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钙敏感受体参与黄芪甲苷对心肌缺血再灌注损伤的保护作用 被引量:12

Calcium-sensing receptor contributes to the protective effect of astragaloside IV on myocardial ischemia reperfusion injury
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摘要 目的探讨黄芪甲苷对心肌缺血再灌注损伤的保护作用及其可能的机制。方法 48只SD大鼠随机分为假手术组、缺血组、黄芪甲苷低剂量组(20 mg·kg^(-1))、黄芪甲苷中剂量组(40 mg·kg^(-1))、黄芪甲苷高剂量组(80 mg·kg^(-1))和黄芪甲苷(80 mg·kg^(-1))+calindol组。采用冠状动脉结扎法建立大鼠心肌缺血再灌注损伤模型。氯化硝基四氮唑蓝(NBT)染色观察心肌梗死面积;TUNEL染色评价心肌细胞凋亡;酶联免疫吸附法测定血清中CK-MB和c Tn I含量;免疫组化法测定钙敏感受体(Ca SR)表达,电泳法测定bcl-2,bax蛋白表达。结果黄芪甲苷(40,80 mg·kg^(-1))可不同程度的降低心肌梗死面积,抑制血清CK-MB和c Tn I的释放,减轻心肌细胞凋亡,降低心肌组织Ca SR蛋白表达,抑制bax蛋白表达,增加bcl-2蛋白表达。进一步研究显示,黄芪甲苷对心肌缺血再灌注损伤的这种保护作用可被Ca SR激动剂calindol部分抑制。结论黄芪甲苷对缺血心肌再灌注损伤具有一定的保护作用,其机制可能通过下调Ca SR通路,抑制细胞凋亡有关。 Objective To investigate the protective effect of astragaloside IV( As IV) on myocardial ischemia reperfusion( M I/R) injury and the underlying mechanism. Methods 48 SD rats w ere randomly divided into 6 groups: sham operation group,myocardial ischemia-reperfusion group,As IV( 20 mg·kg^-1) group,As IV( 40 mg·kg^-1) group,As IV( 80 mg·kg^-1) group and As IV( 80 mg·kg^-1) + calindol( 3. 5 mg·kg^-1) group.Ischemia w as produced by ligating the left anterior descending coronary artery( LAD). M yocardial infarct size w as determined by NBT staining technique and a digital imaging system; the content of CK-M B and c Tn I in serum w ere determined by ELISA; the expression of Ca SR w as determined by immunohistochemistry;bax and bcl-2 protein expression w ere determined by w estern blot. Results Pretreatment of As IV( 40,80 mg·kg^-1) before MI/R could decrease the infracted size,the content of CK-MB and c Tn I,Ca SR and bax protein expressions,and increase the bcl-2 protein expressions. In addition,the effects of As IV w ere partly abolished by Ca SR agonist calindol. Conclusions As IV pretreatment could attenuate MI/R injury through the inhibition of the Ca SR signaling pathw ay,and subsequent cardiomyocytes apoptosis.
作者 王佳 高迪迪 王文慧 戴竣宇 杨洋 侯续伟 WANG Jia;GAO Didi;WANG Wenhui;DAI Junyu;YANG Yang;HOU Xuwei(Basic Medical School, Jinzhou Medical University, Jinzhou 121000, China)
出处 《沈阳药科大学学报》 CAS CSCD 北大核心 2018年第4期312-318,共7页 Journal of Shenyang Pharmaceutical University
基金 辽宁省大学生创新创业训练计划项目(201610160000040) 辽宁省自然科学基金资助项目(201602284)
关键词 黄芪甲苷 心肌缺血再灌注损伤 钙敏感受体 凋亡 AsIV myocardial ischemia/reperfusion calcium-sensing receptor apoptosis
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