银杏叶提取物对1型糖尿病心肌病大鼠心肌Bcl-2、Bax和caspase-3表达的影响

目的 探讨银杏叶提取物（extract of Ginkgo biloba,EGB）对1型糖尿病心肌病大鼠心肌Bcl-2、Bax和caspase-3表达的影响.方法 将30只SD雄性大鼠随机分成3组：正常对照组（Con组,n=10）、糖尿病模型组（DM组,n=10）和银杏叶提取物治疗组（EGB组,n=10）.用链脲佐菌素（strepozotocin,STZ）进行腹腔注射,建立1型糖尿病动物模型后用银杏叶提取物注射液腹腔注射建立EGB组,其余两组给予相同体积的生理盐水.于12周末用超声心动图仪测定左心室舒张末期容积（LVIDV）、左心室收缩末期容积（LVISV）、左心室射血分数（LVEF）和每搏射血量（SV）;测定左心室重量指数、血糖和血胰岛素水平;用TUNEL法测定心肌细胞的凋亡指数（AI）;用RT-PCR和Western blot法分别检测其Bcl-2、Bax和caspase-3的表达.结果 与Con组相比,DM组大鼠LVIDV（P ＜0.01）、SV（P ＜0.01）、胰岛素含量（P＜0.01）和心肌组织Bcl-2（P ＜0.05）的表达都显著降低;而左心室重量指数和血糖浓度（P＜0.01）、心肌组织中Bax （P ＜0.05）、caspase-3（P＜0.05）的表达以及Bax/Bcl-2比例均明显升高.当EGB干预治疗后,与DM组相比,大鼠LVIDV（P＜0.05）、SV（P ＜0.05）、胰岛素含量（P＜0.05）和心肌组织Bcl-2（P ＜0.05）的表达均显著升高;而左心室重量指数（P＜0.05）、血糖浓度（P＜0.01）、心肌组织中Bax （P ＜0.05）、caspase-3（P＜0.05）的表达以及Bax/Bcl-2比例（P＜0.05）均明显降低.但是TUNEL染色显示各组大鼠的心肌细胞凋亡率（cardiomyocyte apoptosis index,CAI）没有明显的差异（P＞0.05）.结论 银杏叶提取物可以通过增加Bcl-2的表达,降低Bax、caspase-3表达及Bax/Bcl-2比例,减少心肌细胞的凋亡,从而提高了糖尿病心肌病的心肌功能.这也提示EGB通过调节心肌凋亡相关基因的表达,减少细胞的凋亡是其治疗糖尿病心肌病的重要机制之一.

Effects of Extract of Ginkgo Biloba on Myocardial Bcl-2, Bax and Caspase-3 Expression in Type 1 Diabetic Cardiomyopathy Rats

Objective To study the effect of extract of Ginkgo biloba （EGB） on myocardial Bcl-2、Bax and caspase-3 expression in type 1 diabetic cardiomyopathy rats.Methods Thirty male SD rats were randomly divided into three groups：normal control group （Con）,diabetic group（DM） and EGB-treated group（EGB）,with each group of ten only.Streptozotocin（STZ） was injected intraperitoneally to the animals in later two groups to induce type 1 diabetic rats model and the EGB-treated group rats were injected intraperitoneally with EGB,and the same volume of normal saline was injected to the other groups.At the end of the 12th week,we used echocardiography to determine the left ventricular end-diastolic volume （LVIDV）,the left ventricular end-systolic volume （LVISV）,the left ventricular ejection fraction （LVEF） and the stroke volume （SV）.The left ventricle weight index 、blood glucose and blood insulin were measured.Myocardial apoptosis was measured by two ways.The one was terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling （TUNEL） and the other was the expressions of Bcl-2,Bax and caspase-3 of Left ventricular tissue,which were measured by Western blot and RT-PCR respectively.Results Compared to Con group,LVIDV （P ＜ 0.01）,SV （P ＜ 0.01）,blood insulin （P ＜0.05） and the Bcl-2 （P ＜ 0.05） of ventricular tissue were decreased in diabetic group,while the left ventricle weight index （P ＜ 0.01）,blood glucose（P ＜ 0.01）,the Bax （P ＜ 0.05）,caspase-3 （P ＜ 0.05） and Bax/Bcl-2 were increased.After the EGB intervention,compared to DM group,LVIDV （P ＜ 0.05）,SV （P ＜ 0.05）,blood insulin （P ＜ 0.05） and the Bcl-2 （P ＜ 0.05） of ventricular tissue were increased,while the left ventricle weight index（P ＜ 0.05）,blood glucose（P ＜ 0.01）,the Bax （P ＜ 0.05）,caspase-3 （P ＜0.05） and Bax/Bcl-2 （P ＜ 0.05） were decreased,but cardiomyocyte apoptosis index （CAI） showed no significant difference between each