左旋卡尼汀对兔缺血/再灌注心肌细胞凋亡的影响

Protective effects of carnitine against myocyte apoptosis following myocardial ischemia/reperfusion in rabbits

目的观察左旋卡尼汀对心肌缺血/再灌注(MI/R)后心肌细胞凋亡的影响,探讨其保护作用的机制.方法制备家兔MI/R模型,缺血45min,再灌注3h.25只家兔随机分为三组对照组(Ⅰ组,n=5),MI/R组(Ⅱ组,n=10),左旋卡尼汀治疗组(Ⅲ组,n=10)在缺血后5min静脉注射左旋卡尼汀[1.5mL/(kg·h)].再灌注结束后检测心肌组织SOD活性,原位末端标记(TUNEL)法测定凋亡心肌细胞,免疫组化法测定凋亡相关基因bcl-2,fas的表达.结果MI/R造成明显的心脏功能障碍,缺血区细胞凋亡.SOD活性明显升高,凋亡指数(AI)和Fas含量减少(P<0.05),Bcl-2含量明显升高(P<0.05).结论左旋卡尼汀具有抗缺血再灌注后心肌损伤的作用,其机制可能是通过调节Bcl-2和Fas介导的细胞凋亡而实现.

AIM： To study the protective effects of carnitine on cardiac myocyte apoptosis following myocardial ischemia/reperfusion （MI/R）. METItODS： Rabbits were subjected to 45-min myocardial ischemia followed by reperfusion for 3 h. Anesthetized rabbits were randomly divided into 3 group： control group （ n = 5 ）, in which left anterior descending coronary artery was exposed and a piece of silk thread was placed around the artery but not tied, MI/R group （n = 10）, in which normal saline 1.5 mL was injected into sublingual vein after MI, and carnitine group （ n = 10 ）, in which carnitine 1.5 mL/（ kg · h） was given intravenously 5 min after MI. The animals were sacrificed and their hearts were harvested. Apoptosis was identified by TUNEL and apoptosis index （AI） was obtained. The expression of Fas and Bcl-2 protein was measured by immunohistochemical technique. RESULTS： MI/R caused significant cardiac dysfunction and myocardial death. Compared with the MI/R group, the carnitine group had better protection against MI/R injury, as shown by marked decrease of AI and the average A value of Fas protein, as well as significantly improved the average A value of Bcl-2 protein. CONCLUSION： Carnitine can protect myocardium from MI/R injury by modulating the expression of Fas and Bcl-2 protein and inhibiting apoptosis following myocardial MI/R.