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

Transplantation of marrow mesenchymal stem cells through renal artery in repair of acute tubular necrosis in nude mice

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。

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 ceils.