摘要
目的采用D-半乳糖加高脂高糖乳剂及链脲佐菌素(STZ)构建类似老年人糖尿病的大鼠动物模型,观察其胰腺形态学变化。方法选用健康Wistar雌性大鼠,20只灌胃生理盐水为正常对照组;20只采用腹腔注射D-半乳糖40d为衰老模型组;另25只则采用腹腔注射D-半乳糖40d并灌胃高脂高糖乳剂30d后腹腔注射STZ(体重≤200g按30mg/kg,体重>200g者按体表面积进行计算),制备衰老糖尿病模型大鼠,筛选空腹血糖≥11.1mmol/L者为成模鼠,上述各组大鼠再继续灌胃生理盐水10d后,各组随机取10个样本以免疫组化、光镜和电镜分别观察大鼠胰岛诱导型一氧化氮合酶(iNOS)表达、胰腺细胞凋亡、胰岛形态及胰岛细胞和腺泡细胞超微结构变化。结果衰老模型组大鼠胰岛iNOS表达量和胰腺细胞凋亡数较正常对照组增加,衰老糖尿病模型组胰岛iNOS表达量和胰腺细胞凋亡数剧增达3倍以上。HE染色显示,衰老模型组胰岛数量、面积仅为正常的50%～70%,衰老糖尿病模型组胰岛数量、面积仅为正常的20%～30%,且岛内中心部细胞(β细胞)消失尤为显著。电镜观察显示,衰老糖尿病模型组大鼠胰腺细胞明显脱颗粒,呈现膜性结构皱缩,核染色质固缩、碎裂等细胞凋亡征象。结论采用腹腔注射D-半乳糖加高脂高糖乳剂及腹腔注射STZ,胰腺形态组织学证实大鼠在衰老模型基础上胰岛β、D细胞数量进一步下降可引发糖尿病。
Objective To observe the variances in morphology of the rat model similar to aged human diabetes mellitus （DM）.Methods Healthy female Wistar rats were chosen.20 rats were intragastric administrated with physiological saline to build the normal control group;20 rats were intraperitoneal injected with D-galactose for 40 days to set up the aged model group;and 25 rats were intraperitoneal injected with D-galactose for 40 days,intragastric administrated with enriched diet for 30 days since injection with D-galactose 11 days,then intraperitoneal injected with low dose streptozotocin （STZ） to construct the aged DM model group.Rats whose full blood sugar （FBG） ≥11.1 mmol/L were chosen as successful aged DM rats.After intragastric administrating all rats with physiological saline for 10 days,10 rats were selected from each group to detect inducing nitric-oxide synthase （iNOS） expression in pancreatic island by immunohistochemistry ABC method,detect pancreatic gland apoptosis by TUNEL,and observe the change of hist-morph and ultrastructure of pancreatic gland by light microscope and electron microscope.Results Contrasted with the normal control group,the amount of iNOS expression of pancreatic island and pancreatic gland apoptosis in the aged model group increased.HE staining manifested the amount and area of pancreatic island in the aged model group was only 50%～70% of that of the normal control group,and the deprivation of cells in the center of pancreatic island was especially predominant.The observation of electron microscope manifested the cells of rats′ pancreas in the aged DM model group obviously degranulated.Conclusions The adopt of intraperitoneal injection with D-galactose,intragastric administration with enriched diet,and then intraperitoneal injection with STZ can produce the increase of apoptosis and/or cell death of iNOS and βcell in pancreatic island,which leading to degression of function and quantity ofβcell in pancreatic islet and successfully building the aged DM rats model which is similar to the old people DM best.
出处
《中国老年学杂志》
CAS
CSCD
北大核心
2010年第15期2132-2136,共5页
Chinese Journal of Gerontology
基金
2006福建中医学院中西医结合研究院陈可冀发展基金会研究课题(CKJ2006006)
2008年福建中医学院中西医结合研究院陈可冀发展基金会研究课题(CKJ2008040)
2008年福建中医学院校管课题(X2007016)
福建省教育厅F5类项目(2008F5028)
