庚醇和甘草次酸对大鼠心肌致死性再灌注损伤的保护作用

The protective effects of heptanol and 18α-glycyrrhetinic acid on ischemia and reperfusion injury in isolated rat hearts

目的:研究缺血前给予庚醇和甘草次酸能否预防大鼠心肌致死性再灌注损伤,包括心肌细胞坏死和凋亡,并观察其对心律失常的影响。方法:制作Langendorf心脏灌流模型,随机分为正常灌注组(SO)、缺血再灌注组(IR)、庚醇组(HT)和甘草次酸组(GA)。于整体缺血30min后再灌注2h。应用四氮硝基唑蓝(nitroblue tetraxolium,NBT)测定心肌梗死面积,脱氧核糖核苷酸末端转移酶介导的缺口末端标记法(terminal-deoxynucleotidyl transferase mediated nick end labeling,TUNEL)检测心肌细胞凋亡,Curtis和Walker心律失常评分系统评价心律失常严重程度。结果:与SO组相比,IR组心律失常评分增加(0.26±0.5对2.86±1.46);心肌梗死范围明显扩大,凋亡细胞数显著增加(0.35±0.26)%对(35±6.6)%,P<0.01。与IR组比较,HT和GA组心肌梗死面积明显减轻,分别为(38±9.7)%对(9±2.9)%对(16±7.0)%,P<0.05;凋亡细胞数也显著减少,分别为(35±6.6)%对(17±4.6)%对(22±1.2)%,但心律失常发生无明显减少或增加。结论:缺血前给予间隙连接抑制剂庚醇和甘草次酸可明显减轻心肌致死性再灌注损伤,表现为缩小心肌梗死范围和减少心肌细胞凋亡,但对心律失常的发生无影响。

Objective.. The aim of the study is to examine the effects of pretreatment with heptanol and 18α-glycyrrhetinic acid on lethal reperfusion injury., necrosis and apoptosis, and on the ar- rhythmias during myocardial ischemia and reperfusion in isolated rat heart. Methods.. Isolated buffer-perfused rat hearts were divided randomly into four groups, normal perfusion group（SO）, myocardial ischemia and reperfusion group（IR）, heptanol group（HT） and 18α-glycyrrhetinic acid group （GA）. The effect of HT and GA on cardiocyte necrosis was detected by nitroblue tetraxolium and apoptosis by terminal -deoxynucleotidyl transferase mediated nick end labeling at the end of 2h reperfusion, and the reperfusion arrhythmias was evaluated by an arrhythmias scoring systerm by Curtis and Walker. Results.. Compared with SO group, IR group showed larger infarct size, higher number of cardiocyte apoptosis（0. 35 ± 0.26）% vs. （35 ± 6.6）% and severe arrhythmias（0.26 ± 0. 5 vs. 2.86± 1.46,P〈0.01）after 2h reperfusion. Compared with IR group, HT and GA resulted in smaller infarct size[（38±9.7）% vs. （9±2.9）% vs. （16±7.0）%, P〈0.05）]and lower number of ap-optosis[-（35±6.6）% vs. （17±4.6）%0 vs. （22±1.2） %, P〈0.05）], but the arrhythmias was not affected. Conclusion： These results suggest gap junctional inhibitor HT and GA can alleviate lethalrn-yocardial reperfusion injury including myocardial cell necrosis and apoptosis, but do not affect the arrhythmias.