摘要
目的:分析远隔缺血时不同适应渐进模式对心肌缺血再灌注损伤大鼠心肌的保护作用及其机制。方法:采用大鼠在体心肌缺血-再灌注损伤模型,并应用随机抽签法将60只实验大鼠随机分为假手术组、缺血/再灌注对照组、标准机械后适应组、标准远隔时适应组、正向渐进模式远隔时适应组、负向渐进模式远隔时适应组六组,每组10只。同时采用称重法检测实验大鼠心肌梗死范围,TUNEL法检测细胞凋亡,分光光度计测线粒体通透性转换孔道(MPTP)开放程度,并应用蛋白印迹分析检测心肌细胞内单克隆抗体信号传导及转录活化因子3(p-STAT3)、单克隆抗体JAK激酶2(p-JAK2)、蛋白激酶B单克隆抗体(p-AKT)、单克隆抗体信号调节蛋白激酶1/2(p-ERK1/2)蛋白表达情况,比较各组实验结果。结果:与缺血/再灌注对照组相比,标准机械后适应组、标准远隔时适应组、正向渐进模式远隔时适应组、负向渐进模式远隔时适应组的心肌梗死范围、心肌细胞凋亡率明显更低,MPTP开放程度明显更低;且正向渐进模式远隔时适应组心肌梗死范围、心肌细胞凋亡率明显低于其他组,MPTP开放程度明显低于其他组(P<0.05)。蛋白印迹检测显示,正向渐进模式远隔时适应组的p-STAT3、p-JAK2、p-AKT、p-ERK1/2表达较假手术组外的其他组显著提高(P<0.05)。结论:正向渐进远隔时适应模式可以发挥较传统标准模式更好的心肌保护作用,其作用机制可能与激活再灌注损伤补救激酶(RISK)和生存活化因子增强(SAFE)途径,抑制MPTP开放有关。
Objective:To analyze the protective effect and mechanism of different adaptive progressive models in distant ischemia on myocardial ischemia-reperfusion injury in rats.Methods:In vivo myocardial ischemia-reperfusion injury model was used,and 60 experimental rats were randomly divided into 6 groups:sham operation group,ischemia/reperfusion control group,standard mechanical post adaptation group,standard distant time adaptation group,positive progressive mode distant time adaptation group and negative progressive mode distant time adaptation group,with 10 rats in each group.At the same time,the myocardial infarction range of experimental rats was detected by weighing method,the apoptosis was detected by TUNEL method,the opening degree of MPTP was measured by spectrophotometer,and the protein expression of p-STAT3,p-JAK2,p-AKT and p-ERK1/2 in cardiomyocytes was detected by Western blot analysis.The experimental results of each group were compared.Results:Compared with the ischemia/reperfusion control group,the myocardial infarction area,myocardial cell apoptosis rate and MPTP opening degree of the standard mechanical post adaptation group,the standard remote adaptation group,the positive progressive mode remote adaptation group and the negative progressive mode remote adaptation group were significantly lower;the myocardial infarction area and myocardial cellapoptosis rate in the adaptation group were significantly lower than those in other groups in positive progressive distant time adaptation mode,and the opening degree of MPTP was significantly lower than those in other groups(P<0.05).Western blot showed that the expressions of p-STAT3,p-JAK2,p-AKT and p-ERK1/2 in the adaptation group were significantly higher than those outside the sham operation groups(P<0.05).Conclusion:The positive progressive distant adaptation mode can play a bettermyocardial protective effect than the traditional standard mode,and its mechanism may be related to the activation of RISK and SAFE pathways and the inhibition of MPTP opening.
作者
张国明
丁立成
孙广峰
留志贤
王斌
孙媛媛
ZHANG Guo-ming;DING Li-cheng;SUN Guang-feng;LIU Zhi-xian;WANG Bin;SUN Yuan-yuan(Cardiovascular Hospital Affiliated to Xiamen University,Fujian,Xiamen361009)
出处
《实用中西医结合临床》
2022年第6期7-10,14,共5页
Practical Clinical Journal of Integrated Traditional Chinese and Western Medicine
基金
福建省厦门市科技局惠民项目(编号:3502Z20194075)
福建省自然科学基金面上项目(编号:2018D00205)。