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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。
Objective To investigate the relationship between the expression of NALP3 in renal tissue and the tubulointerstitial inflammation in patients with diabetic kidney disease (DKD). Methods The expressions of NALP3 and IL-1β in renal tubular epithelial cells of DKD patients were detected by immunohistochemistry and laser confocal laser scanning microscope. The levels of IL-1β in urine were detected by ELISA. The levels of serum total cholesterol and low density lipids Serum creatinine (SCr) and 24 h urinary protein (LDL), serum glomerular filtration rate (eGFR) were calculated. For each index and tubulointerstitial injury in DKD, eGFR Correlation analysis. Results The level of IL-1β in urine of DKD patients was significantly higher than that of the control group (P <0.05). The expression of NALP3 and IL-1β in renal tubular epithelial cells was significantly higher than that in the control group (P <0.05) (P <0.01). Confocal laser scanning showed that the expression of NALP3 increased with the increase of IL-1β in DKD patients. The proportion of NALP3 and IL-1β positive cells was positively correlated with age, body mass index, diastolic blood pressure, LDL , 24 h urine protein and total cholesterol, but not with serum creatinine, urinary IL-1β and eGFR (P <0.01). Conclusion The expression of NALP3 in renal tubular epithelial cells of DKD patients is significantly correlated with the levels of inflammatory cytokines IL-1β, renal interstitial injury and renal function. It suggests that there is a close relationship between the expression of NALP3 and the tubulointerstitial inflammatory reaction in DKD.