NLRP3炎性体在糖尿病肾病肾间质炎症反应中的作用

Effect of NLRP3 inflammasome on diabetic nephropathy renal interstitial inflammation

目的探讨NLRP3炎性体在糖尿病肾病肾间质炎症反应中的作用。方法选择2014年6月—2015年5月浙江省人民医院2型糖尿病肾病患者50例作为糖尿病肾病组,同期肾脏错构瘤手术切除患者50例作为对照组。比较2组患者的临床资料、尿IL-18和尿IL-1β水平、肾小管上皮细胞NLRP3、P2X4、IL-18和IL-1β的表达,分析糖尿病肾病肾间质炎症和肾小管上皮细胞NLRP3、P2X4、IL-18和IL-1β表达的相关性,糖尿病肾病肾小管上皮细胞NLRP3、P2X4免疫组化表达评分和尿IL-18、IL-1β水平的相关性。结果糖尿病肾病组的尿蛋白定量、空腹血糖、甘油三酯、总胆固醇和低密度脂蛋白均高于对照组(P<0.05)。糖尿病肾病组尿IL-18和尿IL-1β水平均高于对照组(P<0.05)。糖尿病肾病组肾小管上皮细胞中NLRP3、P2X4、IL-18和IL-1β呈高表达,对照组肾小管上皮细胞中NLRP3、P2X4、IL-18和IL-1β呈低表达或不表达。糖尿病肾病组肾小管上皮细胞NLRP3、P2X4、IL-18和IL-1β的表达评分均明显高于对照组(P<0.05)。糖尿病肾病肾间质炎症和肾小管上皮细胞NLRP3、P2X4、IL-18和IL-1β表达均呈正相关(P<0.05)。糖尿病肾病肾小管上皮细胞NLRP3、P2X4免疫组化表达评分和尿IL-18、IL-1β水平均呈正相关(P<0.05)。结论 P2X4可能通过激活NLRP3炎性体,调控炎性细胞因子,引起糖尿病肾病肾间质炎症反应。

Objective To explore the effect of NLRP3 inflammasome on diabetic nephropathy renal interstitial inflamma- tion. Methods From Zhejiang provincial people＇ s hospital type 2 diabetic nephropathy,50 patients were selected as dia- betic nephropathy group, kidney hamartoma surgery 50 patients as control group. The clinical data, urinary IL-18 and IL-1β levels, renal tubular epithelial cells NLRP3, P2X4, IL-18 and IL-1β expression were compared in two groups. The cor- relation between diabetic nephropathy renal interstitial inflammation and tubular epithelial cells NLRP3 ,P2X4 ,IL-18 and IL-1β expression, and the correlation between diabetic nephropathy renal tubular epithelial cells NLRP3, P2X4 immuno- histochemical expression score and urine IL-18 ,IL-1β levels were analyzed. Results The urinary protein excretion,fast- ing blood glucose, triglycerides, total cholesterol and low density lipoprotein in diabetic nephropathy group were higher than that of control group（P 〈0.05 ）. The urine IL-18 and urine IL-1β levels of diabetic nephropathy were higher than that of control group（ P 〈 0.05 ）. The renal tubular epithelial cells NLRP3, P2X4, IL-18 and IL-1β expression of diabetic nephropathy group were high, the renal tubular epithelial cells NLRP3, P2X4, IL-18 and IL-1β expression of diabetic ne- phropathy group were low expression or not expression. The renal tubular epithelial cells NLRP3, P2X4, IL-18 and IL-1β expression scores of diabetic nephropathy group were significantly higher than that of control group （ P 〈 0.05 ）. Diabetic nephropathy renal interstitial inflammation was positively correlated with tubular epithelial cells NLRP3 ,P2X4, IL-18 and IL-1β expression（ P 〈0.05 ）. Diabetic nephropathy renal tubular epithelial cells NLRP3, P2X4 immunohistochemical expression score were positively correlated with urine IL-18, IL-1β levels（ P 〈 0.05 ）. Conclusion P2X4 possibly activates NLRP3 inflammatory body, regulate inflammatory cytokines, and causes diabetic nephropathy renal interstitial inflammation.