摘要:
目的 探讨IgA肾病(IgAN)患者血清氧化应激相关指标水平与肾间质纤维化程度的关系.方法 病例来自2013年1月至2014年12月宁夏医科大学总医院经肾活检确诊的原发性IgAN患者78例,按2009年IgA肾病牛津病理分型标准中的肾小管萎缩/肾间质纤维化程度分级标准将患者分为3组:T0组(30例)、T1组(26例)和T2组(22例).选取同期在宁夏医科大学总医院体检的健康者30例为对照组.分别采用黄嘌呤氧化酶法、硫代巴比妥酸分光光度法、紫外分光法、化学比色法检测血清超氧化物歧化酶(SOD)、丙二醛(MDA)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)水平.用酶联免疫吸附法检测各组患者血清晚期氧化蛋白产物(AOPPs)、转化生长因子β1 (TGF-β1)、单核细胞趋化蛋白1(MCP-1)、转化生长因子α(TGF-α)、白细胞介素6(IL-6)、低氧诱导因子1α(HIF-1α)水平.Spearman相关分析法分析血清氧化应激相关指标水平与肾小管萎缩/肾间质纤维化传统影响因素的相关性;多元线性回归分析氧化应激相关指标与肾小管萎缩/肾间质纤维化病变程度传统影响因素的相关性.结果 T0组、T1组和T2组血清AOPPs、MDA、SOD、CAT、GSH-Px水平的差异有统计学意义(均P< 0.05),随着肾间质纤维程度的增加,AOPPs、MDA水平逐渐升高,SOD、CAT、GSH-Px水平逐渐降低(均P < 0.05).Spearman相关分析结果显示,血AOPPs水平与平均动脉压、Scr、血UA及24 h尿蛋白量呈正相关,与血总蛋白、Alb、估算肾小球滤过率呈负相关(均P< 0.01).血清AOPPs、MDA水平与TGF-β1、MCP-1、TGF-α、IL-6、HIF-1α水平呈正相关,血SOD、CAT、GSH-Px水平与TGF-β1、MCP-1、TGF-α、IL-6、HIF-1α水平呈负相关(均P<0.05).多元线性回归分析结果显示,IgAN患者肾间质纤维化的病变程度与血AOPPs水平呈正相关(β=0.285,P=0.001),与CAT(β=-0.346,P<0.001)、GSH-Px (β=-0.303,P<0.001)水平呈负相关.结论 IgAN患者血清氧化应激指标水平升高,且与肾间质纤维化程度呈正相关,提示氧化应激可能参与了肾间质纤维化的发生发展过程.%Objective To investigate the relationship between serum levels of oxidative stress indicators and the degree of renal interstitial fibrosis in patients with IgA nephropathy (IgAN).Methods Seventy eight patients with confirmed primary IgAN in General Hospital of Ningxia Medical University from January 2013 to December 2014 were enrolled.The patients were divided into T0 group (n=30),T1 group (n=26) and T2 group (n=22) according to the grade of tubular atrophy/interstitial fibrosis of Oxford pathological classification criteria for IgAN in 2009.Meanwhile,thirty cases of health examiner were enrolled as control subjects.The levels of serum malondialdehyde (MDA),superoxide dismutase (SOD),catalase (CAT) and glutathione peroxidase (GSH-Px) were detected by xanthine oxidase method,thiobarbituric acid spectrophotometry method,ultraviolet spectrophotometry method,chemical colorimetric method,respectively.The levels of serum advanced oxidation protein products (AOPPs),transforming growth factor beta 1 (TGF-β1),monocyte chemotactic protein 1 (MCP-1),transforming growth factor alpha (TGF-α),interleukin 6 (IL-6) and hypoxia inducible factor 1 alpha (HIF-1α) were detected by enzyme linked immunosorbent assay (ELISA) in all groups.Spearman correlation analysis was used to analyze the correlation between serum oxidative stress indicators and traditional risk factors of tubular atrophy/renal interstitial fibrosis.Multivariable linear regression analysis was used to analyze the correlation between oxidative stress indicators and degree of renal tubular atrophy/renal interstitial fibrosis.Results There were differences in serum levels of AOPPs,MDA,SOD,CAT and GSH-Px in IgAN patients with different degrees of renal interstitial fibrosis (all P < 0.05).With the increase of renal interstitial fibrosis,the levels of AOPPs and MDA increased gradually,while the levels of SOD,CAT and GSH-Px decreased gradually.Serum AOPPs,MDA,SOD,CAT,GSH-Px concentration in IgAN patients were correlated with the mean arterial pressure (MAP),total blood protein (TP),albumin (Alb),Scr,uric acid (UA),24-hour urinary protein volume and estimated glomerular filtration rate (eGFR).Multivariate regression analysis showed that the AOPPs levels of blood were positively correlated with MAP,Scr,UA and 24-hour urinary protein (all P < 0.01),and negatively correlated with TP,Alb,eGFR (all P < 0.05).The serum levels of AOPPs and MDA in IgAN patients were positively correlated with the levels of TGF-β1,MCP-1,TGF-α,IL-6 and HIF-1α.The levels of SOD,CAT and GSH-Px were negatively correlated with the levels of TGF-β1,MCP-1,TGF-α,IL-6 and HIF-1α.Multivariate stepwise regression analysis showed that the degree of renal interstitial fibrosis in IgAN patients was positively correlated with serum AOPPs level (β=0.285,P=0.001),negatively correlated with CAT (β=-0.346,P < 0.001),GSH-Px (β=-0.303,P <0.001).Conclusions The level of serum oxidative stress in IgAN patients is elevated and positively correlated with the degree of renal interstitial fibrosis,suggesting that oxidative stress may be involved in the occurrence and development of renal interstitial fibrosis.