ROBO4/ARF6信号通路在糖尿病肾病患者肾小球组织的表达及意义  

Expression and clinical significance of ROBO4/ARF6 signal pathway in renal glomerulus tissue of patients with diabetic kidney disease

作　　者：官涛[1] 郑科[1] 刘军辉[1] 祝旭飞[1] 张均[2] 黄云剑[1] 

机构地区：[1]第三军医大学新桥医院肾内科,重庆400037 [2]第三军医大学新桥医院肾内病理科,重庆400037

出　　处：《解放军医学杂志》2016年第4期267-272,共6页Medical Journal of Chinese People's Liberation Army

基　　金：国家自然科学基金(81370821);重庆市自然科学基金(cstc2013jj B10023)~~

摘　　要：目的探讨不同病理分期糖尿病肾病(DKD)患者肾小球中ROBO4/ARF6的表达情况及其与肾小球内皮细胞(MGECs)通透性的相关性。方法收集30例DKD患者肾穿刺活检标本,参考Tervaert病理分期将DKD肾组织分为早、中、晚期各10例,以10例正常肾组织标本作为对照。采用免疫组化法检测ROBO4/ARF6在MGECs中的表达,分析其与蛋白尿、血清肌酐、肾小球滤过率(e GFR)、糖化血红蛋白的相关性。结果正常MGECs中有丰富的ROBO4表达,而ARF6表达较少。DKD组ROBO4主要在MGECs中表达,而ARF6在MGECs和肾小管上皮细胞中均有表达。与正常对照组相比,DKD组ROBO4染色阳性强度明显降低(P<0.05),且随病理分期的增加阳性强度逐渐减弱;而ARF6阳性强度随DKD病理分期的增加逐渐增高(P<0.05)。ROBO4在MGECs中的阳性强度与24h蛋白尿呈负相关(r=–0.840,P<0.01),与血清肌酐呈负相关(r=–0.689,P<0.01),与糖化血红蛋白呈负相关(r=–0.660,P<0.01),与e GFR呈正相关(r=0.589,P<0.01);ARF6在MGECs中的染色强度与血清肌酐、e GFR无相关性(P>0.05),与24h蛋白尿呈正相关(r=0.603,P<0.01),与糖化血红蛋白呈正相关(r=0.582,P<0.01)。结论 DKD患者MGECs中存在ROBO4低表达和ARF6高表达,提示ROBO4/ARF6信号通路可能参与了DKD肾小球内皮、血管的病理损伤和尿蛋白的进展。Objective To investigate the expression of ROBO4/ARF6 and its correlation to glomerular endothelial cells（MGECs） permeability at each pathological stage of diabetic kidney disease（DKD）. Methods Thirty patients with DKD were enrolled（patient group）, and their renal tissues obtained by biopsy were divided into incipient, manifest and advanced stages（10 each） with Tervaert pathological staging, and confirmed normal renal tissues adjacent to the renal angiomyolipoma were assigned as control group. Immunohistochemistry method of Max Vision was used to detect the expression of ROBO4/ARF6 in the specimens, and then the correlation of the expression with the clinicopathological parameters（patients＇ Hb A1 c, albuminuria, serum creatinine, e GFR） were determined using statistical software SPSS 21.0. Results ROBO4 was abundantly but ARF6 rarely expressed in normal MGECs. In DKD patients, ROBO4 was mainly expressed in MGECs, while ARF6 was expressed in both MGECs and renal tubular epithelial cells. Compared with the control group, the positive intensity of ROBO4 in patient group decreased significantly（P〈0.05） and gradually with the increase in pathological stage, but the positive intensity of ARF6 increased gradually with the increase in DKD pathological stage（P〈0.05）. The positive intensity of ROBO4 in MGECs was negatively correlated with the contents of 24h-urinary albumin（r=–0.840, P〈0.01）, serum creatinine（r=–0.689, P〈0.01） and Hb A1c（r=–0.660, P〈0.01）, and positively correlated with e GFR（r=0.589, P〈0.01）. The staining intensity of ARF6 in MGECs showed no correlation with the contents of serum creatinine and e GFR（P〈0.05）, but was positively correlated with 24h-urinary albumin（r=0.603, P〈0.01） and Hb A1c（r=0.582, P〈0.01）. Conclusion The low expression of ROBO4 and high expression of ARF6 in MGECs of DKD patients suggest that ROBO4/ARF6 signaling pathway may participate in the DKD glomerular endothelial and vascular pathological injury and

关 键 词：糖尿病肾病 肾小球 内皮细胞 ROBO4 ARF6 免疫组织化学 

分 类 号：R587.24[医药卫生—内分泌]