摘要
目的构建单侧肾切除联合尾静脉注射阿霉素(ADR)法造成的SD大鼠慢性肾衰竭(CRF)模型,经尾静脉注射人脐带间充质干细胞(MSC),观察外源性促红细胞生成素(EPO)对移植MSC修复CRF效应的影响。方法将SD大鼠分为5组,每组12只,分为正常对照组,CRF组,MSC+CRF组,EPO+CRF组,EPO+MSC+CRF组,建模后第4、8、12周各组分别随机取4只大鼠腹腔静脉血,检测血清尿素氮(BUN)、肌酐(Screa),用TBA法检测氧化应激指标丙二醛(MDA)、WST法检测超氧化物歧化酶(SOD)和血管生成素(Ang-1)的含量;第12周时观察肾组织的病理变化。结果血清BUN和Screa与CRF组比较,MSC+CRF组、EPO+CRF组、EPO+MSC+CRF组均下降,EPO+MSC+CRF组下降最明显,MSC+CRF组次之(P<0.05)。血清MAD建模后CRF组4周开始升高,8周和12周达到高峰,与CRF组相比较,EPO、MSC、EPO+MSC干预均可以降低MAD,EPO+MSC+CRF组的MAD下降最明显(P<0.05)。血清SOD建模后CRF组4周开始下降,8周和12周达到最低,与CRF组相比,EPO、MSC、EPO+MSC干预均可以升高SOD和Ang-1,EPO+MSC+CRF组升高最明显。肾脏病理结果显示与CRF组相比,EPO+CRF组和MSC+CRF组大鼠肾小管损伤及肾间质纤维化均有所改善,尤其是EPO+MSC+CRF组大鼠,肾小球的病理改变相对较轻,个别肾小管可见上皮细胞再生。结论EPO干预MSC移植治疗可改善CRF大鼠的肾功能和氧化应激,可加强MSC修复损伤的肾组织,EPO和MSC共同干预CRF大鼠优于单纯使用MSC或EPO,为治疗CRF提供一种新手段。
Objective To construct a model of chronic renal failure(CRF) in SD rats caused by unilateral renal resection combined with repeated caudal intravenous administration of doxorubicin(ADR).The effects of exogenous erythropoietin(EPO)on the repair of CRF by Umbilical Cord mesenchymal stem cells(MSC)grafted via tail vein were observed.Methods SD rats were divided into 5 groups,12 for each group,and divided into normal control group,CRF group,MSC+CRF group,EPO+CRF group,EPO+MSC+CRF group,At week 4,8 and 12,four rats were randomly selected from each group to test the BUN,Screa,MDA,SOD and Ang-1.Results Compared with CRF group,blood serum BUN and Screa decreased in MSC+CRF group,EPO+CRF group,EPO+MSC+CRF group,and EPO+MSC+CRF group.EPO+MSC+CRF group showed the most obvious decrease,followed by MSC+CRF group.Compared with the CRF group,the effect of EPO,MSC,EPO+MSC intervention on MAD decrease was most obvious in the EPO+MSC+CRF group.Serum SOD began to decline at 4W in CRF group,and 8W and 12W reached the lowest level.Compared with the CRF group,EPO,MSC,EPO+MSC intervention all increased SOD,while EPO+MSC+CRF group increased SOD and Ang-1 most significantly.Compared with the CRF group,renal tubular injury and renal interstitial fibrosis were improved in the EPO+CRF group and the MSC+CRF group,especially in the EPO+MSC+CRF group,the pathological changes of renal glomeruli were relatively light,and epithelial cell regeneration was observed in some renal tubules.Conclusion EPO intervention combined with MSC transplantation can improve renal function and oxidative stress in CRF rats and strengthen the repair of damaged renal tissue by MSC.EPO intervention combined with MSC transplantation is superior to the use of MSC or EPO alone,providing a new method for the treatment of CRF.
作者
蒋红樱
张曦
张乐航
曾怡
彭文芳
白彝华
JIANG Hong-ying;ZHANG Xi;ZHANG Yue-hang;ZENG Yi;PENG Wen-fang;BAI Yi-hua(Dept.of Nephrology,The 2nd Affiliated Hospital of Kunming Medical University,Kunming Yunnan 650101;Dept.of Nephrology,Gan Mei Hospital Affiliated to Kunming Medical University,Kunming Yunnan 650224;Dept.of Nephrology,The Fourth People's Hospital of Kunming,Kunming Yunnan 650302,China)
出处
《昆明医科大学学报》
CAS
2019年第7期30-35,共6页
Journal of Kunming Medical University
基金
云南省科技厅-昆明医科大学应用基础研究联合专项基金资助项目[2017FE468(-202),2017FE468(-157)]
云南省教育厅科学研究基金资助项目(2015Z085)
关键词
红细胞生成素
人脐带间充质干细胞
慢性肾衰竭
丙二醛
超氧化物歧化酶
Erythropoietin
Umbilical cord mesenchymal stem cells
Chronic renal failure
Malondialdehyde
Superoxide dismutase
