氯氨酮对大鼠心肌缺血再灌注心肌细胞凋亡和Fas蛋白、Bcl-2蛋白表达的影响

目的:探讨氯胺酮作用下大鼠实验性心肌缺血再灌注时心肌细胞凋亡与Fas及Bcl-2蛋白表达的变化及与心肌组织损伤的关系,并分析心肌组织病理学损伤程度。方法:以穿线结扎或松扎左冠状动脉制备大鼠心肌缺血再灌注模型。32只大鼠随机分成假手术组(假手术4.5 h)、缺血再灌注组(缺血30min、再灌注4 h)、低剂量氯胺酮+缺血再灌注组(缺血30min、再灌注4h)及高剂量氯胺酮+缺血再灌注组(缺血30min、再灌注个4 h)。以缺口末端标记法检测心肌细胞凋亡的变化,S-P免疫组化法分别检测Fas与Bcl-2蛋白水平变化,做病理组织切片检查心肌损伤情况。结果:心肌缺血再灌注后心肌细胞凋亡指数及Fas蛋白阳性染色指数与Bcl-2蛋白阳性染色指数均增加,氯氨酮可减少心肌凋亡,减少Fas和Bcl-2蛋白阳性细胞表达;心肌缺血再灌注后心肌组织呈大小不一的灶性坏死,坏死周围有炎性细胞浸润,氯胺酮作用后坏死减轻,低剂量氯胺酮作用更明显。结论:心肌缺血再灌注时心肌细胞凋亡、Fas基因的蛋白与Bcl-2蛋白表达量均增加,氯氨酮可减少心肌凋亡,减少细胞Fas和Bcl-2蛋白阳性表达,从而减轻心肌损伤,且低剂量氯氨酮作用更明显。

Effects of Ketamine on Apoptosis and Expression of Fas and Bcl-2 Protein in Rats with Experimental Myocardial ischemia/reperfusion injury

Objective: To investigate Effects of ketamine(KTM) on apoptosis and expression of Fas and Bcl-2 protein in a rat model of myocardial ischemia/reperfusion injury,and analysis histopathological injury of myocardial.Methods: Rat models with MIR were established by occluding left coronary artery(LCA) and followed by release of it with ligation.Thirty two rats were divided randomly into sham group(sham operated for 4.5h),MIR group(30min of ischemia followed by 4h of reperfusion), KTM 2mg/kg +MIR group and KTM 4mg/kg +MIR group.Terminal deoxynucleotidy transferase mediated dUTP fluorescein nick end labeling(TUNEL) and S-P immunohistochemical staining were used respectively to detect the changes of apoptosis and protein expression of Fas and Bcl-2 protein,and Histopathological changes in myocardium was also observed.Results: Apoptotic index(AI) and positive index(PI) of Fas protein and Bcl-2 protein in myocytes were increased in myocardium with MIR,Fas/Bcl-2 is also increased.Local myocyte necrosis and inflammatory cell infiltration around infarcted area were observed in myocardium with MIR,the injury was less in groups with KTM,and the least in group with KTM 2mg/kg.Conclusions: The increase of mentioned parameters suggests that apoptosis and Fas and Bcl-2 system are involved in the process of MIR injury,KTM could attenuate the apoptosis and expression of Fas and Bcl-2 protein and Fas/Bcl-2, so it could attenuate the injury of myocardium and the lower dose of KIM have more obvious effect.