NALP3表达与糖尿病肾病肾间质炎症的关系

目的探讨糖尿病肾病(diabetic kidney disease,DKD)患者肾组织中NALP3的表达变化与肾小管间质炎症之间的关系。方法应用免疫组化及激光共聚焦技术检测DKD患者肾小管上皮细胞NALP3及IL-1β的表达变化及其相互关系,ELISA法检测尿液IL-1β水平,生化方法检测血清总胆固醇、低密度脂蛋白(LDL)、血肌酐(Serum creatinine,SCr)、24 h尿蛋白,计算出肾小球滤过率(estimated glomerular filtration rate,eGFR),对各指标与DKD时肾小管间质损伤、eGFR进行相关性分析。结果 DKD患者尿液IL-1β水平较对照组明显增高(P<0.05),肾小管上皮细胞NALP3及IL-1β的表达较对照组显著增高(P<0.05),且二者的表达与肾小管间质损伤显著相关(P<0.01);激光共聚焦显示DKD患者NALP3表达增高的同时伴有IL-1β的增加;NALP3及IL-1β阳性细胞比例与患者年龄、体质量指数、舒张压、LDL、24 h尿蛋白、总胆固醇无显著相关性,但与血肌酐、尿IL-1β、eGFR显著相关(P<0.01)。结论 DKD患者肾小管上皮细胞NALP3表达与炎性细胞因子IL-1β水平、肾间质损伤及肾功能改变明显相关,提示NALP3的表达变化很可能与DKD肾小管间质炎症反应存在密切关系。

Relationship between NALP3 expression and renal tubulointerstitial inflammation in diabetic kidney disease

Objective To investigate the relationship between renal tissue expression of NALP3 and renal tubulointerstitial inflammation in patients with diabetic kidney disease(DKD).Methods Thirty patients with DKD were enrolled(patient group),and the pathologically confirmed normal renal tissues adjacent to the renal angiomyolipoma or kidney transplants were assigned as a control group.Immunohistochemistry and confocal laser scanning microscopy were performed to detect the expressions of NALP3 and IL-1β in renal tubular epithelial cells and their relationship.The levels of urine IL-1β,serum total cholesterol,low density lipoprotein(LDL),serum creatinine(SCr) and 24 h urine protein were measured by ELISA.The estimated glomerular filtration rate(eGFR) was calculated and the correlations between the indicators and renal tubulointerstitial inflammation were analyzed.Results The level of IL-1β in the urine of the patient group was significantly higher than that of the control group.The expression of NALP3 and IL-1β in renal tubular epithelial cells both increased significantly in the patient group compared with those in the control group(P<0.05),and their expression was positively correlated with renal tubulointerstitial injury(r=0.66,r=0.55,P<0.001).The confocal laser scanning microscopy showed that the NALP3 expression upregulated accompanied by the increase of IL-1β expression in the DKD patients.The proportion of NALP3 and IL-1β positive cells was significantly correlated with SCr,urine IL-1β and eGFR(P<0.01),but was not correlated with the age,body mass index(BMI),diastolic pressure,LDL,24 h urine protein or serum total cholesterol.Conclusion NALP3 expression in renal tubular epithelial cells is closely related to the level of inflammatory cytokine IL-1β,renal tubulointerstitial injury and renal function changes in DKD patients,suggesting that NALP3 expression plays an important role in renal tubulointerstitial inflammation in DKD.