间充质干细胞修复大鼠缺血再灌注肾损伤中SDF-1/CXCR4轴的调控机制研究  

Study on Regulation Mechanism of SDF-1/CXCR4 Axis in Mesenchymal Stem Cells for Repairing Ischemia Reperfusion Injured Kidney in Rats

作　　者：司晓芸[1] 徐申 毕晓红[1] 吴小燕[1] SI Xiaoyun;XU Shen;BI Xiaohong;WU Xiaoyan(Department of Nephrology,Zhongnan Hospital of Wuhan University,Wuhan Hubei 430071,China)

机构地区：[1]武汉大学中南医院肾内科,湖北武汉430071

出　　处：《华南国防医学杂志》2018年第7期435-439,445,共6页Military Medical Journal of South China

基　　金：湖北省自然科学基金资助项目(2009CDB428;2015CFB407)

摘　　要：目的探讨骨髓间充质干细胞(bone marrow mesenchymal stem cells,BMSCs)移植修复大鼠肾缺血再灌注损伤(ischemia reperfusion injury,IRI)过程中转化生长因子β1(transforming growth factor-β1,TGF-β1)对基质细胞衍生因子1(stromal cells derived factor-1,SDF-1)/CXC趋化因子受体4(CXC chemokine receptor 4,CXCR4)轴的调控作用。方法建立大鼠缺血再灌注肾损伤模型,动物分为5组:对照组、IRI组、BMSCs组、TGF-β1中和抗体组、CXCR4中和抗体组(n均为8)。HE染色观察肾组织形态学改变;Western blot法检测肾组织TGF-β1、SDF-1α和CXCR4蛋白水平;免疫荧光组织化学法检测肾组织CXCR4蛋白表达。结果 IRI大鼠肾皮质肾小管结构破坏、消失、炎性细胞浸润,BMSCs移植能够改善损伤的肾小管,但修复作用可被TGF-β1抗体和CXCR4抗体所抑制。与对照组比较,IRI组、BMSCs组、TGF-β1中和抗体组与CXCR4中和抗体组肾组织TGF-β1蛋白表达明显上调,分别进行组间比较差异具有统计学意义(t分别为-15.508,-18.487,5.749,19.976,P<0.01);与BMSCs组比较,TGF-β1中和抗体组肾组织中TGF-β1蛋白表达水平明显降低,组间比较差异有统计学意义(t=16.380,P<0.01),但CXCR4中和抗体组、IRI组TGF-β1蛋白表达水平变化不大,组间比较差异无统计学意义(P>0.05)。与对照组比较,IRI组、BMSCs组、TGF-β1中和抗体组及CXCR4中和抗体组SDF-1α蛋白表达水平均明显升高,分别进行组间比较差异具有统计学意义(t分别为-15.073,-15.749,-18.934,-19.077,P<0.01),但升高表达的4组间比较差异无统计学意义(F=2.83,P>0.05)。与对照组比较,IRI组、BMSCs组、TGF-β1中和抗体组、CXCR4中和抗体组CXCR4蛋白表达水平明显上调,分别进行组间比较差异具有统计学意义(t分别为-11.205,-20.960,11.925,-9.212,P<0.01);与BMSCs组比较,IRI组、TGF-β1中和抗体组及CXCR4中和抗体组肾组织CXCR4蛋白表达水平均明显下调,分别进行组间比较差异具有统计学意义(t�Objective To explore the regulation mechanism of stromal cells derived factor-1（ SDF-1）/CXC chemokine receptor 4（ CXCR4） axis in bone marrow mesenchymal stem cells（ BMSCs） for repairing ischemia reperfusion injured（ IRI） kidney in rats. M ethods Rat models with IRI were established,and all rats were divided into 5 groups： control group,IRI group,BMSCs group,TGF-β1 neutralize antibody group and CXCR4 neutralize antibody group（ n = 8）. The morphological changes of renal tissues were observed by HE staining,renal TGF-β1,SDF-1 α and CXCR4 protein levels were measured by Western blot,and renal CXCR4 protein expression was detected by immunofluorescence histochemistry. Results The structures of renal tubules of IRI rats were destroyed,disappeared,and inflammatory cells infiltrated. BMSCs transplantation could improve the damaged renal tubules,but the improvement could be inhibited by TGF-β1 antibody and CXCR4 antibody. Compared with the control group,TGF-β1 protein expression levels were significantly increased in IRI group,BMSCs group,TGF-β1 neutralize antibody group and CXCR4 neutralize antibody group（ t =-1 5. 5 0 8,-1 8. 4 8 7,5. 7 4 9,1 9. 9 7 6,respectively,P〈0. 0 1）. Compared with BMSCs group,the TGF-β1 protein expression levels obviously decreased in TGF-β1 neutralize antibody group（ t = 16. 38,P〈0. 01）,but no differences were found in chages of TGF-β1 protein expression levels between IRI group and CXCR4 neutralize antibody group（ P〈0. 0 5）. Compared with control group,SDF-1 α protein expression levels were increased in IRI group,BMSCs group,TGF-β1 antibody group and CXCR4 antibody group（ t =-1 5. 0 7 3,-1 5. 7 4 9,-1 8. 9 3 4,-1 9. 0 7 7,respectively,P〈0. 0 1）,but there was no significantly difference with higher expression among 4 groups（ F = 2. 8 3,P〈0. 0 5）. Compared with control group the CXCR4 protein expression levels were obviously up-regulated in IRI group,BMSCs group,TGF-β1 neutralize antibody group,CXCR4 neutralize antibody group（ t =

关 键 词：骨髓间充质干细胞 缺血再灌注 转化生长因子β1 基质细胞衍生因子1 CXC趋化因子受体4 

分 类 号：R692[医药卫生—泌尿科学] R332[医药卫生—外科学]