糖尿病小鼠胰岛β细胞结构的光镜和电镜研究

The Structure of Pancreatic Islet β Cells in Diabetic Mice by LM and TEM

目的观察2型糖尿病模型db/db小鼠胰岛β细胞的超微结构、胰岛素表达及数量变化,探讨β细胞的病理改变与2型糖尿病病因的关系。方法分别选取3、5、8月龄尾静脉空腹血糖高于10.1mmol/L,且肥胖的db/db自发性糖尿病小鼠,每组8只,作为糖尿病组;选取相应年龄段尾静脉空腹血糖低于6.0mmol/L,体重正常的db/+m表型正常小鼠,每组8只,作为对照组。于相应年龄段取胰尾,用于透射电镜观察、免疫组织化学观察和图像分析。结果电镜下随病情进展,db/db小鼠胰岛β细胞内的分泌颗粒数量明显减少,有的细胞甚至缺如,致密芯电子密度降低,β细胞可见凋亡的早期改变以及细胞核和细胞器的病理改变,细胞间髓样小体增多。免疫组织化学显示同月龄糖尿病组小鼠胰岛β细胞阳性率和胰岛素蛋白平均光密度值(OD值)低于相应对照组(p<0.05),且随着病程的进展,db/db小鼠胰岛β细胞阳性率和胰岛素表达呈现递减趋势(p<0.05)。结论2型糖尿病β细胞的超微结构遭到破坏,引起β细胞合成分泌胰岛素障碍和数量减少,与2型糖尿病病情的轻重有关,反映了2型糖尿病病程不同阶段的病机特点。

Objective To observe and analyze the ultrastructure and insulin expression changes in pancreatic islet beta cells of spontaneous db/db diabetic mice as the disease developed, and explore their relationship with pathogeny of type 2 diabetes mellitus（T2DM）. Methods 3, 5, 8 month-old obese db/db mice with fasting blood glueose（FBG）more than 10.0mmol/L were selected（24mice）, the age-matched normal weight db/＋m mice with FBG less than 6.0mmol/L as the control group（24mice）. The tails of pancreas were excised and observed by light microscope （LM） and transmission electron microscope （TEM）. Results The number of secretory granules in beta cell cytoplasm of db/db mouse was significantly decreased or absent, and the electron-density of dense core in the secretory granule decreased as well, with early apoptosis and pathologic changes of nucleus and organelles and increased myelin-bodies between insular cells. The positive rates of beta cells and optical density average（OD） of insulin positive cells were significantly decreased in diabetic mice than in control mice（p 〈 0.05）, with the decreased trend as the progress of the spontaneous diabetes. Conclusion The ultrastnwtural and quantitative changes of pancreatic islet beta cells in db/db diabetic mice cause synthesis and secretion dysfunction of insulin, which is related to the degree and different stages of 2-type diabetes mellitus.