Slit2/Robo1信号通路蛋白在早期糖尿病肾病肾小球中的表达及临床意义  

Expression and significance of Slit2/Robo1 signaling pathway in glomeruli of early diabetic nephropathy

作　　者：刘军辉[1] 唐璐瑶[1] 侯世会 官涛[1] 张均[1] 黄云剑[1] Liu Junhui Tang Luyao Hou Shihui Guan Tao Zhang Jun Huang Yunjian(Department of Nephrology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, Chin)

机构地区：[1]第三军医大学新桥医院肾内科,重庆400037

出　　处：《第三军医大学学报》2017年第1期60-66,共7页Journal of Third Military Medical University

基　　金：国家自然科学基金面上项目(81370821);重庆市自然科学基金重点项目(CSTC2013jjB10023)~~

摘　　要：目的探讨早期糖尿病肾病(diabetic nephropathy,DN)肾小球中Slit2和Robo1的表达与肾小球内皮细胞增生的关系及临床意义。方法收集符合Tervaert’s糖尿病肾病病理分型Ⅰ~Ⅱa期,患者24 h尿蛋白>30 mg且<500 mg,肾小球滤过率(estimate glomerular filtration rate,e GFR)>90 m L/(min·1.73 m2)等纳入标准的19例2型糖尿病DN标本,以及15例正常肾组织手术标本,采用HE染色、PAS染色和电镜观察DN肾小球组织形态结构的变化,免疫组化检测Slit2、Robo1和血管内皮细胞标记物CD31在肾小球中的表达,分析DN肾小球中Slit2和Robo1与CD31表达的相关性,以及Slit2、Robo1和CD31的表达与24 h尿蛋白以及e GFR的相关性。结果早期DN存在肾小球肥大、系膜基质轻度增多、基底膜增厚、毛细血管扩张、血管内皮细胞增大和增多等典型早期DN病理特征。Slit2表达于肾小球血管内皮、肾小管上皮和系膜细胞区域;Robo1表达于肾小球血管内皮、肾小管上皮和足细胞区域。与正常肾组织相比,早期DN肾小球中CD31的表达水平显著增高。早期DN肾小球中Slit2和Robo1的表达较正常肾组织也显著性增高(P<0.01)。相关性分析显示,早期DN肾小球中Slit2和Robo1的表达与CD31表达呈显著正相关(r=0.73,P<0.01;r=0.72,P<0.01);早期DN肾小球中Slit2、Robo1和CD31表达与e GFR呈显著正相关(r=0.78,P<0.01;r=0.81,P<0.01;r=0.57,P<0.05);早期DN肾小球中Slit2、Robo1和CD31表达与24 h尿蛋白也呈显著正相关(r=0.46,P<0.05;r=0.49,P<0.05;r=0.47,P<0.05)。结论 Slit2/Robo1信号通路可能通过参与早期DN肾小球内皮细胞增生促进病理性血管生成,从而加速蛋白尿的进展。Objective To investigate the expression of Slit2/Robo1 and its relationship with the proliferation of glomerular endothelial cells in the patients with early diabetic nephropathy （DN）, and evaluate the clinical significance of the signal pathway. Methods Renal tissues of 19 patients with early DN [at classes Ⅰ～Ⅱa of Tervaert’s classification, 24- h urinary albumin excretion between 30 and 500 mg, estimated glomerular filtration rate （eGFR） 〉90 mL/（ min·1.73 m^2）] were collected, and another 15 normal renal tissues were also harvested as control. HE staining, PAS staining and electron microscopy were used to observe the glomerular morphology of the obtained tissues. Immunohistochemical staining was employed to detect the expression of Slit2, Robo1 and CD31 in the glomerular specimens, and then the correlation of the expression of Slit2 and Robo1 with CD31 was analyzed, and the correlation of their expression with 24-h urinary albumin excretion and eGFR was also analyzed. Results Pathological observation displayed that typical morphological features of early DN, including glomerular hypertrophy, slightly expanded mesangial matrix, thickened glomerular basement membrane, telangiectasia, and enlarged and increased vascular endothelial cells were seen in the DN group. Slit2 was expressed in the vascular endothelial cells, tubule epithelial cells and mesangial cells. Robo1 was expressed in the vascular endothelial cells, tubule epithelial cells and podocyte cells. CD31 was highly expressed in the renal tissues from the DN patients than the non-diabetic control. The expression levels of Slit2 and Robo1 were also strongly expressed in the DN group than the non-diabetic control （P〈0.01）. The Slit2 or Robo1 expression was positively correlated with that of CD31 in the DN （r=0.73, P〈0.01; r=0.72, P〈0.01）, and the expression levels of Slit2, Robo1 and CD31 were positively correlated with DN patients’ eGFR （r=0.78, P〈0.01; r=0.81, P〈0.01; r=0.57, P〈0.05） and with DN patients�

关 键 词：糖尿病肾病 肾小球内皮细胞 血管生成 SLIT2 ROBO1 CD31 

分 类 号：R363.21[医药卫生—病理学] R587.2[医药卫生—基础医学]