心肌梗死

目的: 主要是miR-219通过对TGFBR2调控机制,介导ENDMT途径缓解急性心肌梗死的发展。方法: qRT-PCR检测AMI患者及AMI小鼠血清中miR-219的表达量;过microRNA靶基因数据库TargetScan进行筛选预测;萤光素酶报告基因法及qRT-PCR分析TGFBR2与miR-219的调控机制;通过心脏超声心动图检测AMI小鼠心肌注射miR-219慢病毒4周后的血分数(LVEF);采用qRT-PCR检测心肌注射miR-219慢病毒的AMI小鼠中Nppa 的mRNA的表达量;通过Masson’s trichrome染色法检测小鼠4周后左心室纤维化变化;使用α平滑肌肌动蛋白(α-SMA)对小鼠左室切片进行免疫组化分析;通过Western blot检测P-smad2、P-smad3及TGFBR2缺氧诱导蛋白磷酸化的表达水平。结果: miR-219对AMI有调控作用;miR-219可抑制TGFBR2的mRNA表达,而miR-219 inhibitor可以抑制这种下调效果,miR-219对TGFBR2具有抑制调控性;miR-219可抑制急性心肌梗死的进程,促进梗死心肌功能的恢复;miR-219能促进AMI小鼠心肌组织血管的新生和成熟,最终心脏收缩能力上升,心功能恢复;miR-219能抑制TGFBR2抑制EndMT途径,导致缓解AMI的病理进程。结论: miR-219能通过抑制TGFBR2影响EndMT途径,心肌纤维化减少,促进血管的新生和成熟,心功能恢复,抑制AMI的病理发展。

Inhibition of Acute Myocardial Infarction by miR-219 on ENDMT Pathway by Targeting TGFBR2

Objective: miR-219 mediated the development of acute myocardial infarction through the regulation mechanism of TGFBR2 and the ENDMT pathway. Methods: The expression of miR-219 in the serum of AMI patients and mice was detected by qRT-PCR. The target gene of miR-219 was screened in gene database of microRNA. The regulatory mechanism of TGFBR2 and miR-219 was examined by luciferase reporter gene and qRT-PCR.The blood scores (LVEF) of AMI mice were measured 4 weeks after myocardial injection of miR-219 lentivirus (LVEF) by cardiac echocardiography. The mRNA expression of Nppa in AMI mice injected with miR-219 lentivirus was detected by qRT-PCR. The changes of left ventricular fibrosis in mice were detected by Masson’s trichrome staining. immunohistochemical analysis of the left ventricular section of mice was performed using spla-sma. Expression levels of P-smad2, P-smad3 and TGFBR2 hypoxia induced protein phosphorylation were detected by Western blot. Results: miR-219 can regulate AMI. miR-219 inhibited the mRNA expression of TGFBR2, while miR-219 inhibitor inhibited the down-regulation effect. miR-219 can inhibit the process of acute myocardial infarction and promote the recovery of myocardial function of infarction. miR-219 can promote the angiogenesis and maturity of the myocardial tissue of AMI mice, and eventually the cardiac contractility increases and the cardiac function recovers. miR-219 can inhibit the inhibition of EndMT pathway by TGFBR2, leading to the alleviation of the pathological process of AMI. Conclusion: miR-219 can inhibit the EndMT pathway by inhibiting TGFBR2, reduce myocardial fibrosis, promote angiogenesis and maturity, recover cardiac function and inhibit the pathological development of AMI.