高、低剂量极化液对缺血/再灌注心肌细胞凋亡及相关基因的影响

目的 :探讨高、低两种剂量葡萄糖 -胰岛素 -钾极化液 （GIK）对缺血 /再灌注 （MI/R）心肌超微结构 ,细胞凋亡及其相关基因的影响。方法 :制备兔MI/R模型 ,分别用生理盐水 ,低剂量极化液 （LGIK） ,高剂量极化液 （HGIK）干预分组。检验心肌组织SOD活性 ,原位末端标记 （TUNEL）法测定凋亡心肌细胞 ,免疫组化SP法测定Bcl 2 ,Fas的含量 ,在电镜下观察心肌细胞的超微结构。结果 :与对照组比较 ,HGIK组SOD活性增加 （P <0 .0 1） ,凋亡指数 （AI）和Fas含量减少 （P <0 .0 1） ,Bcl 2含量增加 （P <0 .0 1）。心肌细胞超微结构表现为损伤减轻。LGIK亦可增加SOD活性和Bcl 2含量 （P <0 .0 5 ） ,减少AI和Fas（P <0 .0 5 ）含量。结论 :GIK具有抗缺血 /再灌注损伤的作用 ,其机制可能是通过调节Bcl 2和Fas介导的心肌缺血 /再灌注细胞凋亡而实现。高剂量GIK对缺血 /再灌注心肌细胞的保护作用显著大于低剂量GIK（P <0 .0 5 ）。

Comparative study of the effects of high dose and low dose GIK on cardiomyocyte apoptosis and apoptosis related genes during myocardial ischemic and reperfusion

AIM: To study the effect of different doses of gl ucose-insulin-potassium (GIK) cocktail on cardiac myocyte apoptosis and ultrastructure following myocardial ischemia/reperfusion (MI/R). METHODS: Rabbits were subject ed to 45 min myocardial ischemia, followed by reperfusion for 3 h. Anesthetized rabbits were randomly treated with continuous infusion of saline, LGIK (100 g/L Glucose,20 U/L Insulin and 20 mmol/L KCl), HGIK (300 g/L Glucose, 50 U/L Insulin and 80 mmol/L KCl), 5 min before the reperfusion and throughout the 3 h reperfusion. The animals were sacrificed and the heart was harvested for SOD and ultrastructure examination(electron microscope). Apoptosis was identified by TUNEL and apoptosis index (AI)was obtained. The expressions of Fas,Bcl-2 protein were measured by immunohistochemical technique. SOD was assayed spectrophocometrically and myocardial ultrastructure was examined. RESULTS: Compared with the v ehicle treated rabbits, the HGIK-treated rabbits showed protection against MI/R injury as evidenced by marked decrease of AI and the content of Fas protein (P<0.01), significantly increased the content of Bcl-2 protein and activity of SOD(P<0.01). The ultrastructure of myocardium showed attenuated injury. AI and the content of Fas protein of the LGIK-treated rabbits were reduced (P<0.05), and the content of Bcl-2 protein and activity of SOD were improved(P<0.05). CONCLUSION: G IK can protect myocardium from MI/R injury by modulating the expressions of Fas and Bcl-2 protein and inhibit apoptosis following myocardial MI/R and the high dose of GIK play a more important role in protecting myocardial ischemia reperfusion than that of the low dose of GIK.