microRNA-410通过靶蛋白HMGB1参与调控心肌缺血再灌注损伤的实验研究

We found that HMGB1 was involved in the mycardial and pulmonary ischemic reperfusion injury with cardiopulmonary bypass. The mechanism is still unclear. TargetScan,starBase and Pic tar predict microRNA-410 is well correlated with HMGB1. Furthermore, we showed that expression of microRNA-410 was increased 90 min after reperfusion with Northern-blot analyse. Therefore we suppose that microRNA-410 regulates myocardial ischemic reperfusion injury by targeting HMGB1 pathway. This project intends to further build the recombinant adenoviral vector carrying justice microRNAs-410 and antisense microRNAs-410 transfected cardiomyocytes to prove our hypothesis by using stem-loop real-time PCR and dual luciferase reporter system technology. It will clarify the microRNAs-410 involved in the mechanism of myocardial ischemic reperfusion injury and will provide scientific basis for the establishment of microRNA-410 as a new target for treatment of myocardial ischemic disease.

我们已经证明了HMGB1参与体外循环心肺缺血再灌注早期损伤（IRI）。但是其具体的调控机制尚未清楚。TargetScan等预测microRNA-410与HMGB1相关性优良。进一步Northern-blot分析显示：心肌microRNA-410再灌注后90min表达明显提高。因此，我们提出心肌IRI新机制：microRNA-410通过靶蛋白HMGB1参与调控心肌IRI。本项目拟构建重组腺病毒载体携带正义microRNA-410和反义寡microRNA-410转染心肌细胞及大鼠心脏，采用stem-loop RT-PCR、报告基因双荧光酶等正向、反向抑制技术，旨在获得心肌缺血再灌注损伤时microRNA-410参与调节HMGB1/NF-κB信号通路的可靠证据。本项目将阐明microRNA-410参与心肌IRI新机制，为确立microRNA-410作为心肌缺血性疾病治疗新靶点提供充分的科学依据。

我们已经证明了HMGB1参与体外循环心肺缺血再灌注早期损伤。但是其具体的调控机制尚未清楚。Northern-blot分析体外循环缺血再灌注心肌显示：microRNA-410在再灌注后90min表达明显提高。因此，我们提出心肌缺血再灌注损伤的新机制，即：microRNA-410通过靶蛋白HMGB1参与调控心肌缺血再灌注损伤。本项目在动物模型和细胞实验中，发现microRNA-410在进一步的研究中表达微弱，和HMGB1表达相关性不成立。