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Objective To investigate the effect of remimazolam (RE) on myocardial injury in myocardial ischemia-reperfusion (MI/R) rats and its mechanism. Methods The MI/R rat model was constructed and divided into sham group, MI/R model group, RE low, medium, high dose group (RE-L, RE-M, RE-H group)and Yes associated protein(YAP) inhibitor verteporfin group. Left ventricular ejection fraction (LVEF) and left ventricular fractional shortening(LVFS) were recorded in each group and commercially available kit was applied to detect the level of myocardial injury marker like LDH, c-TnI and CK-MB. The size of myocardial infarction was evaluated by TTC staining. Pathological changes in myocardial tissue was microscopied by HE staining.The apoptosis of myocardial cell was observed by TUNEL method. Expression of Hippo/YAP signaling pathway proteins in myocardial tissue was detected by Western blot. Results Compared to the sham surgery group, the myocardial structure of rats in the model group was disrupted,myocardial cells were reduced, the LVFS and LVEF were decreased, the expression of YAP was greatly reduced. The level of serum LDH, CK-MB, cTnI, myocardial infarction area, myocardial cell apoptosis rate, p-MST1/MST1, p-LATS1/LATS1 and p-YAP expression were all significantly increased(P＜0.05); As compared to model group, the pathological change in myocardial tissue of rats in the low, medium, and high-dose RE groups was greatly reduced. The LVFS and LVEF were increased. The expression of YAP was significantly increased. The serum level of LDH, CK-MB, cTnI, the myocardial infarction area, myocardial cell apoptosis rate, p-MST1/MST1, p-LATS1/LATS1 and p-YAP expression were evidently reduced (P＜0.05). The YAP inhibitor verteporfin reversed the improvement effect of RE on myocardial injury in MI/R rats. Conclusions RE may improve cardiac function in MI/R rats, alleviate myocardial infarction and myocardial cell apoptosis and inhibit myocardial injury by regulating the Hippo/YAP signaling pathway. |
