国际病理科学与临床杂志 2010, 30(1) 33- DOI:   10.3969/j.issn.16732588.2010.  ISSN: 1673-2588 CN: 43-1458/R
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本文关键词相关文章
糖尿病肾病
糖尿病
吡格列酮
单核细胞趋化蛋白1
大鼠
本文作者相关文章
PubMed
吡格列酮对2型糖尿病大鼠肾脏及单核细胞 趋化蛋白1表达的影响
章容， 李素梅， 叶山东， 翟斐， 张丽
安徽医科大学附属省立医院内分泌科， 合肥 230041
摘要： 目的：观察吡格列酮对2型糖尿病(Type 2 diabetes mellitus，T2DM)大鼠血、尿单核细胞趋化蛋白1（monocyte chemoattractant protein1，MCP1）表达及肾脏组织结构和功能的影响。方法：正常对照组(NC组)喂以常规饲料；采用高糖高脂膳食、小剂量链脲佐菌素（streptozotocin，STZ）注射的方法建立2型糖尿病大鼠模型，将成模的大鼠随机分为糖尿病（DM组）和吡格列酮（PIO组），后用吡格列酮对PIO组大鼠进行干预治疗。8周后检测血糖水平、尿生化结果、肾脏组织病理的改变情况，同时检测尿MCP1指标的变化。结果：与NC组比较，DM组和PIO组第8周空腹血糖及糖化血红蛋白水平均明显升高，但DM组、PIO组间差异无统计学意义（P＜0.05）；第8周DM组、PIO组尿白蛋白/尿肌酐(urinary albumin／creatinine ratio，ACR)、尿视黄醇结合蛋白(urinary retinol bindingprotein，URBP)、尿MCP1(urinary monocyte chemoattractant protein1，UMCP1)和肾脏肥大指数均高于NC组，PIO组4项指标较DM组明显降低，且UMCP1与ACR，URBP及肾脏肥大指数呈正相关；病理显示PIO组大鼠肾小球病变程度均较DM组明显减轻，MCP1表达减少。结论：吡格列酮对2型糖尿病大鼠肾脏有明显的保护作用，这种保护作用是独立于降糖作用之外的。其机制可能与其抑制肾组织MCP1表达及其排泄有关。
关键词： 糖尿病肾病   糖尿病   吡格列酮   单核细胞趋化蛋白1   大鼠  
Effect of pioglitazone on renal and MCPl expression in Type 2 diabetic rats
ZHANG Rong, LI Sumei, YE Shandong, ZAI Fei, ZAHNG Li
Department of Endocrinology，Anhui Provincial Hospital Affiliated Anhui Medical University，Hefei 230041, China
Abstract: Objective To observe the effect of pioglitazone on monocyte chemoattractant protein1(MCP1) level in the serum and urine, on MCP1 expression in the kedney, and on renal constitution and function in Type 2 diabetic (T2DM) rats. MethodsThe normal control group (NC group) fed with normal diet. The model of T2DM rat was established by fed with highsucrosehighfat diet and injected low dose of streptozotocin （STZ）. For the pioglitazone (PIO) group, the T2DM rats received PIO intervention. After 8 weeks, blood glucose levels, urine and biochemical regular index, and renal pathological changes were examined. The urinary MCP1 index was also detected.ResultsCompared with the NC group, fasting blood glucose and glycated hemoglobin were significantly increased in the diabetes group (DM group) There was no significant difference between the DM group and the PIO group. The urinary albumin / urinary creatine (ACR), urinary retinolbinding protein (URBP), urinary MCP1 (UMCP1), and renal hypertrophy index in the DM and the PIO group were higher than those in the NC group. Whereas the four abovementioned indicators were significantly lower in the PIO Group compared with the DM group. The UMCP1 positively correlated with ACR, URBP, and kidney hypertrophy index. Pathological results showed that the extent of glomerular lesions in the PIO group was significantly reduced and MCP1 expression was decreased, compared with that in the DM group.Conclusion Pioglitazone has protective effect on the kidney in Type 2 diabetic rat, which is independent on the hypoglycemic effect. It may be related to the inhibitory effect on MCP1 expression and excretion.
Keywords: diabetic nephropathy；diabetes mellitus；pioglitazone；monocyte chemoattractant protein1；rats  
收稿日期 2009-09-05 修回日期 2009-12-26 网络版发布日期  
DOI: 10.3969/j.issn.16732588.2010.
基金项目:

通讯作者: 李素梅
作者简介:
作者Email: lisumei@medmail.com.cn
参考文献：
［1］Holdsworth SR, Kitching AR, Tipping PG. Chemokine as therapeutic targets for renal diseases［J］. Curr Opin Nephrol Hypertens,2000,9(5):505511. ［2］Agarwal R. Antiinflammatory effects of shortterm pioglitazone therapy in men with advanced diabetic nephropathy［J］.Am J Physiol,2006，290(3):F600F605. ［3］Pistrosch F, Herbing K, Kindel B,et al. Rosiglitazone improves glomerular hyperfiltration, renal endothelial dysfunction, and microalbuminura of incipient diabetic nephropathy in patients［J］.Diabetes,2005,54(7):22062211. ［4］Katavetin P,EiamOng S,Suwanwalaikorn S. Pioglitazone reduces urinary protein and urinary transforming growth factorbeta excretion in patients with Type 2 diabetes and overt nephropathy［J］.J Med Assoc Thai,2006,89(2):170177. ［5］Ohga S, Shikata K, Yozai K,et al. Thiazolidinedione ameliorates renal injury in experimental diabetic rats through antiinflammatory effects mediated by inhibition of NFkappa B activation［J］.Am J Physiol Renal, 2007, 292(4): F1141F1150. ［6］Wada T, Furuichi K, Sakai N, et al. Upregulation of monocyte chemoattractant protein1 in tubulointerstitial lesions of human diabetic nephropathy［J］.Kidney Int, 2000，58(4):14921499. ［7］Martin T，Cardarelli PM，Parrv GC，et al. Cytokine induction of monocyte chemoattractant protein1 gene expression in human endothelial cells depends on the cooperative action of NFkappa B and Ap1［J］.Eur J Immunol, 1997，27(5):10911097.
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