妊娠期糖尿病大鼠胰腺组织中GRP78、TRAF2、Caspase-12蛋白的表达
Detection of expressions of GRP78,TRAF2,and Caspase-12 in pancreatic tissue of gestational diabetes mellitus rats

目的:探讨内质网应激(ERS)及肿瘤坏死因子受体相关因子2(TRAF2)、Caspase-12与妊娠期糖尿病(GDM)的关系。方法:60只健康雌性SD大鼠随机分为4组:高脂高糖饮食受孕组(HP)、高脂高糖饮食未孕组(HV)、普通饮食受孕组(NP)、普通饮食未孕组(NV),分别给予相应处理。测定妊娠末期空腹血糖(FBG)、空腹胰岛素(FINS)、血脂,并计算胰岛素抵抗指数(HOMA-IR),采用HE染色观察胰腺组织形态学改变,TUNEL法检测胰岛细胞凋亡指数(AI),免疫组化法测定GRP78表达,Western blot法测定TRAF2、Caspase-12蛋白表达。结果:妊娠和高脂高糖饮食均可使大鼠FBG、FINS、HOMA-IR和血脂升高,二者具有协同作用(P＜0.05)。妊娠第21天时,HP组胰岛出现不同程度萎缩,细胞数量明显减少,可见核固缩和核裂解; 妊娠、高脂高糖饮食均可导致大鼠胰腺组织中GRP78、TRAF2、Caspase-12表达升高,并且二者具有协同效应(P＜0.05)。结论:妊娠和高脂高糖饮食均参与了ERS,ERS可能通过TRAF2-Caspase-12信号通路诱导胰岛细胞凋亡,继而参与GDM的发生发展。
Aim: To investigate the relationship of endoplasmic reticulum stress,TRAF2,Caspase-12 and the gestational diabetes mellitus(GDM).Methods: A total of 60 healthy female SD rats were randomly allocated into four groups: pregnant group with high fat and sugar diet(HP),virgin group with high fat and sugar diet(HV),pregnant group with normal diet(NP),virgin group with normal diet(NV).Fasting blood glucose(FBG),fasting serum insulin(FINS),and blood lipid of each group were tested in the late pregnancy, then the insulin resistance index(HOMA-IR)was calculated.The morpholog ical changes in pancreatic tissue were observed using HE staining,the apoptosis of islet cells was detected by TUNEL,and the expression of GRP78 was tested by immunohistochemistry, the expressions of TRAF2 and Caspase-12 were tested by Western blot.Results: Pregnancy and high fat and sugar diet could increase FBG,FINS,HOMA-IR,blood lipid synergistically(P＜0.05).At the 21st day during pregnancy, pancreatic tissue appeared different degree of atrophy,islet cells decreased significantly,pyknosis and karyorrhexis could be seen in HP group. Pregnancy, high fat and high sugar diet were the main factors for increasing the GRP78, TRAF2, Caspase-12 expressions in rat pancreatic tissue, and they had synergistic effect(P＜0.05).Conclusion: Pregnancy and high fat and sugar diet are involved in ERS; ERS might be involved in the development of GDM through inducing islet cell apoptosis by TRAF2-Caspase-12 signaling pathway