MRTF-A alleviates myocardial ischemia reperfusion injury via inhibiting TLR4/TRIF signaling pathways

Abstract

Objective To observe the effect of myocardial transcription factor MRTF-A on myocardium inflammation and its mechanism. Methods Totally 30 rats were randomly divided into the sham, ischemia-reperfusion (myocardial ischemia 30 min and reperfusion 2 h), and MRTF-A groups (myocardial ischemia 30 min and reperfusion 2 h & Lentivirus infection MRTF-A) (n=10 each group). Serum myocardial enzyme activity was detected by biochemical analysis, myocardial infarct size detected by TTC, and degree of myocardial injury was measured by HE staining. The TLR4 and TRIF expression was analyzed by immunohistochemistry and qPCR. Results Compared with the sham group, the MRTF-A group significantly increased the activity of serum myocardial enzymes CK-MB and LDH (P<0.05). The infarct area of myocardial tissue was gray-white, and the infarct area was (54.31±3.07)% (P < 0.05). Myocardial fibrosis was disorder, myocardial cell was swollen and burst, and inflammatory cell infiltration was obvious. Protein and mRNA expressions of TRL4 and TRIF were significantly up-regulated (P<0.05). Compared with the ischemia-reperfusion group, the levels of CK-MB and LDH were significantly reduced after myocardial infection with MRTF-A (P<0.05). The myocardial infarction area was significantly reduced to (16.74±4.26)% (P< 0.05). The myocardial structure was nearly normal with mild edema. Protein and mRNA expression of TRL4 and TRIF decreased significantly (P<0.05). Conclusions The overexpression of transcription factor MRTF-A in myocardial cells alleviates the myocardial ischemia reperfusion injury by inhibiting the TLR4/TRIF signaling pathway and reducing the serum myocardial enzyme activity and myocardial damage. Key words: Transcription factor MRTF-A; Myocardial ischemia; Reperfusion injury; Myocardial inflammation; TLR4; TRIF; Signaling pathways; Gene therapy