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纸质出版:2017
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刘军辉,唐璐瑶,侯世会,官涛,张均,黄云剑.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[J].陆军军医大学学报(原第三军医大学学报),2017,39(01):60-66.
Liu Junhui,Tang Luyao,Hou Shihui,Guan Tao,Zhang Jun,Huang Yunjian.Expression and significance of Slit2/Robo1 signaling pathway in glomeruli of early diabetic nephropathy[J].J Amry Med Univ (J Third Mil Med Univ),2017,39(01):60-66.
刘军辉,唐璐瑶,侯世会,官涛,张均,黄云剑.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[J].陆军军医大学学报(原第三军医大学学报),2017,39(01):60-66. DOI:
Liu Junhui,Tang Luyao,Hou Shihui,Guan Tao,Zhang Jun,Huang Yunjian.Expression and significance of Slit2/Robo1 signaling pathway in glomeruli of early diabetic nephropathy[J].J Amry Med Univ (J Third Mil Med Univ),2017,39(01):60-66. DOI:
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
eGFR)>90 mL/(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eGFR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(P0.01)。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,P0.01;r=0.72,P0.01);早期DN肾小球中Slit2、 Robo1和CD31表达与eGFR呈显著正相关(r=0.78,P0.01;r=0.81,P0.01;r=0.57,P0.05);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,P0.05;r=0.49,P0.05;r=0.47,P0.05)。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 m2)] 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 (P0.01). The Slit2 or Robo1 expression was positively correlated with that of CD31 in the DN (r=0.73
P0.01; r=0.72
P0.01)
and the expression levels of Slit2
Robo1 and CD31 were positively correlated with DN patients’ eGFR (r=0.78
P0.01; r=0.81
P0.01; r=0.57
P0.05) and with DN patients’ 24-h urinary albumin excretion (r=0.46
P0.05; r=0.49
P0.05; r=0.47
P0.05). Conclusion Slit2/Robo1 signaling pathway may promote pathological angiogenesis in early DN by participating in the proliferation of glomerular endothelial cells
and then accelerate the progression of urinary protein.
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