天津医药

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雷帕霉素对糖尿病肾病大鼠的保护作用

冯欣1,李垚2,王雪鹰3   

  1. 1. 辽宁医学院附属第一医院
    2. 辽宁医学院
    3. 锦州市中心医院
  • 收稿日期:2010-06-18 修回日期:2011-01-25 出版日期:2011-06-15 发布日期:2011-06-15
  • 通讯作者: 冯欣

Protective Effect of Rapamycin On The Renal of Diabetic Rats

  • Received:2010-06-18 Revised:2011-01-25 Published:2011-06-15 Online:2011-06-15

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摘要： 目的：本实验主要研究雷帕霉素（rapamycin，RAPA）对糖尿病大鼠肾脏的保护作用及可能机制。方法：将36只大鼠随机分为3组：正常对照组：12只；糖尿病组：12只；糖尿病雷帕霉素治疗组：12只。链脲佐菌素腹腔注射制作糖尿病大鼠模型。检测大鼠生化指标改变，做组织学检查，观察肾组织病理改变，用westhern blot方法检测肾组织中细胞增殖核抗原（PCNA）和Ⅳ型胶原（COL-Ⅳ）蛋白的水平。结果：与对照组相比，糖尿病组大鼠Glu、Scr、BUN、和UPro均显著上升，大鼠肾脏明显肥大，肾小球肥大，毛细血管基底膜厚度显著增加，肾皮质PCNA及COL-Ⅳ的蛋白表达显著上调。雷帕霉素治疗后，上述指标除血糖外均部分被抑制。结论：雷帕霉素能够减轻糖尿病大鼠肾脏的肥大，抑制系膜外基质聚集，下调PCNA及COL-Ⅳ的表达，延缓糖尿病肾病的进展。

关键词: 雷帕霉素, 细胞增殖核抗原, Ⅳ型胶原

Abstract: Objective: To evaluate protective effects and possible mechanism of rapamycin (RAPA) on the renal of diabetic rat. Methods: 36 rats were randomly divided into 3 groups: control group: 12 rats; diabetic group: 12 rats; RAPA treatment group: 12 rats. Diabetic model rats were made by injecting streptozotocin into abdomen. Biochemical changes and histological changes were obsvered. The expression of proliferating cell nuclear antigen (PCNA) and Ⅳ collagen (COL-Ⅳ) were detected by westhern blot. Results: Compared with the control group, the level of Glu, Scr, BUN, and UPro were significantly increased in diabetes group. Kidney hypertrophy, glomerular hypertrophy, basement membrane thickness were significantly increased renal cortex and COL-Ⅳ、PCNA protein expression was up. After RAPA intervention, the above parameters, except blood glucose were partially inhibited. Conclusion: RAPA can reduce kidney hypertrophy in diabetic rats, inhibition of mesangial extracellular matrix accumulation, reduced the expression of COL-Ⅳ and PCNA, delay progression of diabetic nephropathy.

Key words: Rapamycin, proliferating cell nuclear antigen, Ⅳ collagen