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目的选择GK大鼠为2型糖尿病模型,研究噻唑烷二酮类药物(TZDs)罗格列酮和吡格列酮对胰岛B细胞保护作用的机制。方法以雄性GK大鼠和正常对照雄性Wistar大鼠为研究对象,随机分为4组:Wistar正常对照组13只(W组),GK+罗格列酮组10只(R组),GK+吡格列酮组10只(P组)和GK未治疗组10只(G组)。其中罗格列酮组给予罗格列酮钠2mg.kg-1.d-1灌胃,吡格列酮组给予吡格列酮3mg.kg-1.d-1灌胃,GK未治疗组不予药物干预,实验为期6周。实验结束后,取胰腺标本固定并进行电镜观察。同时采用免疫组化法检测胰岛细胞Bcl-2和Bax蛋白的表达,并采用TUNEL法检测胰腺B细胞凋亡情况。结果电镜下,G组大鼠胰岛B细胞出现核皱缩,核仁消失,染色质边集,呈现凋亡早期改变;其他3组胰岛未见凋亡改变(P<0.01)。R组和P组的Bcl-2表达显著高于G组(P<0.01);W组与G组相比差异无统计学意义。R组、P组和W组的Bax表达低于G组(P<0.05);R组和P组间差异无统计学意义。结论 GK大鼠胰岛B细胞存在细胞凋亡,可能与其发生糖尿病有关。罗格列酮和吡格列酮可以减少GK大鼠胰岛B细胞凋亡,且与Bcl-2、Bax表达变化有关。
Objective To investigate the mechanism of the protective effects of rosiglitazone and pioglitazone on pancreatic islet B cells of GK rats, a model of type 2 diabetes mellitus (T2DM). Methods Male Wistar rats were divided into 4 groups randomly: male Wistar control group (W group), GK + rosiglitazone group (R group), GK + pioglitazone group 10 (P group) and 10 GK untreated group (G group). Rosiglitazone group was given rosiglitazone sodium 2mg.kg-1.d-1 gavage, pioglitazone group was given pioglitazone 3mg.kg-1.d-1 gavage, GK untreated group without drug intervention, the experiment For 6 weeks. After the experiment, take the pancreas specimens fixed and electron microscopy. Immunohistochemistry was used to detect the expression of Bcl-2 and Bax in pancreatic islet cells. The apoptosis of B cells in pancreatic was detected by TUNEL method. Results Under electron microscope, the nuclear islet shrinkage, nucleolus disappeared, and the chromatin marginal set appeared in the G group. The apoptotic cells were observed in the other three groups (P <0.01). The expression of Bcl-2 in R group and P group was significantly higher than that in G group (P <0.01). There was no significant difference between W group and G group. The expression of Bax in R group, P group and W group was lower than that in G group (P <0.05). There was no significant difference between R group and P group. Conclusion The apoptosis of islet B cells in GK rats may be related to the occurrence of diabetes. Rosiglitazone and pioglitazone can reduce the apoptosis of islet B cells in GK rats, which is related to the changes of Bcl-2 and Bax expression.