基于线粒体通透性转换孔调控的脓毒症心肌损伤及普拉克索保护机制的研究

目的: 探究普拉克索能否通过抑制心肌细胞MPTP开放减轻脓毒症大鼠心功能障碍。方法: 将SD大鼠分为假手术组、盲肠结扎穿孔术组(CLP组)、盲肠结扎穿孔术+环孢菌素A组(CsA组)、盲肠结扎穿孔术+普拉克索组(PPX组)。CLP组、CsA组和PPX组统一使用盲肠结扎穿孔术建立脓毒症大鼠模型,其中CsA组静脉注射CsA(2 mg·kg^-1),PPX组予以普拉克索(1 mg·kg^-1)灌胃。观察SD大鼠一般情况、存活率及腹腔解剖情况,超声心动图检测心功能,ELISA法测定血清PCT、NT-proBNP、cTnI水平,通过线粒体肿胀测定MPTP的开放程度,HE染色及电镜观察各组心脏组织病理改变。结果: 术后36 h,假手术组大鼠一般情况、腹腔解剖及心脏病理改变正常,CLP组明显变差,CsA组及PPX组病变程度较CLP组减轻;各组大鼠的存活率:假手术组(100%)＞CsA组(75.0%)＞PPX组(62.5%)＞CLP组(43.8%);CsA组、PPX组心脏左室射血分数均低于假手术组(P＜0.05),均较CLP组升高(P＜0.05);CLP组、CsA组、PPX组血清PCT、NT-proBNP、cTnI水平均高于假手术组(P＜0.05),CsA组、PPX组低于CLP组(P＜0.05);CLP组、CsA组、PPX组心肌细胞MPTP的开放程度大于假手术组(P＜0.05),CsA组、PPX组小于CLP组(P＜0.05)。结论: 心肌细胞MPTP的异常开放是引起大鼠脓毒症心肌损伤的机制之一,普拉克索可以通过抑制心肌细胞MPTP的异常开放减轻脓毒症大鼠的心功能损伤。

Exploration on the pramipexole protects the cardiac function of rats with sepsis by regulating cardiomyocytes mitochondrial permeability transition pore

OBJECTIVE To explore whether pramipexole can alleviate cardiac dysfunction in septic rats by inhibiting the MPTP opening of cardiomyocytes.METHODS Sprague-Dawley rats were divided into sham operation group,cecal ligation and puncture group (CLP group),cecal ligation and puncture model combined with cyclosporine A group (CsA group),cecal ligation and puncture model combined with pramipexole group (PPX group).The CLP group,CsA group and PPX group were uniformly used cecal ligation and puncture to establish a rat model of sepsis.CsA group was injected with CsA (2 mg·kg^-1) intravenously,while PPX group was given pramipexole (1 mg·kg^-1) by gavage.The observed indicators included postoperative infection,cardiac function,myocardial damage,postoperative MPTP opening of myocardial cells,and postoperative cardiac pathological changes.RESULTS Serum PCT levels in CsA group and PPX group were lower than CLP group;the survival rate of rats in each group at 36 hours:sham operation group (100%)>CsA group (75.0%)>PPX group (62.5%)>CLP group (43.8%).The cardiac left ventricular ejection fractions in the CsA group and the PPX group were higher than that in the CLP group (P<0.05),but lower than that in the sham operation group;the serum NT-proBNP level in CsA group and PPX group were lower than that in the CLP group (P<0.05);compared with CLP group,the serum cTnI level in CsA group and PPX group was lower (P<0.05).MPTP opening of cardiomyocytes of rats in each group at 36 hours after operation:the degree of MPTP opening of cardiomyocytes in CLP group,CsA group and PPX group were greater than that in the sham operation group,and the CLP group was greater than that in the CsA group and PPX group (P<0.05).The pathological changes in the hearts of the rats in each group at 36 hours after the operation:the lesions in the CsA group and the PPX group were lighter than those in the CLP group.CONCLUSION The abnormal opening of MPTP in cardiomyocytes is one of the mechanisms that cause myocardial injury in rats with sepsis.Pramipexole can inhibit the abnormal opening of MPTP in cardiomyocytes and reduce the cardiac function damage in septic rats.