Na^+/H^+交换体抑制剂HOE-642在大鼠心肺复苏应用中的保护作用及其机制

Protective effect and mechanism of Na^+/H^+ exchange inhibitor HOE-642 in rat cardiopulmonary resuscitatin

目的探讨Na^+/H^+交换体抑制剂HOE-642在大鼠心肺复苏(CPR)应用中的保护作用及其机制。方法建立大鼠窒息性心跳骤停与复苏模型,并将24只SD大鼠采用随机数字表法分为对照组(S组)、单纯药物组(S+H组)、损伤组(N组)和HOE-642组(N+H组)四组,每组6只。各组大鼠在接受不同处理后,检测脑组织线粒体通透性转换孔(mPTP)开放程度、线粒体功能及氧化应激水平、脑组织病理学评价及CPR后脑缺血再灌注损伤标记物。结果与S组和S+H组相比,N+H组脑组织mPTP开放程度、细胞凋亡标志物水平、氧化应激产物水平、脑缺血再灌注损伤标记物含量及线粒体复合物功能差异无统计学意义(P>0.01)。与N组相比,N+H组脑组织mPTP开放程度、细胞凋亡标志物水平、氧化应激产物水平以及脑缺血再灌注损伤标记物含量均显著下降(P<0.01);与N组相比,N+H组线粒体复合物功能显著升高(P<0.01)。结论在心跳骤停后CPR时联合使用HOE-642能显著降低mPTP的开放程度,改善脑细胞线粒体复合物的功能,促进能量代谢恢复,并减轻脑组织缺血再灌注损伤,减少细胞凋亡和脑细胞变性坏死的发生。

Objective To explore the protective effect and mechanism of Na+/H+ exchange inhibitor HOE-642 in cardiopulmonary resuscitation (CPR) in rats.Methods The suffocating cardiac arrest and resuscitation model was establish tin rats.24 SD rats were divided into the control group (group S),single drug group (group S+H),injury group (N group) and HOE-642 group (N+H group).After receiving different treatments,the opening level of mitochondrial permeability transition pore (mPTP),the function of mitochondria and the level of oxidative stress,the pathological evaluation of brain tissue and specific marker of ischemia-reperfusion injury after CPR were detected in each group.Results Compared with N group,the degree of openness of mPTP,the levels of apoptotic markers,the productions of oxidative stress and the content of specific marker of cerebral ischemia-reperfusion injury were significantly decreased in N+H group (P<0.01).Compared with N group,the functions of mitochondrial complexes in N+H group increased significantly(P<0.01).Conclusion The combined use of HOE-642 in CPR after cardiac arrest could apparently reduce the opening of mPTP,improve the functions of mitochondria complexes in brain cells,promote the recovery of energy metabolism,alleviate the cerebral ischemia-reperfusion injury and reduce the occurrence of apoptosis and necrosis in brain cells.