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中国临床研究英文版:2023,36(7):1027-1032
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慢性肾脏病患者肾组织USP7和自噬相关蛋白的表达及其与肾间质纤维化的关系
(1. 陕西省人民医院肾病血透中心,陕西 西安 710068;2. 洛阳市第六人民医院消化内科,河南 洛阳 471000)
Expression of USP7 and autophagy-related protein in renal tissue of chronic kidney disease patients and its relationship with renal interstitial fibrosis
摘要
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Received:October 12, 2022   Published Online:July 19, 2023
中文摘要: 目的 探讨泛素特异性蛋白酶7(USP7)和自噬相关蛋白在慢性肾脏病(CKD)患者中的表达,及与肾间质纤维化(RIF)的关系。〖HTH〗方法〓〖HTSS〗回顾性选取2021年6月至2022年1月陕西省人民医院肾病血透中心收治并行肾穿刺活检术的CKD患者55例,采用免疫组化法检测患者肾穿刺活检组织USP7及自噬相关蛋白[P62、微管相关蛋白1轻链3B(LC3B)]、RIF标志蛋白[α-平滑肌肌动蛋白(α-SMA)、纤连蛋白(FN)]的表达水平。比较不同程度RIF肾组织USP7表达的差异,分析其与实验室相关指标、α-SMA、FN及P62、LC3B的相关性。结果 依无纤维化组、轻度纤维化组、中重度纤维化组之序,CKD患者肾组织USP7表达水平递升(P<0.01),自噬相关蛋白P62表达水平递升、LC3B递降(P<0.01)。在临床指标方面,USP7表达水平与血尿素氮、肌酐、胱抑素C(CysC)、尿酸和中性粒细胞明胶酶相关脂质运载蛋白(NGAL)呈显著正相关(P<0.01),与肾小球滤过率呈显著负相关(P<0.05);在RIF标志蛋白及自噬相关蛋白方面,USP7表达水平与α-SMA、FN、P62呈显著正相关(r=0.928, P<0.01;r=0.871, P<0.01;r=0.770, P<0.01),与LC3B呈显著负相关(r=-0.668, P<0.01)。结论 USP7与细胞自噬可能是CKD患者RIF发生、发展的重要因素,USP7可能通过抑制细胞自噬促进RIF的发生。
Abstract:Objective To explore the expressions of ubiquitin-specific protease 7 (USP7) and autophagy-related proteins in renal tissues and their associations with renal interstitial fibrosis(RIF) in the patients with chronic kidney disease (CKD). Methods A total of 55 CKD patients admitted to Shaanxi Provincial Peoples Hospital and underwent renal puncture biopsy from June 2021 to January 2022 were selected retrospectively. Immunohistochemical method was used to detect the expression levels of USP7 and autophagy-related proteins [P62, microtubule-associated protein 1 light chain 3B(LC3B)], RIF marker proteins [α-smooth muscle actin (α-SMA), fibronectin (FN)] in renal biopsy tissues of patients. The differences in USP7 expression in kidney tissues with different degrees of RIF were compared, and its correlation with laboratory related indexes (α-SMA, FN, P62 and LC3B) was analyzed. Results According to the order of non-fibrosis group, mild fibrosis group and moderate to severe fibrosis group, the expression levels of USP7 and autophagy-associated protein P62 increased gradually, while LC3B decreased gradually in renal tissue of CKD patients(P<0.01). In terms of clinical indexes, the USP7 expression level was positively correlated with blood urea nitrogen, creatinine, cystatin C (CysC), uric acid and neutrophil gelatinase-associated lipocalin (NGAL)(P<0.01), while negatively correlated with glomerular filtration rate(P<0.05). In terms of RIF marker protein and autophagy-related protein, the USP7 expression level was positively correlated with α-SMA, FN and P62 (r=0.928, P<0.01; r=0.871, P<0.01; r=0.770, P<0.01), while negatively correlated with LC3B (r=-0.668, P<0.01). Conclusion USP7 and cellular autophagy may be important factors in the occurrence and development of RIF in CKD, and USP7 may promote the occurrence of RIF by inhibiting cellular autophagy.
文章编号:     中图分类号:R692 R-4    文献标志码:B
基金项目:陕西省自然科学基础研究计划项目(2021JQ-905);陕西省人民医院科技人才支持计划(2021JY-31)
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