胰岛素受体亚型改变及相关通路活化在糖尿病小鼠肠上皮细胞过度增殖中的作用  

MEK / ERK pathway activated by changing insulin receptor isoform is associated with abnormal proliferation of intestinal epithelial cells in diabetic mice

作　　者：欧阳慧[1] 夏忠胜[1] 杨洪生[1] 于涛[1] 卢锡基 许稷豪 陈其奎[1] 

机构地区：[1]中山大学孙逸仙纪念医院消化内科,广东广州510120

出　　处：《中国病理生理杂志》2016年第5期874-879,共6页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81370475)

摘　　要：目的:探讨胰岛素受体亚型改变及其相关下游通路活化情况在糖尿病小鼠肠上皮细胞异常增殖中的作用。方法:用腹腔注射链脲霉素的方法制作糖尿病小鼠模型,采用增殖细胞核抗原标记法比较糖尿病小鼠及对照组小鼠肠上皮细胞的增殖情况。利用RT-PCR法测定胰岛素受体亚型表达比例在2组中的差异。采用realtime PCR及Western blot法分别从mRNA和蛋白质水平检测2组之间胰岛素受体相关通路各分子MEK1/2、ERK1/2、PI3K以及Akt的表达情况。结果:糖尿病组小鼠的小肠上皮细胞增殖指数显著升高(P<0.05),且细胞中胰岛素受体亚型IR-A/IR-B的比值也明显升高(P<0.05)。糖尿病小鼠肠上皮细胞中MEK1、MEK2和ERK1/2的mRNA水平及磷酸化蛋白水平均高于对照组(P<0.05)。结论:糖尿病小鼠肠上皮细胞过度增殖可能与其中胰岛素受体亚型IR-A/IR-B的比值增高及其相关MEK/ERK通路的激活有关。AIM： To investigate the role of insulin receptor（ IR）-A/IR-B ratio and the downstream pathway in abnormal proliferation of intestinal epithelial cells（ IECs） in diabetic mice. METHODS： Diabetes mouse models were induced by intraperitoneal streptozocin injection. The proliferating cell nuclear antigen（ PCNA） proliferation rates in the small intestine tissue were evaluated by immunohistochemical methods. The expression of IR isoforms was detected by RTPCR. To ensure that the downstream pathways of IR are involved,real-time PCR and Western blot were performed to detect the expression of MEK1 /2,ERK1 /2,PI3 K and Akt. RESULTS： In diabetic mice,the PCNA proliferation rates were higher than those in control group（ P〈0. 05）,and a high ratio of IR-A / IR-B was detected in the IECs（ P〈0. 05）. The mRNA expression of MEK1,MEK2,ERK1 /2 and their phosphorylated protein levels in the diabetic mice were significantly higher than those in control group（ P〈0. 05）. CONCLUSION： The over-proliferation of IECs in the diabetic mice is associated with high IR-A / IR-B ratio and up-regulation of IR / MEK / ERK pathway.

关 键 词：糖尿病 肠上皮细胞 胰岛素受体 细胞增殖 

分 类 号：R363[医药卫生—病理学]