炎症相关因子TLR4 NF-κB在特发性膜性肾病肾组织中的表达及临床意义

Expression and Clinical Significance of the Inflammation-Related Factors TLR4 and NF-κB in Renal Tissue of Idiopathic Membranous Nephropathy

目的:研究炎症相关因子Toll样受体4(TLR4)、核转录因子-kappa B(NF-κB)在特发性膜性肾病(IMN)患者肾组织的表达水平,探讨炎症因子TLR4、NF-κB在IMN发病过程中的临床意义。方法:本研究纳入于蚌埠医学院第一附属医院肾病科经肾活检初次诊断为IMN的患者45例为特发性膜性肾病组(IMN组),同期选取因肾挫伤、肾肿瘤或输尿管肿瘤等行肾脏切除留取健康肾脏组织20例为正常对照组(NC组)。收集两组相关临床指标并分析比较两组间差异性。采用免疫组化的方法分别检测炎症因子TLR4、NF-κB在两组肾组织中的表达,并进行平均光密度值分析,比较两组间炎症因子表达差异。将IMN组分为纤维化组29例,无纤维化组16例,分析比较两组间炎症因子表达的差异性,了解炎症在肾间质纤维化中的作用。应用Pearson相关性分析两组炎症因子之间及其与临床指标间的相关性。结果:IMN组患者肾组织中TLR4、NF-κB的表达水平显著高于NC组(P<0.01)。IMN纤维化组TLR4、NF-κB表达明显强于无纤维化组(P<0.05)。相关性分析显示:TLR4与NF-κB两者之间密切相关(P<0.01)。TLR4与血清白蛋白、高密度脂蛋白呈负相关(P<0.01),与24h尿蛋白定量、血清胆固醇、低密度脂蛋白呈正相关(P<0.05、P<0.01)。NF-κB与血清白蛋白、高密度脂蛋白呈负相关(P<0.05),与24h尿蛋白定量呈正相关(P<0.05)。结论:炎症因子TLR4、NF-κB在IMN肾组织中表达水平上调,且两者之间相互作用,引起肾组织细胞损伤,导致肾间质纤维化,参与了IMN的发生、发展。

Objective:To investigate the expression levels of inflammation-related factors toll-like receptor 4(TLR4)and nuclear transcription factor-kappa B(NF-κB)in renal tissues of patients with idiopathic membranous nephropathy(IMN)and to explore the clinical significance of the inflammatory factors TLR4 and NF-κB in the pathogenesis of IMN.Methods:In this study,45 patients who were initially diagnosed with IMN by renal biopsy in the Department of Nephrology of the First Affiliated Hospital of Bengbu Medical College were included in the group of idiopathic membranous nephropathy(IMN group),and 20 patients who had nephrectomy for renal contusion,renal tumor or ureteral tumor and left healthy kidney tissues in the same period were selected as the normal control group(NC group).The relevant clinical indexes were collected and analyzed to compare the differences between the two groups.The expressions of inflammatory factors TLR4 and NF-κB in the kidney tissues of the two groups were detected by immunohistochemistry,and the mean optical density values were analyzed to compare the differences in inflammatory factor expressions between the two groups.The IMN group was divided into 29 cases in the fibrosis group and 16 cases in the no-fibrosis group,and the differences in inflammatory factor expression between the two groups were analyzed and compared to understand the role of inflammation in renal interstitial fibrosis.Pearson correlation analysis was applied between the two groups of inflammatory factors and their correlation with clinical indices.Results:The renal tissue expression levels of TLR4 and NF-κB were significantly higher in the IMN group than in the NC group(P<0.01).The expression of TLR4 and NF-κB was significantly stronger in the IMN fibrosis group than in the group without fibrosis(P<0.05).Correlation analysis revealed a close correlation between TLR4 and NF-κB(P<0.01).The TLR4 was negatively associated with serum albumin and high density lipoprotein(P<0.01)and positively associated with urinary protein quantification,serum cholesterol,and low density lipoprotein(P<0.05,P<0.01).The NF-κB was negatively associated with serum albumin and high density lipoprotein(P<0.05)and positively associated with 24-hour urinary protein quantification(P<0.05).Conclusion:The expression level of inflammatory factors TLR4 and NF-κB are upregulated in IMN kidney tissue,and the interaction causes cell damage in renal tissue,leading to renal interstitial fibrosis,which is involved in the occurrence and development of IMN.