摘要
目的:心肌缺血再灌注损伤是一种多因素参与的复杂病理过程,涉及多个环节。氧自由基和炎性因子的产生与心肌缺血再灌注损伤有关。炎症反应(包括白细胞的浸润、炎性细胞因子及炎症介质的释放)在心肌缺血再灌注损伤中具有重要作用。本研究旨在探讨大黄素对缺血再灌注损伤心肌的保护作用及对抗炎症反应的可能机制。
方法:选择中国小型猪12头,随机分为三组,分别为对照组、CVD组(卡维地洛)、大黄素组。用球囊堵塞法制作缺血再灌注动物模型。TTC染色观察心肌梗死范围的变化及左心室射血分数(EF)的变化。检测I/R前、I/R2h及I/R6h血清CK-MB及cTnI的变化。检测I/R前、I/R2h及I/R6h时血清补体C_3、TNF-α、IL-6及IFN-r的变化。Western blot法检测I/R6h时心肌HSP60的表达。TUNEL染色检测心肌细胞凋亡。免疫组化染色检测心肌MCP-1的表达变化。
结果:本研究证实大黄素可明显缩小I/R后心肌梗死范围,保护和改善心肌功能,其作用与CVD相似,与对照组比较,有显著性差异(P<0.05)。大黄素可显著抑制I/R时补体C_3的激活和消耗,降低TNF-α、IFN-r的水平,其程度与CVD相似,与对照组比较有显著性差异(P<0.05)。大黄素还能抑制MCP-1及HSP-60的表达,与对照组比较有显著性差异(P<0.05)。与CVD比较,两者作用相似,无统计学差异。
结论:上述结果说明大黄素可明显抑制I/R时补体的激活、炎症介质的释放及炎症反应所致的心肌细胞损伤,抑制心肌细胞凋亡,从而保护心肌细胞的结构和功能,其作用与CVD相似。
Object:Myocardial ischemia-reperfusion injury is a complex multi-factor involved in the pathological process involves a number of links.Oxygen free radicals and the generation of inflammatory factors and myocardial ischemia-reperfusion injury.Inflammatory response(including leukocyte infiltration,inflammatory cytokines and the release of inflammatory mediators) in myocardial ischemia-reperfusion injury plays an important role.This study was designed to investigate the effect of emodin on myocardial ischemia-reperfusion injury and protective effect against the possible mechanism of inflammatory response.
Methods:Choice of 12 Chinese miniature pigs were divided into three groups,namely control group,CVD group(carvedilol),emodin group.Balloon method used to plug animal model of ischemia-reperfusion.TTC staining of the scope of the changes in myocardial infarction and left ventricular ejection fraction(EF) changes.Detection of I / R before,I/R2h and I/R6h serum CK-MB and cTnI changes.Detection of I / R before,I/R2h and I/R6h serum, IL-6 and IFN-r changes.Western blot assay I/R6h complement C3, TNF-αand expression of myocardial HSP60.TUNEL staining of cardiomyocyte apoptosis.Immunohistochemical staining of myocardial MCP-1 expression.
Result:This study confirmed that emodin can significantly reduce the I / R myocardial infarction after the scope of the protection and improvement of myocardial function,similar to its role and CVD, compared with the control group,the difference was significant(P <0.05).Emodin significantly inhibited I / R when the complement C3 activation and consumption,,IFN-r level,the degree of similarity with CVD,compared with reducing TNF-αthe control group were significantly different(P<0.05).Emodin also inhibited MCP-1 and HSP-60 expression,compared with the control group were significantly different(P <0.05).With CVD compared to the role of similarity between the two,no statistical difference.
Conclusion:The above results show that emodin significantly inhibited I / R when the complement activation,the release of inflammatory mediators and the inflammatory response induced myocardial cell injury,inhibition of cardiomyocyte apoptosis, thereby protecting myocardial structure and function of cells, similar to its role and CVD.
引文
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