环氧化酶抑制剂对压力超负荷性心肌肥厚大鼠的作用及机制研究  

Effect and Mechanism of Cyclooxygenase Inhibitor on Pressure Overload-induced Cardiac Hypertrophy in Rats

作　　者：王静文 魏明慧 孙浩荣 蒋碧辉 薛明明 WANG Jingwen;WEI Minghui;SUN Haorong(Department of Physiology,College of Basic Medical Sciences,Inner Mongolia Medical University,Inner Mongolia 010030,China)

机构地区：[1]内蒙古医科大学基础医学院生理学教研室,呼和浩特010030

出　　处：《医学研究杂志》2022年第10期56-61,共6页Journal of Medical Research

基　　金：内蒙古自治区科技计划项目(2020GG0238);内蒙古自治区自然科学基金资助项目(2019MS03010);内蒙古自治区科技创新引导项目(KCBJ2018019)。

摘　　要：目的探讨阿司匹林和塞来昔布对压力超负荷性心肌肥厚大鼠的保护作用及机制。方法体内实验:AAC建立压力超负荷性心肌肥厚大鼠模型,阿司匹林和塞来昔布分别灌胃8、10和12周。测量动脉血压和左心室质量指数,超声心动图检测心脏结构和功能变化,免疫组化和qRT-PCR法检测Notch1和Hes1的表达水平。体外实验:机械牵张诱导H9c2心肌细胞肥大,Western blot法检测药物干预后Notch1和Hes1蛋白的表达以及siRNA-Notch1转染后ANP、Notch1和Hes1蛋白的表达水平。结果体内实验:给药后动脉血压和左心室质量指数较模型组降低;与模型组比较,给药10、12周后左心室射血分数、短轴缩短率升高,舒张和收缩末期的左心室内径、容积降低;给药后Notch1和Hes1蛋白和mRNA表达较模型组升高。体外实验:药物干预后Notch1和Hes1蛋白表达较MS组升高;siRNA-Notch1转染后ANP蛋白表达升高,Notch1和Hes1蛋白表达降低。结论阿司匹林和塞来昔布通过上调Notch1信号通路对大鼠压力超负荷性心肌肥厚发挥保护作用。Objective To investigate the protective effect and mechanism of aspirin and celecoxib on pressure overload cardiac hypertrophy in rats.Methods In vivo experiment:the rat model of pressure overload myocardial hypertrophy was established by AAC.Aspirin and celecoxib were administered by gavage for 8 weeks,10 weeks and 12 weeks respectively.Arterial blood pressure and left ventricular mass index were measured.The changes of cardiac structure and function were detected by echocardiography.The expression levels of Notch1 and Hes1 were detected by immunohistochemistry and qRT-PCR.In vitro experiment:mechanical stretch induced hypertrophy of H9c2 cardiomyocytes.The expression levels of Notch1 and Hes1 protein after drug intervention and the expression of ANP,Notch1 and Hes1 proteins after siRNA-Notch1 transfection were detected by Western blot.Results In vivo experiment:after administration,arterial blood pressure and LVMI were lower than those in the model group.Compared with the model group,after 10weeks and 12weeks of administration,the left ventricular ejection fraction and left ventricular shortening fraction increased,and the left ventricular diameter and left ventricular volume decreased at the end of diastole and systole.After administration,the proteins and mRNA expressions of Notch1 and Hes1 were higher than those in the model group.In vitro experiment:after drug intervention,the expression of Notch1 and Hes1 protein were higher than that in MS group.After siRNA-Notch1 transfection,the expression of ANP protein increased and the expression of Notch1 and Hes1 protein decreased.Conclusion Aspirin and celecoxib have protective effects on pressure overload cardiac hypertrophy in rats by upregulating Notch1signaling pathway.

关 键 词：压力超负荷性心肌肥厚 环氧化酶抑制剂 阿司匹林 塞来昔布 Notch1信号通路 

分 类 号：R331[医药卫生—人体生理学]