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依普利酮对环孢素A急性肾损伤小管上皮细胞坏死及再生的作用

Effect of eplerenone on necrosis and regeneration of tubular epithelial cells in acute cyclosporine nephrotoxicity

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【作者】 许庆友贾晓明丁英钧王筝王香婷穆胜宇史亚男王红下泽达雄藤田敏郎

【Author】 XU Qing-you~1,JIA Xiao-ming~2,DING Ying-jun~1,WANG Zheng~1,WANG Xiang-ting~1,MU Sheng-yu~3,SHI Ya-nan~3,WANG Hong~3,SHIMOSAWA Tatsuo~3,FUJITA Toshiro~3 (1.College of Integration of Chinese and Western Medicine,Hebei Medical University,Shijiazhuang 050091,China;2.Institute of Traditional Chinese Medicine,Hebei Medical University,Shijiazhuang 050031,China;3.Dept of Endocrinology and Nephrology,Faculty of Medicine,The University of Tokyo,Tokyo Japan)

【机构】 河北医科大学中西医结合学院内科教研室河北医科大学中医药研究院日本东京大学医学部肾脏内分泌科

【摘要】 目的观察盐皮质激素受体阻断剂依普利酮保护环孢素A肾病小管上皮细胞的作用。方法经口灌服环孢素A(100 mg.kg-1.d-1),诱导小鼠急性肾脏损伤,给予依普利酮100 mg.kg-1.d-1治疗,d 5将5-溴脱氧尿嘧啶核苷(40mg.kg-1.d-1)经微型渗透泵皮下注入,10 d后摘取肾脏,HE、PAS检测肾脏病理改变,免疫组化检测5-溴脱氧尿嘧啶核苷阳性细胞标记再生细胞。结果肾脏病理显示环孢素A组小管上皮细胞坏死、小球包氏囊增厚、间质纤维成分沉积,凋亡细胞增多,免疫组化显示再生细胞数量减少,依普利酮治疗组上皮细胞坏死减轻,间质纤维沉积减少,再生细胞明显增多。结论依普利酮可以通过对醛固酮受体的阻断减轻环孢素A诱导的急性肾脏损伤。

【Abstract】 Aim To investigate the effect of minerallocorticoid receptor blockade eplerenone on necrosis and regeneration in tubular epithelial cells in acute cyclosporine nephrotoxicity.Methods Acute cyclosporine nephrotoxicity in mice was induced with cyclosporine A orally with 100 mg·kg~1·d~-1 and treated with Eplerenone 100 mg·kg~-1·d~-1.The 5Bromodeoxyuridine(BrdU)in mini-osmotic pump hypodermic was injected on the fifth day and the kidneys were harvested on the 10~th day.Renal pathological changes were detected with HE and PAS staining.Regenerative cells were marked with BrdU in immunohistochemistry.Results Cyclosporine induced the cell necrosis,thickened Bowmans,over deposited extracellular matrix,increased cell apoptosis and reduced regenerative cells.Cell necrosis and over-production of extracellular matrix were inhibited in Eplerenone treated group,and the regenerative cells increased in the kidneys.Conclusion Eplerenone plays a role in inhibing the acute cyclosporine nephrotoxicity by blocking aldosterone receptor.

【基金】 河北省优秀专家出国培训资助项目(2008年)
  • 【文献出处】 中国药理学通报 ,Chinese Pharmacological Bulletin , 编辑部邮箱 ,2010年07期
  • 【分类号】R965
  • 【被引频次】9
  • 【下载频次】232
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