白细胞介素18在激素耐药型肾病综合征外周血单个核细胞中的表达及意义

Interleukin-18 expression in peripheral blood mononuclear cells in children with steroid-resistant nephrotic syndrome

目的通过研究原发性肾病综合征(PNS)患儿血清白细胞介素18(IL-18)水平及其在外周血单个核细胞(PBMC)中的表达,探讨IL-18在激素耐药型肾病综合征(SRNS)发生、发展中的可能机制。方法采用ELISA法及RT-PCR法测定40例正常儿童及39例激素敏感型肾病综合征(SSNS)、27例SRNS血清IL-18蛋白水平及PBMC mRNA表达。双缩脲法检测24h尿蛋白量。全自动生化分析仪检测血清总胆固醇(T-Ch)、甘油三酯(TG)、低密度脂蛋白(LDL)、总蛋白(TP)及白蛋白(Alb)含量。结果①与正常对照组相比,治疗前SSNS、SRNS血清IL-18蛋白水平及PBMCIL-18 mRNA表达均明显增高(P<0.05);与SSNS相比,SRNS上述指标均增高(P<0.05);SSNS及SRNS之间血清Alb,TP,T-Ch,TG水平及24h尿蛋白量差异无显著性(P>0.05),SRNS血清LDL水平较SSNS高(P<0.05)。②治疗后SRNS组血清IL-18蛋白水平及PBMCIL-18 mRNA表达均高于SSNS组及正常对照组(P<0.05);SSNS组与正常对照组比较差异无显著性(P>0.05)。③治疗后SSNS组血清IL-18蛋白水平及PBMCIL-18 mRNA表达较治疗前明显下降(P<0.05)。而SRNS组治疗前、后无明显变化(P>0.05)。结论PNS激素耐药与IL-18血清水平及PBMC mRNA表达明显升高有关,IL-18的过度分泌在SRNS的发生发展中发挥一定作用。

Objective To examine serum concentration of interleukin-18 （IL-18） and IL-18 mRNA expression in peripheral blood mononuclear cells （PBMCs） in children with primary nephrotic syndrome （PNS） and explore the possible role of IL-18 in steroid-resistant nephrotic syndrome （SRNS）. Methods Sixty-six children with newly diagnosed PNS, including 39 cases of steroid sensitive nephrotic syndrome （SSNS） and 27 eases of SRNS, were enrolled. Forty healthy children were used as a normal control group. Blood samples were collected before and 8 weeks after glucocortieoid treatment. Serum concentration of IL-18 was measured using ELISA. IL-18 mRNA expression in PBMCs was detected by the RT-PCR method. The amount of 24-hr urine protein was measured by the biuret method. Serum contents of total cholesterol （T-Ch）, triglyceride （TG）, low density lipoprotein （LDL）, total protein （TP）, and albumin （Alb） were measured by the automatic biochemistry analyzer. Results Serum concentration of IL-18 and IL-18 mRNA expression in PBMCs in the SSNS and the SRNS groups were significantly higher than those in the normal control group before treatment （P 〈 0.05 ）. The SRNS group had increased serum protein concentration of IL-18 and IL-18 mRNA expression in PBMCs compared with the SSNS group before treatment （ P 〈 0.05 ）. Serum LDL content in the SRNS group was also significantly higher than that in the SSNS group before treatment （P 〈 0. 05 ）. After treatment, serum concentration of IL-18 and IL-18 mRNA expression in PBMCs in the SRNS group were significantly higher than those in the SSNS and the normal control groups （P〈0.05）. Serum concentration of IL-18 and IL-18 mRNA expression in PBMCs in the SSNS group were significantly reduced after treatment, but the alterations of IL-18 were not observed in the SRNS group after treatment. Conclusions SRNS was associated with increased serum IL-18 concentration and IL-18 mRNA expression in PBMCs. Overproduction of IL-18 may play a role in the development of SRNS.