2型糖尿病模型小鼠造模时间的选择*

doi:10.12047/j.cjap.5728.2019.034

摘要/Abstract

摘要： 目的: 分析不同时期的2型糖尿病小鼠血生化指标及心肌和肾脏的病理变化情况,为选择2型糖尿病模型小鼠造模时间提供依据。方法: 32只健康雄性ICR小鼠高脂饲料喂养6周后,腹腔注射链脲佐菌素(STZ, 30 mg/kg),连续5 d,制备糖尿病模型。9 d后测空腹血糖(FBG),高于11.1 mmol/L视为糖尿病模型。分别于成模后第4、6、8周处死一组小鼠。另取8只雄性ICR小鼠作为对照组,常规饲料喂养,于糖尿病组小鼠成模后第8周处死。分析小鼠生化及病理情况:①心脏、肾脏脏器系数计算;②血清乳酸脱氢酶(LDH)、肌酸激酶(CK)、肌酐(Cr)和尿素氮(BUN)含量测定;③ HE染色观察心肌和肾脏组织病变的整体情况;Masson染色观察心肌组织纤维化情况;PAS染色观察肾脏组织病理变化。结果: 与对照组小鼠进行比较,第4、6、8周的糖尿病小鼠心脏器系数升高,血清LDH、CK升高,病理组织学见心肌细胞肥大,纤维化;肾脏脏器系数升高,肾功能肌酐(Cr)、尿素氮(BUN)显著升高,病理组织学见肾小球肥大,肾小管基底膜增厚,管腔萎缩。结论: 第6周糖尿病小鼠相关生化病理指标改变相对明显且饲养时间相对较短,故2型糖尿病模型小鼠造模后第6周是进行药物干预和病理、生理、生化等研究的最佳时间。

关键词: 糖尿病模型, 病理, 生理, 糖尿病心肌病, 糖尿病肾病, 小鼠

Abstract: Objective: To analyze the changes of blood biochemical index and the pathological changes of myocardium and kidney in type 2 diabetic mouse at different time points, which can provide the basis for the selection of type 2 diabetic modeling time for later research. Methods: After 6 weeks of feeding with high-fat diet, 24 healthy male ICR mice were injected with streptozocin (STZ, 30 mg/kg) intraperitoneally for 5 days to establish diabetic models. After 9 days, a random blood glucose ≥ 11.1 mmol / L was measured as diabetic mice. 4, 6 and 8 weeks after successfully preparing the diabetic mouse, 8 diabetic mice (a group)would be sacrificed each time. Then the biochemical and pathological conditions were analyzed: ① the indexes of heart and kidney were calculated. ②the serum levels of creatine kinase (CK), lactate dehydrogenase (LDH), creatinine (Cr) and blood urine nitrogen (BUN) were determined. ③ Histopathological changes of myocardium and renal tissues were observed by hematoxylin and eosin (HE) staining. Masson staining was used to observe the fibrosis of myocardium. PAS staining was adopted to observe the pathological changes of renal tissue. In addition, 8 ICR male mice were taken as the control group. Results: At the 4^th, 6^th and 8^th week, cardiac organ coefficient, the values of LDH and CK were all increased compared with the control group. Cardiomyocyte hypertrophy and myocardial fibrosis could be observed. Renal organ coefficient, the values of Cr and BUN were increased. Glomerular hypertrophy, basement membrane thickening and atrophy could be perceived. Conclusion: At the 6^th week, related biochemical and pathological changes in diabetic mice were comparatively obvious and breeding time was relatively short. Thus, 6 weeks after the preparation of the diabetic mice would be the optimal time for type 2 diabetes mellitus modeling, proper for inventions of drugs and other research purposes including pathology, physiology, biochemistry, etc.

Key words: diabetes model, pathology, physiology, diabetic cardiomyopathy, diabetic nephropathy, mice

杨张良, 童海玲, 孙梦蝶, 袁杰, 胡莺, 王旭焘, 齐敏友. 2型糖尿病模型小鼠造模时间的选择^*[J]. 中国应用生理学杂志, 2019, 35(2): 155-159.

YANG Zhang-liang, TONG Hai-ling, SUN Meng-die, YUAN Jie, HU Ying, WANG Xu-tao, QI Min-you. Selection of modeling time for type 2 diabetes mellitus mouse[J]. CJAP, 2019, 35(2): 155-159.

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2型糖尿病模型小鼠造模时间的选择^*

Selection of modeling time for type 2 diabetes mellitus mouse

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