Exendin-4对严重烫伤大鼠早期心肌细胞凋亡的影响

Effects of exendin-4 on rat cardiomyocyte apoptosis early after severe scald injury

目的了解exendin-4对烫伤大鼠早期心肌细胞凋亡的作用和机制。方法 54只健康成年SD大鼠,随机分为正常对照组(N组,n=6)、单纯烫伤组(S组,n=24)和烫伤加exendin-4组(E组,n=24)。S组和N组大鼠采用30%TBSAⅢ°烫伤模型,伤后按Parkland公式补液抗休克。E组伤后给予exendin-4。采用DNA切口末端标记法(TUNEL)检测左室心肌细胞凋亡;免疫荧光法检测心肌组织caspase-3活性。结果 S组大鼠于伤后6h,心肌细胞凋亡指数即升高,12h达高峰,48h仍显著高于正常对照组;心肌组织caspase-3活性于伤后6h开始增强,12h达高峰,伤后24h仍显著高于N组。E组较S组,在伤后6、12、24、48h大鼠心肌细胞凋亡指数显著降低(P<0.05),心肌组织caspase-3活性在伤后6、12、24h也显著降低(P<0.05)。统计学分析表明心肌细胞凋亡指数与心肌组织caspase-3活性呈显著正相关(P<0.05)。结论 Exdendin-4可抑制烫伤大鼠早期心肌细胞凋亡,其机制可能是通过抑制心肌组织caspase-3活性,从而抑制心肌细胞凋亡。

Objective To observe the effect of exendin-4 on cardiomyocyte apoptosis in the early stage after scald injury in rats and explore the mechanisms. Methods Fifty-four healthy adult SD rats were randomly divided into normal control group （n=6）, scald group （n=24） and scald with exendin-4 treatment group （n=24）. In the latter two groups, the rats were subjected to 30% TBSA full-thickness scald burns on the back, and Parkland formula was used for determining the resuscitation fluid volume. In exendin-4 treatment group, the rats received intraperitoneal injection of 5 μg/kg exendin-4 after the scald. Apoptosis of the cardiomyocytes from the left ventricle was determined by TUNEL assay and the activity of caspase-3 in the myocardium was assessed. Results In the scald group, the apoptotic index of the cardiomyocytes was increased at 6 h post-burn, reaching the peak level at 12 h, and maintained a significantly higher level than that in the normal control at 48 h （P〈0.05）. Myocardial caspase-3 activity in the scald group was increased at 6 h post-burn and reached the peak at 12 h, still maintaining a high levels at 24 h （P〈0.05）. In exendin-4 treatment group, the apoptotic index of the cardiomyocytes was significantly lower than that in the scald group at 6, 12, 24 and 48 h post-burn （P〈0.05）, and so was the caspase-3 activity at 6, 12 and 48 h （P〈0.05）. A significant positive correlation was found between the apoptotic index of the cardiomyocytes and myocardial caspase-3 activity in the rats （P〈0.05）. Conclusion Exdendin-4 can inhibit rat cardiomyocyte apoptosis early after scald injury possibly by suppressing caspase-3 activity in the myocardium