川芎嗪与黄芪甲苷配伍对小鼠离体心脏缺血再灌注损伤的保护作用及机制研究  

Protective Effects of Tetramethylpyrazine Combining Astragaloside against Myocardial Ischemia Reperfusion Injury in Mice

作　　者：李玉梅[1] 杨辛欣[1] 曲盛 刁元元 刘仲康 鲍慧玮[1] 张大方[1] 王楚盈[1] LI Yumei;YANG Xinxin;QU Sheng;DIAO Yuanyuan;LIU Zhongkang;BAO Huiwei;ZHANG Dafang;WANG Chuying(Changchun University of Traditional Chinese Medicine,Pharmacy College,Changchun 130117 Jilin,China)

机构地区：[1]长春中医药大学药学院

出　　处：《中药新药与临床药理》2019年第12期1454-1458,共5页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：国家自然基金项目（81173597）;吉林省卫生计生青年科研课题（2014Q046）;吉林省教育厅“十三·五”科学技术项目（JJKH20190455KJ）;吉林省卫生计生青年科技骨干培养计划项目（2016Q052）;吉林省中医药科技项目（2017005）

摘　　要：目的研究川芎嗪与黄芪甲苷配伍对小鼠离体心脏缺血再灌注损伤(MIRI)的保护作用及作用机制。方法将50只雄性C57BL/6小鼠分为空白对照组、模型组、川芎嗪组(TMP,200 mmol·L^-1)、黄芪甲苷组(ASG-IV,100 mmol·L^-1)及川芎嗪(200 mmol·L^-1)+黄芪甲苷(100 mmol·L^-1)组,通过用Langendorff灌流系统缺血30 min、再灌注40 min制备小鼠离体心脏MIRI模型,记录心率(HR)、左心室发展压(LVDP)和左室内压最大变化速率(±dp/dtmax),收集冠脉流出液,测定冠脉流出液中谷草转氨酶(AST)、乳酸脱氢酶(LDH)、肌酸激酶(CK)含量。以蛋白免疫印迹法(Western Blot)检测心肌线粒体Txnip、NLRP3、IL^-1β蛋白的表达。结果与模型组相比,川芎嗪与黄芪甲苷配伍组可明显上调LVDP、+dp/dtmax,下调-dp/dtmax(均P<0.05),改善心功能;川芎嗪与黄芪甲苷配伍组可减少LDH的释放(P<0.01),降低心肌酶AST、CK的活性(P<0.05);同时,川芎嗪与黄芪甲苷配伍组能减少NLRP3(P<0.01)和Txnip(P<0.05)的表达,减少NLRP3炎性体。结论川芎嗪与黄芪甲苷配伍可减轻小鼠离体心脏缺血再灌注损伤,其机制与Txnip/NLRP3信号通路有关。Objective To study the protective effect and mechanism of Tetramethylpyrazine combining Astragaloside on the myocardial ischemia reperfusion injury in isolated C57 BL/6 mice hearts.Methods Fifty adult male C57 BL/6 mice were randomly divided into five groups:control group,ischemia-reperfusion group(MIRI group),Tetramethylpyrazine group(TMP,200 mmol·L^-1),Astragaloside group(ASG-IV,100 mmol·L^-1)and compatibility of TMP(200 mmol·L^-1)and ASG-IV(100 mmol·L^-1)group.The isolated mice heart ischemia-reperfusion models were established by Langendorff perfusion device,with ischemia for 30 min and reperfusion for 40 min.The heart rate(HR),the left ventricular developed pressure(LVDP)and the maximum change rate of left ventricular pressure(±dp/dtmax)were recorded,and the levels of lactic dehydrogenase(LDH),creatine kinase(CK),Aspartate transaminase(AST)in coronary effluent were detected.Western Blot was used to observe the expression of proteins Txnip,NLRP3 and IL^-1β.Results Compared with IR group,TMP+ASG-IV can significantly increase LVDP,+dp/dtmax,and decrease-dp/dtmax(P<0.05);decrease the levels of LDH,CK,AST in coronary effluent(P<0.01,P<0.05,P<0.05),and the expression levels of proteins Txnip,NLRP3(P<0.05,P<0.01).Conclusion Tetramethylpyrazine combined Astragaloside-IV alleviated the ischemia-reperfusion injury of isolated mice hearts,which might be related to activating Txnip/NLRP3 signaling pathway.

关 键 词：川芎嗪 黄芪甲苷 配伍 心肌缺血再灌注 Txnip/NLRP3信号通路 

分 类 号：R285.5[医药卫生—中药学]