瞬时受体电位锚蛋白亚型1受体在远端创伤预处理保护心肌缺血/再灌注损伤中的作用

Role of transient receptor potential ankyrin 1 receptor in remote preconditioning of trauma-induced cardioprotection against myocardial ischemia-reperfusion injury

目的探讨瞬时受体电位锚蛋白亚型1受体(transient receptor potential ankyrin 1,TRPA1)在远端创伤预处理(RPCT)保护心肌缺血/再灌注(MI/R)损伤中的作用及相关机制。方法将SD大鼠随机分为5组:假手术组(Sham)、模型组(IR)、远端创伤预处理组(RPCT)、TRPA1抑制剂+远端创伤预处理组(TCS+RPCT)和TRPA1抑制剂组(TCS)。实验采用大鼠心肌缺血/再灌注模型,全程监测血流动力学。再灌注完成后留取大鼠心脏,测量心肌梗死面积和心肌细胞凋亡水平,检测线粒体醛脱氢酶2(ALDH2)活性和蛋白表达以及4-羟基壬烯醛(4-HNE)的表达水平。结果与Sham组相比,IR组心肌梗死面积和心肌凋亡细胞增加,ALDH2活性和表达降低,4-HNE含量升高;与IR组相比,RPCT组心肌梗死面积和心肌凋亡细胞减少,ALDH2活性和表达升高,4-HNE含量降低;TCS+RPCT组相比于RPCT组,RPCT的心肌保护作用消失。结论TRPA1受体介导了远端创伤预处理减轻大鼠心肌缺血/再灌注损伤的作用,其机制可能与调控ALDH2活性和蛋白表达,影响4-HNE含量有关。

Aim To investigate the role of transient receptor potential ankyrin 1 receptor in remote preconditioning of trauma-induced cardioprotection against myocardial ischemia-reperfusion injury and related mechanism.Methods SD rats were randomly divided into five groups:Sham operation group(Sham),model group(IR),remote preconditioning of trauma group(RPCT),TRPA1 inhibitor+remote preconditioning of trauma group(TCS+RPCT)and TRPA1 inhibitor group(TCS).The model of myocardial ischemia/reperfusion in rats was established,and the hemodynamics was monitored throughout the process.After reperfusion,the rat heart was taken to measure the myocardial infarction area and myocardial apoptosis rate,the activity and protein expression of mitochondrial aldehyde dehydrogenase 2(ALDH2)and the expression of 4-hydroxynonenal(4-HNE)were detected.Results Compared with sham group,myocardial infarction area and myocardial apoptosis cell increased.Meanwhile,the activity and expression of ALDH2 decreased and the production of 4-HNE increased in IR group.However,compared with IR group,RPCT group had decreased myocardial infarction area and the rate of cardiomyocyte apoptosis,the activity and expression of ALDH2 increased,the production of 4-HNE decreased.And then,compared with RPCT group,TCS+RPCT group reduced the myocardial protective effect of remote preconditioning of trauma.Conclusions TRPA1 receptor mediates the effect of remote preconditioning of trauma alleviating myocardial ischemia/reperfusion injury in rats.Its mechanism may be related to regulating ALDH2 activity and protein expression,and affecting the content of 4-HNE.