摘要
目的探讨丹参酮ⅡA(TA)对心肌缺血-再灌注损伤(MIRI)的影响及其对Janus激酶2(JAK2)/信号转导和转录激活因子3(STAT3)通路的影响。方法建立老年大鼠MIRI模型和心肌细胞缺氧/复氧损伤(HRI)模型,分别从体内和体外水平进行研究。采用超声心动图测定心功能,应用全自动生化检测仪检测大鼠血清肌酸激酶(CK)、乳酸脱氢酶(LDH)。四甲基偶氮唑盐微量酶反应比色法(MTT)检测细胞活力,TUNEL法检测细胞凋亡,DCFH-DA荧光探针检测活性氧(ROS)含量,全自动生化检测仪检测细胞上清液丙二醛(MDA)和超氧化物歧化酶(SOD)水平,免疫印迹法(Western Blotting)检测相关蛋白表达水平。应用JAK2/STAT3抑制剂AG490干预心肌细胞,观察各项指标变化。结果TA可改善MIRI大鼠心肌梗死面积、心脏射血分数和缩短分数、血清CK和LDH水平(P<0.05),改善HRI心肌细胞活力和凋亡水平(P<0.05),提高HRI心肌细胞抗氧化能力,改善ROS、MDA和SOD水平(P<0.05)。Western Blotting检测结果显示,TA可改善p-JAK2、p-STAT3、Bcl-2/Bax比值、cleaved Caspase-3水平(P<0.05),AG490干预可逆转上述指标变化(P<0.05)。结论TA对MIRI具有一定保护作用,可能通过激活JAK2/STAT3通路减少心肌细胞凋亡从而改善MIRI。
Objective To investigate the effect of tanshinoneⅡA(TA)on myocardial ischemia-reperfusion injury(MIRI)and Janus kinase 2/signal transduction and activator of transcription 3(JAK2/STAT3)pathway.Methods The MIRI model and myocardial cell hypoxia/reoxygenation injury(HRI)model of aged rats were established and studied respectively in vitro and in vivo.The cardiac function was detected by echocardiography.Serum creatine kinase(CK)and lactate dehydrogenase(LDH)were detected by automatic biochemical detector.Cell viability was detected by methyl thiazolyl tetrazolium(MTT)method.Cell apoptosis was detected by TUNEL method.Reactive oxygen species(ROS)content was detected by DCFH-DA fluorescence.Automatic biochemical detector was used to detect MDA and SOD in cell supernatant.The expression of related proteins was detected by Western Blotting.JAK2/STAT3 inhibitor AG490 was used to intervene myocardial cells.Results TA significantly reduced myocardial infarction area,increased ejection fraction,and reduced the levels of CK and LDH in MIRI rats(P<0.05).TA significantly improved the activity and apoptosis of myocardial cells in HRI(P<0.05).TA improved the antioxidant capacity of HRI cardiomyocytes,and ROS,MDA and SOD(P<0.05).Western Blotting showed that p-JAK2,p-STAT3,Bcl-2/Bax ratio and cleaved Caspase-3 improved(P<0.05).AG490 intervention could reverse the changes of the indexes(P<0.05).Conclusion TA could improve IRI by activating JAK2/STAT3 pathway to reduce cardiomyocyte apoptosis.
作者
王煜
WANG Yu(940 Hospital of PLA Joint Logistic Support Force,Lanzhou 730050,Gansu,China)
出处
《中西医结合心脑血管病杂志》
2021年第8期1290-1296,共7页
Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease
