NALP3／ASC／caspase-1在局灶节段性肾小球硬化肾组织中的表达变化

摘要

Objective To investigate the expression change of renal NLR family pyrin domain containing-3 protein(NALP3) in-flammasome in the nephrotic syndrome(NS) patients with focal segmental glomerulosclerosis(FSGS) and its relation with the tubu-lointerstitial pathogenic injury degree ,expression of inflammatory factors and clinical biochemical indexes .Methods Immunohisto-chemistry was used to detect the expressions of NALP3/ASC/caspase-1 and their downstream effector molecule IL-1β,IL-18 in re-nal tubular epithelial cells .The tubulointerstitial injury score and the activated macrophages F4/80 in renal interstitium of the FSGS patients and NS patiens were evaluated .The serum creatinine ,urea ,total protein ,albumin ,24 h urine protein and estimated glomer-ular filtration rate(eGFR) were observed .The correlation of tubulointerstitial injury with NALP3/ASC/caspase-1 ,IL-1β,IL-18 were respectively analyzed .Results The expression of NALP3/ASC/caspase-1 ,IL-1β,IL-18 in the renal tissue of the FSGS pa-tients was significantly increased compared with that in the control group (P<0 .01) .NALP3/ASC/capspase-1 expression was pos-itively correlated with the expression of IL-1β,IL-18(P< 0 .01) .NALP3/ASC/caspase-1 ,IL-1β,IL-18 expression was positively correlated with renal tubulointerstitial injury and the F4/80 expression intensity(P<0 .01) .NALP3/ASC/caspase-1 ,IL-1β,IL-18 was significantly positively correlated with 24 h urine protein and Scr ,and negatively correlated with the eGFR (P<0 .05) ,but had no obvious correlation with plasma urea ,plasma total protein and albumin concentrations .Conclusion The NALP3 inflammasome might participate in the pathogenic mechanism of FSGS through the activation of its downstream inflammatory factor of IL-1β,IL-18 ,the more higher its expression degree ,the more severe the renal tissue injury ,whether which could be served as the warning in-dex needs the further clinical verification .%目的：研究局灶节段性肾小球硬化（FSGS）肾病综合征（NS）患者肾组织中NALP3炎性复合体的表达变化与肾小管间质病理损害程度、炎性因子表达及临床生化指标之间的关系。方法应用免疫组化检测NS患者正常肾组织（对照组）及FSGS患者肾组织（FSGS组）肾小管上皮细胞NALP3/ASC/caspase-1及其下游效应分子IL-1β、IL-18表达变化，对肾小管间质损伤程度进行评分并检测肾小管间质活化巨噬细胞F4/80情况，收集患者血肌酐、血尿素、血浆总蛋白、清蛋白、24h尿蛋白等指标，计算肾小球滤过率（eGFR）。将NALP3/ASC/caspase-1和IL-1β、IL-18表达情况分别与肾小管间质损伤程度及各生化指标进行相关性分析。结果FSGS组患者肾小管上皮细胞NALP3/ASC/caspase-1及下游效应分子IL-1β、IL-18的表达较对照组显著增高（P＜0．01）；NALP3/ASC/caspase-1表达强度与IL-1β、IL-18呈正相关（P＜0．01）；NALP3/ASC/caspase-1和IL-1β、IL-18的表达与肾小管间质损伤程度及F4/80的表达强度呈正相关（P＜0．01），与24h尿蛋白量、血肌酐浓度呈正相关（P＜0．05），与eGFR呈负相关（P＜0．05），与尿素、血浆总蛋白、清蛋白浓度无明显相关性。结论NALP3炎性复合体通过激活IL-1β、IL-18等下游炎症因子，参与FSGS的发病机制，其表达程度越高、肾组织病变程度越重，是否能作为FSGS预后的预警指标，还需进一步的临床验证。