瑞马唑仑减轻心肌缺血/再灌注大鼠心肌损伤

doi:10.16352/j.issn.1001-6325.2024.09.1243

基础医学与临床 ›› 2024, Vol. 44 ›› Issue (9): 1243-1248.doi: 10.16352/j.issn.1001-6325.2024.09.1243

瑞马唑仑减轻心肌缺血/再灌注大鼠心肌损伤

甄磊^1*, 张懿兰¹, 王晓娜¹, 张小琼²

保定市第二医院1.麻醉科;2.心内二科, 河北保定 071000

收稿日期:2024-01-10 修回日期:2024-05-09 出版日期:2024-09-05 发布日期:2024-08-30
通讯作者: ^*lann66444002@163.com
基金资助:
保定市科技计划项目(2041ZF206)

Remimazolam alleviates myocardial injury of rats with myocardial ischemia-reperfusion

ZHEN Lei^1*, ZHANG Yilan¹, WANG Xiaona¹, ZHANG Xiaoqiong²

1. Department of Anesthesiology; 2. Second Department of Cardiology, the Second Hospital of Baoding, Baoding 071000, China

Received:2024-01-10 Revised:2024-05-09 Online:2024-09-05 Published:2024-08-30
Contact: ^*lann66444002@163.com

摘要/Abstract

摘要： 目的探究瑞马唑仑(RE)对心肌缺血/再灌注(MI/R)大鼠心肌损伤的影响,并探讨其可能机制。方法将大鼠分为假手术组、MI/R模型组、RE低、中、高剂量组(RE-L、M、H组)、Yes相关蛋白(YAP)抑制剂维替泊芬(verteporfin)组。检测各组大鼠左心室射血分数(LVEF)、左心室短轴缩短率(LVFS);试剂盒测定乳酸脱氢酶(LDH)、肌钙蛋白(c-TnI)、肌酸激酶同工酶(CK-MB)水平;TTC染色评估心肌梗死面积,HE染色观察心肌组织病理改变;TUNEL法测定心肌细胞凋亡;Western blot分析心肌组织Hippo/YAP信号通路蛋白表达。结果相较于假手术组,模型组大鼠心肌结构破坏,心肌细胞减少,LVFS、LVEF降低,YAP表达显著降低,血清LDH、CK-MB、cTnI水平、心肌梗死面积、心肌细胞凋亡率、p-MST1/MST1、p-LATS1/LATS1、p-YAP表达显著升高(P＜0.05);与模型组相比,RE低、中、高剂量组大鼠心肌组织病理改变均明显减轻,LVFS、LVEF升高,YAP表达显著升高,血清LDH、CK-MB、cTnI水平、心肌梗死面积、心肌细胞凋亡率、p-MST1/MST1、p-LATS1/LATS1、p-YAP表达显著降低(P＜0.05);YAP抑制剂verteporfin组逆转RE对MI/R大鼠心肌损伤的改善。结论 RE可能通过调节Hippo/YAP信号通路改善MI/R大鼠心功能,减少心肌梗死和心肌细胞凋亡,改善心肌损伤。

关键词: 心肌缺血/再灌注, 心肌损伤, 瑞马唑仑, Hippo/Yes相关蛋白

Abstract: 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.

Key words: myocardial ischemia-reperfusion, myocardial injury, remimazolam, Hippo/Yes associated protein

中图分类号:

R614

甄磊, 张懿兰, 王晓娜, 张小琼. 瑞马唑仑减轻心肌缺血/再灌注大鼠心肌损伤[J]. 基础医学与临床, 2024, 44(9): 1243-1248.

ZHEN Lei, ZHANG Yilan, WANG Xiaona, ZHANG Xiaoqiong. Remimazolam alleviates myocardial injury of rats with myocardial ischemia-reperfusion[J]. Basic & Clinical Medicine, 2024, 44(9): 1243-1248.

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瑞马唑仑减轻心肌缺血/再灌注大鼠心肌损伤

Remimazolam alleviates myocardial injury of rats with myocardial ischemia-reperfusion

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