丙泊酚通过抑制线粒体途径的细胞凋亡保护心肌缺血再灌注损伤(英文)

Propofol protects hearts from ischemia-reperfusion injury through interfering with mitochondria-dependent apoptotic pathway

目的观察丙泊酚对离体大鼠心肌缺血再灌注(I-R)损伤的影响,并从线粒体过氧化损伤方面探讨其可能的作用机制。方法应用Langendorff离体心脏灌流系统,全心停灌25 min,再灌注30 min建立心肌I-R损伤模型。记录各项心功能指标;测定心肌线粒体呼吸链的完整性、膜肿胀度和丙二醛(MDA)含量;流式细胞术检测心肌细胞凋亡率及Bcl-2和Bax蛋白的表达,免疫组化法测定半胱氨酸天冬氨酸蛋白酶(caspase)-3,-9和-8的表达。结果与I-R组相比,缺血前10 min开始,并于再灌注期间持续灌流丙泊酚30和60μmol·L^(-1)能明显改善I- R后的心功能;心肌线粒体呼吸链损伤有所恢复,膜肿胀度减轻,MDA生成明显减少,心肌细胞凋亡率明显降低,Bcl-2表达增加,Bax表达减少,caspase-3和caspase-9阳性细胞数明显减少。结论丙泊酚减轻I-R所致的心肌线粒体过氧化损伤,抑制线粒体途径的细胞凋亡。

AIM To investigate the protective effect of propofol on ischemia-reperfusion （I-R） injury in isolated rat hearts and clarify the possible molecular mechanism from oxidative stress and the apoptosis initiated by mitochondria pathway. METHODS The isolated Langendorff-perfused rat hearts were rendered globally ischemia for 25-min followed by 30-min reperfusion to establish I-R injury model. The cardiac function parameters were recorded. The swelling, integrity of electron transport chain （ETC） and content of malond- ialdehyde （MDA） in myocardium mitochondria were determined. The percentage of apoptotic cardiomyocytes and the expressions of Bcl-2 and Bax proteins were evaluated by flow cytometry. The expressions of caspases-8, -9 and -3 proteins in myocytes were detected by immunohistochemistry. RESULTS Compared with I-R group, perfusing with 30 and 60 μmol· L^- propofol from 10 min before ischemia to whole reperfusion period resulted in improvement in cardiac function. The swelling and ETC lesion of mitochondria alleviated, and MDA content decreased. The percentage of apoptotic cardiomyocytes was markedly lower than that of I-R group. The expression of Bcl-2 protein was higher and the expression of Bax was lower than that of I-R group. The expressions of caspase-3 and caspase-9 proteins were obviously lower than those in I-R group. CONCLUSION Propofol confers significant protection against the I-R injury in the isolated rat hearts. Diminishing oxidative stress, protecting mitochondria from peroxidative injury, thus interfering with the mito-chondria-dependent apoptotic pathway may be one of the major mechanisms of its cardioprotection.