硫唑嘌呤预处理对大鼠心肌缺血再灌注损伤的作用及机制的研究

Effect and mechanism of azathioprine pretreatment on myocardial ischemia reperfusion injury in rats

目的:探讨硫唑嘌呤对心肌缺血再灌注损伤的保护作用及机制。方法:SD大鼠随机分为模型组、硫唑嘌呤组和假手术组,测定三组大鼠心肌梗死面积,电镜观察心肌组织形态学变化,全自动生化分析仪检测大鼠血清中c TnⅠ、CK-MB含量,比色法检测血清MDA水平及SOD、MPO活性,ELISA法检测炎症因子TNF-α、IL-6水平,Western blot及免疫组化法检测心肌组织TLR4表达情况。结果:与模型组比较,硫唑嘌呤组大鼠心肌梗死面积明显减小;心肌细胞水肿坏死状况改善; c TnⅠ、CK-MB含量降低; SOD活性升高、MPO活性降低; MDA、TNF-α和IL-6水平下降; TLR4表达显著下调(P<0. 01)。结论:硫唑嘌呤在缺血再灌注损伤时,能抑制炎症反应,减轻氧化应激,且其保护机制可能与下调TLR4信号通路有关。

Objective:To investigate the protective effect and mechanism of azathioprine on myocardial ischemia reperfusion injury.Methods:SD rats were randomly divided into model group,azathioprine group and sham operation group.Then we observed the size of myocardial infarct,and myocardial morphological changes by electron microscopy.The level of cTnⅠand CK-MB were measured by automated biochemical analyzer.The expression of MDA and activity of SOD,MPO were determined by colorimetric detection.The inflammatory factors of TNF-αand IL-6 were measured by ELISA,and protein of TLR4 by Western blot and immunohistochemistry.Results:Compared with the model group,azathioprine pretreatment significantly decreased myocardial infarct size,improved the edema and necrosis of the myocardial cells,decreased the contents of cTnⅠand CK-MB,enhanced activity of SOD,reduced activity of MPO and levels of MDA,TNF-αand IL-6,and down-regulated the expression of TLR4 expression(P<0.01).Conclusion:Azathioprine can inhibit inflammatory response and reduce oxidative stress during ischemia-reperfusion injury,and its protective mechanism may be related to the down-regulation of TLR4 signaling pathway.