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秋水仙碱对肾间质纤维化大鼠细胞表型改变的影响

Effects of colchicine on cell phenotypic change in rats with unilateral ureteral obstruction

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【作者】 黄文彦孙骅潘晓勤费莉郭梅张爱华吴元俊黄松明陈荣华姜新猷

【Author】 HUANG Wenyan 1 , SUN Hua 1 , PAN Xiaoqin 2 , FEI Li 2 , GUO Mei 2 , ZHANG Aihua 2 , WU Yuanjun 2 , HUANG Songming 2 , CHEN Ronghua 2 , JIANG Xinyou 1 1Department of pediatrics, the second affiliated hospital of Nanjing Medical University; The center of pediatric nephrology, Nanjing Medical University Nanjing 210011 2The center of pediatric nephrology, Nanjing Medical University

【机构】 南京医科大学第二附属医院儿科南京医科大学小儿肾脏病研究中心南京医科大学第二附属医院儿科 南京医科大学小儿肾脏病研究中心南京210011复旦大学儿科医院上海300032南京医科大学小儿肾脏病研究中心210011

【摘要】 目的 :明确细胞表型改变在肾间质纤维化中的作用和意义 ,以及秋水仙碱对细胞表型改变的影响。  方法 :通过经典的单侧输尿管梗阻 (UUO)肾间质纤维化模型 ,利用RT PCR和免疫组化法分别观察模型组、秋水仙碱治疗组实验第 3天、第 7天、第 14天和第 2 1天肾组织α 平滑肌肌动蛋白 (α SMA)mRNA和蛋白表达、分布规律。  结果 :①UUO后肾皮质α SMAmRNA表达于实验第 3天、第 7天、第 14天、第 2 1天分别上调 2 1倍 (2 5 1± 3 6vs11 9± 31 7)、3 9倍 (46 4± 3 0vs 12 0± 1 8)、4 4倍 (5 3 1± 2 9vs 12 1± 2 1)和 3 7倍 (47 5± 3 1vs 12 8± 1 5 ) ;α SMA肾间质阳性表达指数进行性增加 ,分别为 :19 9± 2 6、32 6± 3 1、5 4 8± 4 4、6 3 5± 4 6 (模型组组间比较 ,F =113 3,P <0 0 0 1)。秋水仙碱治疗组在整个实验过程中肾皮质仅微弱表达α SMA ,其mRNA和蛋白表达水平均极显著低于同期模型组 (P <0 0 0 1)。②正常肾组织仅在肾间质血管壁见α SMA表达 ,肾小管上皮细胞、间质以及肾小球均未见表达。第 7天开始肾小管上皮细胞见α SMA明显表达并进行性加重。模型组皮质肾小管α SMA阳性细胞数第 7、14、2 1天分别为 :(12 5± 2 1)个 /HP、(5 8 9± 4 6 )个 /HP、(6 7 3± 4 5 )?

【Abstract】 Objective: To investigate the role of cell phenotypic change on renal interstitial fibrosis (RIF), and the effects of colchicine on cell phenotypic change. Methodology: Expression of α SMA of renal tissues from both unilateral ureteral obstruction (UUO) group and colchicine-treated group were studied using RT PCR and immunohistochemistry. Results: ① The results of RT PCR showed, in UUO group, expression of α SMA mRNA was up regulated 2.11, 3.86, 4.39 and 3.70 folds at 3, 7, 14, and 21st day, respectively. Immunohistochemistry showed that positive interstitial area of α SMA was enhanced progressively. At 3, 7, 14, and 21st day, the expression index were 19.87±2.58, 32.63±3.07, 54.77±4.43, and 63.52±4.57 respectively (UUO group, within group, F =113.29, P < 0.001). While in colchicine treated group, the levels of both mRNA and protein of α SMA were significantly reduced ( P < 0.001). ② Expression of α SMA protein manifested in tubular epithelial cells at 7th day, and that kept increasing afterward. At 7, 14, and 21st day after UUO, the positive numbers of tubular epithelial cells which expression of α SMA protein were(12.48±2.08) cells/HP,(58.87±4.56) cells/HP,and (67.31± 4.51) cells/HP respectively. The colchicine could significantly reduce the numbers of cells which expression of α SMA protein compare with that of UUO group ( P <0.01). Conclusion: ① The extensive phenotypic change of renal cells was found in RIF of UUO group, in which renal tubular epithelial trans differentiated into myofibroblast and contribute to the progression of RIF. ② Colchicine had strikingly inhibitory effects on cell phenotypic change.

【基金】 江苏省卫生厅重点资助项目(NO :H990 6);江苏省教委资助项目(NO :99KDJ3 2 0 0 11)
  • 【文献出处】 肾脏病与透析肾移植杂志 ,Chinese Journal of Nephrology, Dialysis & Transplantation , 编辑部邮箱 ,2003年05期
  • 【分类号】R965
  • 【被引频次】7
  • 【下载频次】120
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