维生素D受体在IgA肾病患者肾脏中的表达及其与肾纤维化的关系
The Expression of Vitamin D Receptor in the Kidneys of Patients with IgA Nephropathy and its Relationship with Renal Fibrosis
周苏雅 1王昱 1陈凯 1汪丽珍 1缪妙 1鲍晓荣1
作者信息
- 1. 复旦大学附属金山医院肾内科(上海 201508)
- 折叠
摘要
目的:探讨维生素D受体(VDR)在IgA肾病患者肾脏中的表达及其与肾纤维化的关系.方法:收集42例肾穿刺活检病理证实为IgA肾病患者的血清、尿液及肾组织标本,根据IgA肾病牛津分型,按照肾小管萎缩/间质纤维化程度分为轻度纤维化组(T0组)及中重度纤维化组(T1组),采用酶联免疫吸附法(ELISA)检测患者血清维生素D水平,运用免疫组化技术检测肾组织维生素D受体、纤连蛋白(FN)、转化生长因子-β1(TGF-β1)的表达.结果:(1)T1组患者24 h尿蛋白定量、血肌酐、血尿素氮、血尿酸水平显著高于T0组患者,血白蛋白、估算肾小球滤过率(eGFR)水平、血维生素D水平显著低于T0组患者;(2)T1组患者肾组织VDR的表达显著低于T0组,FN、TGF-β1的表达显著高于T0 组;(3)相关性分析显示:血维生素D水平与eGFR、VDR呈显著正相关,与24 h尿蛋白定量、TGF-β1、血尿素氮呈显著负相关;肾组织VDR与血维生素D水平、eGFR呈显著正相关,与FN、TGF-β,呈显著负相关;肾组织FN与TGF-β1、24 h尿蛋白定量、血肌酐、血尿素氮呈显著正相关,与VDR、eGFR呈显著负相关.结论:IgA肾病患者肾组织中VDR表达与肾纤维化程度有关,使用维生素D受体激动剂可能是改善IgA肾病肾纤维化的有效措施,其改善IgA肾病肾间质纤维化的机制之一是其对TGF-β1信号通路的调控作用.
Abstract
Objective:To explore the expression of vitamin D receptor(VDR)in the kidneys of patients with IgA nephropa-thy and its relationship with renal fibrosis.Methods:Serum、urine and renal tissue specimens were collected from 42 patients con-firmed to have IgA nephropathy by renal biopsy.According to the Oxford classification of IgA nephropathy,the patients were divided into mild fibrosis group(T0 group)and moderate to severe fibrosis group(T1 group)based on the degree of tubular atrophy/intersti-tial fibrosis.Enzyme-linked immunosorbent assay(ELISA)was used to detect serum vitamin D levels in patients,and immunohisto-chemistry was performed to detect the expression of VDR,fibronectin(FN),and transforming growth factor-β1(TGF-β1)in renal tissues.Results:(1)The levels of 24-hour urine protein quantification,serum creatinine,serum urea nitrogen,and serum uric acid were significantly higher in the T1 group than in the T0 group.The levels of serum albumin,estimated glomerular filtration rate(eGFR)and serum vitamin D were significantly lower in the T1 group than in the T0 group.(2)The expression of VDR in the renal of the T1 group was significantly lower,while the expression of FN and TGF-β1 was significantly higher than in the T0 group.(3)Correlation analysis reveals that the levels of serum vitamin D is significantly positively correlated with eGFR and the expression of VDR in renal tissue,and significantly negatively correlated with 24-hour urine protein quantification,serum urea nitrogen,and the expression of TGF-β1 in renal tissue;Additionally,the expression of VDR in renal tissue is significantly positively correlated with serum vitamin D levels and eGFR,and significantly negatively correlated with the expression of FN and TGF-β1 in renal tissue;Fur-thermore,the expression of FN in renal tissue is significantly positively correlated with 24-hour urine protein quantification,serum creatinine,serum urea nitrogen,and the expression of FN in renal tissue,and significantly negatively correlated with eGFR and the expression of VDR in renal tissue.Conclusion:The expression of VDR in renal tissue of IgA nephropathy patients is associated with the degree of renal fibrosis.The use of vitamin D receptor agonists may be an effective measure to improve renal fibrosis in IgA ne-phropathy.One of the mechanisms by which it improves interstitial fibrosis in IgA nephropathy is its regulatory effect on the TGF-β1 signaling pathway.
关键词
IgA肾病/维生素D受体/肾纤维化/转化生长因子-β1Key words
IgA nephropathy/Vitamin D receptor/Renal fibrosis/Transforming growth factor-β1引用本文复制引用
基金项目
上海市金山区卫生健康委员会项目(JSKJ-KTQN-2020-02)
出版年
2024
NETL
NSTL
万方数据