| 王阜蕾,张妍春,陈媛媛,刘 祁,周 健.STZ诱导的糖尿病模型小鼠肾脏的上皮-间质转分化研究[J].,2017,17(18):3413-3418 |
| STZ诱导的糖尿病模型小鼠肾脏的上皮-间质转分化研究 |
| A Study on the Epithelial-mesenchymal Transition in the Kidney of Diabetic Mice Model Induced by STZ |
| 投稿时间：2017-03-12 修订日期：2017-03-31 |
| DOI：10.13241/j.cnki.pmb.2017.18.003 |
| 中文关键词: 链脲佐菌素 上皮-间质转分化 肾脏 糖尿病 |
| 英文关键词: Streptozotocin Epithelial-mesenchymal transition Kidney Diabetes mellitus |
| 基金项目:国家自然科学基金项目(81370998)；陕西省科技统筹创新工程项目(2012KTCQ03-03) |
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| 中文摘要: |
| 摘要 目的：探讨STZ诱导的糖尿病小鼠肾脏发生上皮-间质转分化(EMT)的情况。方法：将80只C57BL小鼠随机分为正常对照组(NC组)和糖尿病组(DM组)，每组40只。DM组小鼠用1%STZ(streptozotocin，链脲佐菌素)溶液按60mg/kg 体质量的剂量进行腹腔注射，每天1次，连续6天。NC组小鼠平行腹腔注射同等体积0.1mol/L的柠檬酸钠缓冲液。再将成模小鼠随机分为A、B批次，A批次用于动态观察生存率、小鼠体质量及随机血糖的监测；B批次用于在造模后第4、8、12周末观察肾组织的病理变化，并用Western blot、免疫荧光染色的方法观察肾组织中EMT标志蛋白α-SMA和E-cadherin的表达。结果：STZ诱导的糖尿病模型小鼠出现糖尿病典型症状如多饮、多尿等，血糖持续在高水平状态，体质量增长缓慢。在造模后12周末，DM组小鼠较NC组小鼠累积生存率显著降低，两组比较差异具有统计学意义(P<0.001)。在造模后的第8周末，DM组小鼠肾脏出现明显的病理改变，到第12周末时，绝大部分肾小管上皮细胞被梭形的肌成纤维细胞取代，肾小球空泡，基底膜增厚。造模后的第4、8、12周末时，DM 组小鼠E-cadherin表达量均显著低于NC组小鼠(P=0.004，0.026，0.004)；而在第8和12周末时，DM组α-SMA表达量显著升高(P=0.009，0.015)。在第12周末，肾组织冰冻切片E-cadherin和α-SMA、免疫荧光染色结果与上述结果一致。结论：STZ诱导的糖尿病模型小鼠有较典型的糖尿病临床改变，且肾组织发生了EMT。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the incidence of epithelial-mesenchymal transition(EMT) in the kidney of streptozotocin induced diabetic mice. Methods: Eighty C57BL mice were randomly divided into normal control group (NC group) and diabetic group (DM group). Forty mice in DM group were injected intraperitoneally with 1% STZ (streptozotocin) at the dose of 60 mg/kg body weight once a day, for six consecutive days. The other forty mice in NC mice were injected with 0.1 mol/L sodium citrate buffer at the same time and at the same volume with the mouse in DM group. Then the mice in two groups were randomly divided into batch A and batch B. Mice in batch A were used for monitoring the survival rate, body weight and random blood glucose dynamically. Mice in batch B were applied for histopathological changes study, Western blot assay and immunofluorescence staining to observe the changes of proteins α-SMA and E-cadherin in renal tissues at the ends of the 4th, 8th, and 12th week after the DM model was established. Results: Mice in DM group showed typical symptoms of diabetes, such as polydipsia and polyuria, high levels of blood glucose, slow growth of body weight, comparing with the mice in NC group. By the twelve-week observation, the survival rate of mice in DM group was significantly lower than that in NC group (P<0.001). At the end of the 8th week, obvious histopathological changes were showed in the kidney of DM group. By the end of the 12th week, further damages increased, for instance, the vast majority of renal tubular epithelial cells were changed into spindle shaped fibroblasts, vacuoles were showed in glomerulus, and glomerular basement membrane were thicken. Western blot detection showed that in DM group E-cadherin expressions were significantly lower than that in NC group (P=0.004, 0.026, 0.004) at the ends of the 4th, 8th, and 12th week, while α-SMA expressions increased significantly (P=0.009, 0.015) at the ends of the 8th and 12th week. Immunofluorescence staining showed that the expressions of E-cadherin and α-SMA in the frozen sections of kidney tissues in DM group at the 12th week were consistent with the results of those in Western blot assay. Conclusion: STZ induced diabetic mice had typical clinical changes of diabetes mellitus, including EMT in renal tissues. |
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