6种2型糖尿病动物模型中生化和病理改变的比较  

Comparison of biochemical and pathological changes in six type 2 diabetic animal models

作　　者：裴天仙[1] 郭景玥[1] 王春雨 滕晋莹 张洲 徐义涵 郭传敏[1] 张金晓[1] 胡金芳[1] PEI Tianxian;GUO Jingyue;WANG Chunyu;TENG Jinying;ZHANG Zhou;XU Yihan;GUO Chuanmin;ZHANG Jinxiao;HU Jinfang(TIPR Drug Assessment Co.Ltd,Tianjin 300462,China)

机构地区：[1]天津药物研究院新药评价有限公司,天津300462

出　　处：《药物评价研究》2020年第9期1740-1746,共7页Drug Evaluation Research

基　　金：国家科技重大新药创制项目(2015ZX09501004)。

摘　　要：目的比较6种常见2型糖尿病动物模型的生化指标和胰岛、肝脏的组织病理学改变。方法大鼠、小鼠各32只,随机分为8组:大鼠对照组、大鼠高脂高糖+四氧嘧啶组、大鼠高脂高糖+链脲佐菌素组、ZDF大鼠组、小鼠对照组、db/db小鼠组、ob/ob小鼠组和KK-ay小鼠组。制备2型糖尿病模型:高脂高糖+四氧嘧啶组和高脂高糖+链脲佐菌素组,喂饲高脂高糖饲料6周后,分别ip 1次150 mg/kg剂量的四氧嘧啶和30 mg/kg的链脲佐菌素,ZDF大鼠饲喂Purina#5008饲料6周;C57BL、db/db和ob/ob小鼠普通饲料、KK-ay小鼠高脂料喂养8周。每周测定体质量;腹主动脉取血,全自动生化分析仪测定血清空腹血糖(FBG)、胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL)和高密度脂蛋白胆固醇(HDL),Elisa法检测血清中空腹胰岛素(FINS)水平。剖取胰腺、肝脏进行HE染色,于光学显微镜下观察组织病理学变化。结果与对照组比较,高脂高糖+四氧嘧啶及高脂高糖+链脲佐菌素组大鼠体质量增长幅度更大;ZDF大鼠组体质量缓慢降低;血脂、血糖和胰岛素测定结果显示,与大鼠对照组比较,高脂高糖+四氧嘧啶组和高脂高糖+链脲佐菌素组FBG、TC、TG均显著升高(P<0.01),FINS显著降低(P<0.01);ZDF大鼠组FBG、TC、TG、HDL和FINS均显著升高(P<0.05、0.01)。与小鼠对照组比较,db/db、ob/ob、KK-ay小鼠组FBG、TC、TG、HDL、LDL和FINS均显著升高(P<0.05、0.01)(其中db/db小鼠LDL除外)。组织病理学检查结果显示,与大鼠对照组比较,高脂高糖+四氧嘧啶组与高脂高糖+链脲佐菌素组胰岛萎缩,体积减小,数量减少,分布稀疏,形态极不规则,胰岛细胞空泡样变,数目减少,β细胞坏死凋亡;肝脏可见不同程度的肝细胞空泡变性;ZDF大鼠组胰岛萎缩,体积减小,形状不规则,边界不清,炎细胞浸润,纤维组织增生,岛内β细胞凋亡,形态不清,排列紊乱;轻微至轻度肝细胞空泡变性。与小鼠对照Absract:Objective The biochemical indexes and the histopathological changes of islet and liver in six common type 2 diabetic animal models were compared,providing help for the related experimental research of type 2 diabetes.Method Rats and mice of each 32,divided into eight groups,eight rats in each group,including control group of rats(SD rats),high fat and high glucose+ALX group(SD rats),high fat and high glucose+STZ group(SD rats),ZDF rats,control group of mice(C57 BL mice),db/db mice,ob/ob mice and KK-ay mice.Type 2 diabetes mellitus models were established:rats in high fat and high glucose+ALX group and high fat and high glucose+STZ group were fed with high fat and high glucose diet for six weeks,and following with once ip of 150 mg/kg of ALX and 30 mg/kg of STZ,respectively,ZDF rats were fed with Purina#5008 diet for six weeks;C57 BL,DB/DB and ob/obmice were fed with normal diet and KKay mice were fed with high-fat diet for eight weeks.Fasting blood glucose(FBG),fasting insulin(FINS),TC,TG,HDL,LDL were measured in the anterior abdominal aorta,and the pathomorphological observation of the pancreas and liver was taken.Result The results of body weight measurement showed that:during the experiment,the body weight increased significantly in the control group of rats,high fat and high glucose+ALX group,high fat and high glucose+STZ group,and decreased slowly in the ZDF group;the body weight increased slowly in the control group of mice,db/db mice group,the ob/ob mice group and the KK-ay mice group.The results of blood lipid,blood glucose and fasting insulin showed that:compared with the control group of rats,FBG,TC and TG in high fat and high glucose+ALX group and high fat and high glucose+STZ group were significantly increased(P<0.01),FINS were significantly decreased(P<0.01);FBG,TC,TG,HDL and FINS in ZDF group were significantly increased(P<0.05、0.01).Compared with the control group of mice,the FBG,TC,TG,HDL,LDL and FINS in the db/db mice,the ob/ob mice and the KK-ay mice increased significantly(P<0.05,0.01

关 键 词：大鼠 小鼠 2型糖尿病 胰岛 肝脏 病理 生化 

分 类 号：R965.1[医药卫生—药理学]