苯扎贝特对2型糖尿病大鼠胰岛B细胞半胱天冬蛋白酶-3表达的影响

目的观察苯扎贝特对2型糖尿病大鼠胰岛B细胞半胱天冬蛋白酶-3（Caspase-3）表达的影响,探讨其对胰岛B细胞保护的作用机制。方法将46只SD大鼠给予高糖、高脂饲料喂养8周。然后按30 mg·kg^-1剂量腹腔注射0.5%链脲佐菌素（STZ）溶液,建立SD大鼠2型糖尿病模型。总共28只糖尿病大鼠模型建立成功。随即将28只2型糖尿病大鼠按随机数字表法分为2组：糖尿病组（DM组）和糖尿病＋苯扎贝特干预组（DMB组）,每组14只。另取14只SD大鼠作为正常对照组（NC组）。DMB组给予苯扎贝特50 mg·kg^-1·d^-1灌胃,DM组和NC组给予相应容量的蒸馏水灌胃。3组连续灌胃12周。分别测定药物干预前后血清三酰甘油（TG）、总胆固醇（TC）、空腹血糖（FBG）、空腹血清胰岛素（FINS）等指标。干预12周后,处死各组大鼠,采用TUNEL法检测各组大鼠胰岛B细胞凋亡,免疫组化SP法观察胰岛B细胞caspase-3的表达。结果①经苯扎贝特干预后,DMB组大鼠血清TG、TC、FBG水平均较干预前明显下降（均P〈0.05）,而血清FINS水平则较干预前升高（P〈0.05）。②与DM组比较,DMB组大鼠胰岛B细胞凋亡率、胰岛B细胞Caspase-3阳性表达率均明显下降（均P〈0.05）。结论苯扎贝特可下调2型糖尿病大鼠胰岛中Caspase-3表达,发挥抗脂毒性凋亡的作用,从而保护胰岛B细胞功能。

The Experimental Study of Bezafibrate on Caspase-3 Expression of Islet B Cell in Type 2 Diabetic Rats

Objective To observe the effect of bezafibrate on Caspase-3 expression of islet B cell in type-2 diabetic rats and explore the mechanism of protection to islet B cell.Methods Forty-six SD rats were given high sugar and fat feed.After 8 weeks,SD rats were given 30 mg·kg^-1 of 0.5% STZ solution by intraperitoneal injection to make SD rats of type 2 diabetes models.Twenty eight type 2 diabetes models were formed in total.After models were sucessfully formed,then were randomly divided into 2 groups by number table method：diabetes group（DM group） and diabetes with bezafibrate group（DMB group） with 14 rats in each group.The other 14 rats were included as normal group（NC group）,DMB group were treated with bezafibrate（50 mg·kg^-1·d^-1）,DM and NC group were given the same dose of distilled water for 12 weeks.The levels of Triglyceride（TG）,Total cholesterol（TC）,Fasting blood glucose（FBG）,Fasting insulins（FINS） et al were detected before and after the treatment of bezafibrate.After 12 weeks intervention,the apoptosis of islet B cells was detected by TUNEL and the expression of Caspase-3 in islet B cell of rats was detected immunohistochemistry.Results ①The serum levels of TG,TC,and FBG were decreased conspicuously in DMB groups after intervention（all P〈0.05）,the serum levels of FINS was increased（P〈0.05）.②The apoptosis index of islet B cells and expression of Caspase-3 were decreased in DMB group（all P〈0.05）.Conclusion Bezafibrate could downregulate Caspase-3 of islet B cell in type 2 diabetes rats and play a role in anti-liapopotosis of islet B cell to protect islet B cell function.