硫化氢对糖尿病大鼠心肌损伤保护作用及其抗凋亡机制

摘要

目的观察硫化氢( H2 S)对糖尿病大鼠心肌损伤的保护作用及其抗凋亡机制。方法雄性SD大鼠随机分为正常对照组( NC 组)、糖尿病对照组( DM 组)、硫氢化钠( NaHS)治疗组( NaHS+DM组)和NaHS对照组( NaHS组)。采用链脲佐菌素(STZ)55 mg/kg腹腔注射诱导糖尿病大鼠模型,造模成功8周后行离体心脏灌流,测定左心室动力学指标；电镜观察心肌细胞超微结构改变；采用分光光度法检测心肌组织Caspase-3的活性；RT-PCR检测左心室心尖组织Bcl-2、Bax mRNA的表达。结果与NC组相比,NaHS 组各项指标差异均无统计学意义( P>0.05),而DM组左心室发展压( LVDP)、左心室内压最大上升速率和下降速率(依dp/dtmax)均明显降低(P0.05) . However, compared with NC group, in diabetic rats, left ventricular developed pressure ( LVDP) , maxi-mal rise/fall rate of left ventricular pressure ( ±dp/dtmax) were decreased (P<0.01), left ventricular end dias-tolic pressure (LVEDP) was increased (P<0.01). The activity of Caspase-3 was increased(P<0.01), while the ratio of Bcl-2/Bax at mRNA level was decreased(P<0.01). The degeneration of myocardiac myofibrillae and ede-ma of mitochondria were shown in diabetic rats. Compared with DM group, the hemodynamic parameters were re-served , and the injury of myocardiac myofibrillae and mitochondria was attentuated when the diabetic rats were trea-ted with NaHS at 14 μmol/(kg·d). Caspase-3 activity was also decreased (P<0.01), and the ratio of Bcl-2/Bax at mRNA level was increased (P<0.01). Conclusion H2S can protect myocardium in diabetic rats, may be related to suppressing the happening of cell apoptosis.