罗格列酮对2型糖尿病大鼠心肌细胞凋亡及其基因表达的影响

目的　观察 2型糖尿病大鼠心肌细胞凋亡率、凋亡调控基因Bax、Bcl-2的表达变化及罗格列酮的干预作用。方法　8周龄SD大鼠高热量饮食一月后 ,腹腔注射小剂量链脲佐菌素 (STZ 3 0mg/kg) ,成模后分别于 12、2 4周宰杀动物 ,采用光镜、原位末端标记法、流式细胞术检测心肌细胞凋亡及心肌Bax、Bcl -2表达水平。结果　糖尿病大鼠心肌凋亡细胞数明显增多 ,Bax蛋白表达显著上调 ,Bax/Bcl-2比值增加 (P均 <0 0 1) ,Bcl -2蛋白表达有所下降 ,但无统计学意义。罗格列酮干预组凋亡率降低 (P <0 0 1) ,升高的Bax蛋白表达下调 ,降低的Bcl -2蛋白表达上调 ,但与糖尿病未治疗组均无统计学差异 (P >0 0 5 )。结论　心肌细胞凋亡在糖尿病大鼠心肌病变进程中起一定作用 ,罗格列酮可抑制心肌细胞凋亡 ,但与Bax、Bcl -2的调控关系不大。

The Effects of Rosiglitazone on Cardiomyocyte Apoptosis and Expression of Bax and Bcl-2 in Type 2 Diabetic Rats

Objective To investigate the effects of rosiglitazone on the cardiomyocyte apoptosis and expression of Bax and Bcl-2 in type 2 diabetic rats. Methods 8 weeks old SD rats were feeded with high calorie for one month, and then were intraperitoneally injected with a low dose of STZ (30mg/kg). The diabetic and control rats were killed at the 12th and 24th weeks after establishing model, respectively. Cardiomyocyte apoptosis was evaluated by TUNEL and flow cytometry. Flow cytometry was also used to detect the protein expression of Bax and Bcl-2. Results Compared with control group, apoptotic cells number, the Bax expression level and Bax/Bcl-2 ratio significantly increased in the diabetic rat hearts (P<0.001). Bcl-2 expression level in the diabetic rat hearts was lower than that in control rat heart, but the difference between the two groups was not statistically significant. After rosiglitazone treatment, apoptotic rate of cardiomyocyte in the diabetic rats significantly decreased(P<0.01), and Bax expression level decreased, and Bcl-2 expression level increased, but the difference in the level of Bax and Bcl-2 expression between the diabetic rats with or without treatment was not significant. Conclusion Cardiomyocyte apoptosis may play a role in the pathological lesion of diabetic myocardium. Cardiomyocyte apoptosis in diabetic rats could be partially inhibited by rosiglitazone, which was not related with Bax and Bcl-2.