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目的研究糖尿病肾病(DN)患者肾组织足细胞损伤和葡萄糖调节蛋白78(GRP78)及尿蛋白量之间的关系。方法回顾性分析48例经肾活检确诊为DN患者的临床资料,根据尿蛋白量将患者分为>3.5 g/d组(n=31)和<3.5 g/d组(n=17)。对肾组织行威廉姆斯肿瘤蛋白-1(WT-1)免疫组织化学染色,冰冻肾组织行synap-topodin、GRP78免疫荧光双染色,在激光共聚焦显微镜下观察。结果尿蛋白量>3.5 g/d组的足细胞密度为0.10个/μm2,明显低于尿蛋白量<3.5 g/d组的0.15个/μm2(P=0.003),足细胞密度与尿蛋白量呈负显著相关(P=0.005)。肾小球Synaptopodin及GRP78表达呈线样或颗粒状沿基底膜排列,尿蛋白量与synaptopodin(P=0.004)和GRP78(P=0.001)表达具有显著负相关。结论随着尿蛋白量增加,DN患者的足细胞损伤程度随之加重,伴有内质网应激适应性调节能力下降。
Objective To investigate the relationship between renal podocyte injury and the expression of glucose regulatory protein 78 (GRP78) and urinary protein in patients with diabetic nephropathy (DN). Methods The clinical data of 48 patients with DN diagnosed by renal biopsy were retrospectively analyzed. The patients were divided into 3.5 g / d group (n = 31) and 3.5 g / d group (n = 17) according to urinary protein content. The renal tissues were stained with Williams Tumor Protein-1 (WT-1) immunohistochemically. Synaptic mesoderm and GRP78 double immunofluorescence staining were performed in frozen-thawed kidneys and observed under laser scanning confocal microscopy. Results The podocyte density of urinary protein> 3.5 g / d was 0.10 / μm 2, which was significantly lower than 0.15 / μm 2 (P = 0.003) of urinary protein level <3.5 g / d There was a significant negative correlation (P = 0.005). Glomerular Synaptopodin and GRP78 expressions were arranged in a linear or granular pattern along the basement membrane. Urine protein content was significantly negatively correlated with the expression of synaptopodin (P = 0.004) and GRP78 (P = 0.001). Conclusion With the increase of urinary protein, the degree of podocyte injury in DN patients aggravates with the decrease of adaptive regulation of endoplasmic reticulum stress.