骨髓间充质干细胞肾动脉注射移植修复裸鼠急性肾小管坏死
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上海市黄浦区卫生事业发展奖励基金(HWY-2004128).


Transplantation of marrow mesenchymal stem cells through renal artery in repair of acute tubular necrosis in nude mice
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Supported by the Grants from the Huangpu Health Development Program of Shanghai(HWY-04128).

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    摘要:

    目的:探讨骨髓间充质干细胞(MSCs)移植对裸鼠急性肾小管坏死(ATN)的修复作用,为MSCs移植治疗ATN提供实验依据。方法:5周龄裸鼠随机分为健康对照组、ATN模型组、MSCs移植治疗组。ATN模型采用50%甘油肌内注射诱导,MSCs移植采用经肾动脉注射途径向肾脏内移植增强型绿色荧光蛋白(EGFP)标记的MSCs。实验期间观察饮食、活动等变化,检测血肌酐(Scr)水平,H-E染色观察肾组织病理学变化,荧光显微镜观察EGFP标记的阳性细胞在裸鼠肾脏的分布及数量。结果:ATN模型组裸鼠肾脏肾小管上皮细胞变性、局部坏死,病变于肾皮质或皮髓交界处明显,而肾小球未见明显异常。MSCs移植治疗组的肾小管上皮细胞无混浊肿胀和细胞核固缩溶解,间质无明显的充血和水肿。MSCs细胞移植后第14天的受体鼠肾小管中EGFP阳性细胞明显增多。结论:肾动脉注射途径移植的MSCs能定位于肾小管上皮,可促进ATN中损伤的肾小管上皮细胞的修复。

    Abstract:

    Objective:To investigate whether transplantation of mesenchymal stem cells(MSCs) through renal arteries can protect kidney from acute tubular necrosis(ATN),so as to lay a foundation for MSC transplantation in treatment of ATN.Methods: Five-week-old nude mice were randomly divided into three groups:normal control group(n=10),acute tubular necrosis(ATN) model group without(n=10) and with MSCs treatment group(n=11).ATN nude mice were induced with 50% glycerin.MSCs labeled with enhanced green fluorescent proteins(EGFP) were injected into kidney through renal arteries.Serum creatinine was determined in all groups and pathological changes of renal tissues were detected using H-E staining.The amount and distribution of the EGFP-marked MSCs in renal tissues were determined with fluorescence microscope.Results: Degeneration and exfoliation of renal tubular epithelial cells,and even renal tubular tamponade with cast-off cells were observed in the ATN group; these pathological changes were mainly located at renal cortex and juncture of renal cortex and medulla.The damages were greatly alleviated in the ATN+MSCs transplantation group,with no swelling of epithelial cells,nuclear condensation or edema.Fourteen days after MSCs transplantation,EGFP positive cells were increased in renal tubules of recipient mice.Conclusion: The MSCs transplantation via renal artery can locate in renal tubular epithelium,and promote the repair of injured renal tubular epithelial cells.

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  • 收稿日期:2008-10-20
  • 最后修改日期:2009-04-09
  • 录用日期:2009-05-12
  • 在线发布日期: 2009-06-18
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