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

作　　者：甄磊[1] 张懿兰 王晓娜 张小琼[2] ZHEN Lei;ZHANG Yilan;WANG Xiaona;ZHANG Xiaoqiong(Department of Anesthesiology,the Second Hospital of Baoding,Baoding 071000,China;Second Department of Cardiology,the Second Hospital of Baoding,Baoding 071000,China)

机构地区：[1]保定市第二医院麻醉科,河北保定071000 [2]保定市第二医院心内二科,河北保定071000

出　　处：《基础医学与临床》2024年第9期1243-1248,共6页Basic and Clinical Medicine

基　　金：保定市科技计划项目(2041ZF206)。

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。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.

关 键 词：心肌缺血/再灌注 心肌损伤 瑞马唑仑 Hippo/Yes相关蛋白 

分 类 号：R614[医药卫生—麻醉学]