庚醇/甘草次酸对大鼠心肌缺氧复氧再灌注细胞凋亡的影响

Effect of heptanol or 18α-glycyrrhetinic acid on ischemia-reperfusion apoptosis in isolated rat hearts

目的:研究细胞间隙连接通讯(GJIC)抑制剂庚醇/甘草次酸可否减少大鼠心肌缺氧复氧再灌注诱发的心肌细胞凋亡,探讨心肌GJIC在心肌细胞凋亡中的作用。方法:制作Langendorf心脏灌流模型,随机分为正常灌注(SO)组、缺氧复氧再灌注(IR)组、缺氧复氧再灌注庚醇(HT)组和缺氧复氧再灌注甘草次酸(GA)组。于整体缺氧30min再灌注2h末测定心肌梗死面积,应用脱氧核糖核苷酸末端转移酶介导的缺口末端标记(TUNEL)技术检测心肌细胞凋亡;于整体缺氧30min末用改良的划痕标记染料示踪技术测定心肌GJIC。结果:与SO组相比,IR组心肌梗死面积和凋亡细胞数明显增加,但GJIC无明显变化。与IR组比较,HT组和GA组心肌梗死面积和凋亡细胞数显著减少,伴GJIC明显受抑。结论:缺氧复氧再灌注所诱发的心肌细胞凋亡与心肌GJIC密切相关,GJIC抑制剂庚醇/甘草次酸可减少心肌细胞凋亡,进而防止心肌缺氧复氧再灌注损伤。

Objective：To examine the effects of heptanol or 18α-glycyrrhetinic acid on myocardial cell apoptosis of ischemia-reperfusion injury and the role of gap junctional intercellular eommunication（GJIC） during the process of eadiocyte apoptosis.Methods：Isolated buffer-perfused rat hearts （n=70）were divided randomly into four groups,normal perfusion （SO）group,myocardial ischemia-reperfusion （IR）group,IR treated with heptanol（HT） group and IR treated with 18α-glycyrrhetinic acid （GA）group.The effect of HT or GA on cardiocyte apoptosis was detected with terminal-deoxynueleotidyl transferase mediated nick end labeling （TUNEL） at the end of 2 hours＇ reperfusion,and then the GJIC at the end of 30 minutes of myocardial ischemia was measured with modified Scrape-loading and dye transfer method.Results：Compared with SO group,IR group showed bigger infarct size and higher number of cardiocyte apoptosis after 2h reperfusion,but the GJIC was not inhibited at the end of 30 minutes of ischemia.Compared with IR group,HT or GA resulted in smaller infarct size and lower number of apoptosis and the GJIC was significantly reduced.Conclusion：The apoptosis of myocardial is- chemia-reperfusion injury was related to GJIC and gap junctional inhibitor HT or GA could alleviate apoptosis by reducing the GJIC during isehemia.