苯扎贝特对2型糖尿病大鼠胰岛β细胞半胱天冬蛋白酶-3表达的影响

The experimental study of Bezafibrate on caspase-3 expression of βcell in type 2 diabetic rats

目的观察苯扎贝特对2型糖尿病大鼠胰岛β细胞半胱天冬蛋白酶-3(caspase-3)表达的影响,探讨其对胰岛β细胞保护的作用机制。方法采用高糖高脂饲料喂养加小剂量链脲佐菌素建立SD大鼠2型糖尿病模型,28只成模的糖尿病大鼠随机分为糖尿病组(DM,n=14)和糖尿病+苯扎贝特干预组(DMB,n=14),另设正常对照组(NC,n=14)。DMB组给予每日苯扎贝特50mg/kg剂量灌胃,DM组和NC组予相应容量的蒸馏水灌胃,连续灌胃12周。测定大鼠药物干预前后的TG、TC、FBG、FINS指标。干预12周后处死所有大鼠,取胰腺组织HE染色镜下观察,TUNEL法检测胰岛β细胞凋亡情况,免疫组化法观察胰岛β细胞caspase-3的表达。结果 (1)经苯扎贝特干预后,DMB组血TG、TC较前明显下降(P<0.01),FBG也下降(P<0.05),而FINS则较前升高(P<0.05)。(2)与DM组相比,DMB组大鼠胰岛β细胞凋亡减少(P<0.05),caspase-3表达也减少(P<0.05)。结论苯扎贝特可以改善糖尿病大鼠糖脂代谢紊乱,进一步减轻胰岛素抵抗及改善胰岛分泌功能,其作用机制可能与下调胰岛caspase-3表达,减少胰岛β细胞凋亡有关。

Objective To observe the effect of Bezafibrate on caspase-3 expression of βcell in type-2 diabetic rats and the mechanism of protection toβcell.Methods We adopted injecting Sprague-Dawley rats with low dose STZ after high calorie to make type 2 diabetes.28 type 2 diabetes models were formed,there were divided into diabetes rats with bezafibrate group（DMB,n=14） and Diabetes group（DM,n=14）.Normalgroup（NC,n=14）were included,DMB group were treated with bezafibrate（50mg/kg） everday,DM and NC group were given the same dose of distilled water.The levels of Triglyceride（TG）,Total cholesterol（TC）,Fasting blood glucose（FBG）,Fasting insulins（FINs） were detected before and after the treatment of bezafibrate respectively.After 12 weeks intervention.Pancreas were dyed with Hematoxylin-Eosin,the morphous of pancreas islet were observed by microscope,the apoptosis of cells was detected by TUNEL,the expression of caspase-3 in islets of rats was detected by immunohistochemistry.Results（1）The levels of TG,TC were decreased conspicuously in DMB groups after intervention（P〈0.01）,the levels of FBG was also decreased,the levels of FINS was increased（P〈0.05）;（2）The apoptosis index ofβ-cells and expression of caspase-3 was decreased in DMB group（P〈0.05）.Conclusion Intervening hyperlipemia with Bezafibrate could reduce the resistance of iusulin and improve the secretary function of βcell,was associated with decreasing expression of caspase-3 and apoptosis of βcell to the protection of βcell.