中文摘要：

目的研究泛素连接酶Parkin在糖尿病肾病（diabetic nephropathy,DN）患者肾组织中的表达规律及与肾小管间质损伤的关系。方法纳入2015-2016年我院收治的40例经肾活检确诊为2型DN患者,并取10例肾肿瘤切除后远端正常肾组织为对照组。采用免疫组化检测不同DN间质损伤评分肾组织的Parkin表达水平,并与临床指标、肾组织病理损伤进行相关性分析。免疫荧光共染检测肾小管Parkin的表达分别与肾间质损伤因子IL-6、TGF-β的表达及间质纤维化标志Col-Ⅳ的表达的关系。结果 Parkin主要在肾小管上皮细胞细胞质中表达,并随着DN肾小管间质损伤评分的加重而逐渐减少。Parkin表达与肾脏结构损伤（肾小球硬化、肾小管萎缩与间质纤维化、肾间质炎症）评分呈显著负相关（P〈0.01）,与肾脏功能损伤指标[尿蛋白定量、尿N-乙酰-β-氨基葡萄糖苷酶（NAG）、尿素氮、血清胱抑素C、血肌酐]呈负相关关系（P〈0.01）,与肾小球滤过率呈正相关关系（P〈0.05）。肾组织Parkin阳性肾小管细胞并不表达促炎因子IL-6、促纤维化因子TGF-β及Col-Ⅳ。结论 Parkin表达降低与DN肾间质损伤密切相关。

英文摘要：

Objective To investigate the expression of Parkin in renal tissues of patients with diabetic nephropathy（ DN） and the relationship between Parkin expression and renal tubulointerstitial injury.Methods Totally 40 patients diagnosed with type 2 DN by renal biopsy admitted in our hospital between2015 and 2016 were enrolled in this study. Ten patients with pathologically confirmed normal kidney tissues after renal tumor resection were taken as control group. Immunohistochemical examination were performed to detect the Parkin expression in renal tissues with different tubulointerstitial injury scored by interstitial fibrosis and tubular atrophy（ IFTA） classification. The expression of Parkin correlating to clinical factors and renal pathological damage was determined by Pearson and Spearman correlation analyses, respectively.Immunofluorescence staining was performed to determine the expression of Parkin,renal interstitial injury factors e. g. interleukin（ IL）-6,transforming growth factor beta（ TGF-β）,and interstitial fibrosis marker collagen Ⅳ（ Col-Ⅳ）. Results Parkin was mainly expressed in the cytoplasm of renal tubular epithelial cells,and its expression level was gradually decreased with increased IFTA score. There was a significant negative correlation between Parkin expression and renal tissue injury scores（ glomerulosclerosis,tubular atrophy and interstitial fibrosis,renal interstitial inflammation）（ P〈0. 01）. Such negative correlation wasalso found between Parkin expression and renal function injury parameters（ quantitative urinary protein,urinary N-Acetyl-β-D glucosaminidase,blood urea nitrogen,serum cystatin C,serum creatinine）,while Parkin expression was positively correlated with estimated glomerular filtration rate（ e GFR）（ P〈0. 05）.Immunofluorescence assay showed that renal tubular epithelial cells with positive expression of Parkin did not co-express IL-6,TGF-β and Col-IV. Conclusion Decreased expression of Parkin is closely related to renal tubulointers