同种异体骨髓间充质干细胞对肾小管周毛细血管丛修复影响的研究

作者	单位
邹杰	中国医科大学第一附属医院肾脏内科
冯江敏	河南省中医药研究院 (沈阳110011)
李维	河南省中医药研究院 (沈阳110011)
郭伟	河南省中医药研究院 (沈阳110011)
王力宁	河南省中医药研究院 (沈阳110011)

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中文摘要:

目的探讨同种异体Wistar大鼠骨髓间充质干细胞(MSCs)是否具修复肾小管周毛细血管丛(PTC)潜能,同时观察其对肾小管-间质低氧状态的改善。方法从骨髓中提纯单核细胞,体外扩增、鉴定为MSCs。将30只雌性大鼠随机分为非移植组、MSCs移植组及正常对照组。非移植组和MSCs移植组经关木通水煎剂灌胃12周,制成慢性马兜铃酸肾病(CAAN)大鼠模型。第12周,MSCs移植组经尾静脉输入1mL MSCs悬液;非移植组和正常对照组经尾静脉输入1mL生理盐水。第16周留取血、尿及肾组织标本。肾组织连续切片,检测Y染色体和CD34双阳性细胞的分布,并作病理、免疫组织化学、Western blotting、RT-PCR等检查。结果MSCs移植组肾组织中可见Y染色体和CD34双阳性细胞。第16周,非移植组与MSCs移植组结果:PTC密度分别为(5.26±0.78)/0.13mm2、(26.47±1.56)/0.13mm2(P<0.01);低氧诱导因子1α(hypoxia inducible factor-1α,HIF-1α,IOD值)分别为(6.74±0.67)×103、(25.27±1.46)×103(P<0.01);MSCs移植组较非移植组CD34显著增强(P<0.01)。结论同种异体MSCs可向肾小管周毛细血管丛内皮细胞分化修复PTC,从而改善肾小管-间质低氧状态。

英文摘要:

Objective To investigate the potential effect of homologous bone marrow mesenchymal stem cells(MSCs)on repairing peri-tubular capillary cluster(PTCC),and on improving renal tubular and mesenchymal hypoxia condition.Methods Monocyte was purified from bone marrow,amplified and identified as MSCs in vitro.Thirty female Wistar rats were randomly divided into 3 groups,the normal control group(Group A),MSCs transplanted group(Group B)and un-transplanted group(Group C).Rats in Group A was administered with drinking water by gastrogavage for 12 weeks,while those in Group B and C were administered with Aristolochia Decoction for 12 weeks to establish chronic aristolochic acid nephropathy(CAAN)model.At the end of the 12th week,1 ml of MSCs was injected through caudal vein to the rats in Group B,while to those in Group A and C normal saline was injected instead.Blood,urine and kidney tissue of rats were collected at the end of the 16th week for examination,and their kidney tissue were made into serial section for determining the distribution of Y chromosome and CD34 double positive cells,and the pathological,immunohistochemical changes were observed using Western blotting and RT-PCR,etc.Results Y chromosome and CD34 double positive cells could be seen in MSCs transplanted renal tissue in group B.At the end of the 16th week,the PTCC density in Group C and B was(26.47±1.56)/0.13mm2 and(5.26±0.78)/0.13mm2 respectively,and the IOD value of hypoxia inducible factor-1α(HIF-1α)in them was(6.74±0.67)×103 and(25.27±1.46)×103 respectively,all showing significant difference between the two groups(P<0.01).The content of CD34 was higher in Group B than that in Group C(P<0.01).Conclusion Homologous MSCs can enhance the vascular endothelial cells differentiation to repair the PTCC,thus to improve the renal tubular and mesenchymal hypoxia status.

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