白细胞介素-18和白细胞介素-18抗体与大鼠微小病变型多柔比星肾病的关系

Relationship of Interleukin-18 and Interleukin-18 Antibody in Adriamycin-Induced Model of Minimal Change Nephritic Syndrome

目的探讨IL-18和IL-18抗体(IL-18 Ab)与大鼠微小病变型多柔比星肾病的关系。方法将30只Wistar大鼠随机分为3组:正常对照组、非治疗组、IL-18Ab治疗组。尾静脉注射多柔比星(6.5 mg.kg-1)造成微小病变型肾病综合征动物模型。其中IL-18Ab治疗组腹腔注射IL-18Ab(每只10μg),非治疗组注射等量9 g.L-1盐水,正常对照组大鼠予尾静脉注射等量9 g.L-1盐水。分别于第1、14、28及42天检测其24 h尿蛋白水平,第42天心脏取血测其血清总胆固醇(TC)、三酰甘油(TG)、总蛋白(TP)、清蛋白(Alb)、BUN、SCr、IL-18、干扰素-γ(IFN-γ)及TNF-α水平,取其肾组织进行免疫组织化学分析IL-18、IFN-γ、TNF-α的表达及光、电镜病理形态。结果 24 h尿蛋白定量:非治疗组和IL-18Ab治疗组第14天开始增加,第28天达高峰;第14、28、42天非治疗组和IL-18Ab治疗组均高于正常对照组(Pa<0.05);第28、42天IL-18Ab治疗组低于非治疗组(Pa<0.05)。非治疗组和IL-18Ab治疗组血清TC和TG均高于正常对照组(Pa<0.05),IL-18Ab治疗组低于非治疗组(P<0.05);非治疗组和IL-18Ab治疗组血清TP和Alb低于正常对照组(Pa<0.05),IL-18Ab治疗组高于非治疗组(P<0.05)。血清IL-18、IFN-γ、TNF-α水平和肾组织IL-18、IFN-γ、TNF-α表达:非治疗组和IL-18Ab治疗组均高于正常对照组(Pa<0.05),IL-18Ab治疗组均低于非治疗组(Pa<0.05)。肾组织光、电镜病理形态:3组光镜无明显改变,电镜:正常对照组结构正常,非治疗组病变明显,IL-18Ab治疗组病变轻微。结论 IL-18介导IFN-γ、TNF-α的产生,可能参与微小病变型大鼠多柔比星肾病蛋白尿的形成,且IL-18Ab对其有部分治疗作用。

Objective To investigate the relationship of interleukin-18（IL-18） and IL-18 antibody（IL-18Ab） in the adriamycin（ADR）-induced model of minimal change nephritic syndrome（MCNS）.Methods Thirty rats were divided randomly into 3 groups：normal control group,non-treatment group and treatment group.Wistar rats were induced to the model of MCNS by single injection of ADR（6.5 mg·kg-1） though tail vena.The rats in non-treatment group and normal control group were induced by injection of equal volume of physiological saline solution.Urine protein was measured on the 1st,14th,28th and 42nd day.Serum total cholesterol（TC）,triacylglycerol（TG）,serum total protein（TP）,albumin（Alb）,urea nitrogen（BUN）,creatinine（SCr）,IL-18,interferon-γ（IFN-γ） and tumor necrosis factor-α（TNF-α） were analyzed when all rats were sacrificed on the 42nd day after the first injection of ADR.Expressions of IL-18,IFN-γ and TNF-α in kidney were analyzed with immunohistochemistry and the renal histological changes were observed under light microscope and electron microscope.Results Proteinuria appeared in the second week and had peak concentration in the fourth week.Proteinuria in control group was significantly low on the 14th,28th,42nd day（Pa〈0.05）,and that in treatment group was lower than non-treatment group on the 28th,42nd day（Pa〈0.05）.Serum TC and TG in non-treatment group and treatment group were significantly higher than those in normal control group（Pa〈0.05）,whereas those in treatment group were significantly lower than those in non-treatment group（P〈0.05）.However,serum TP and Alb in non-treatment group and treatment group were significantly lower than those in normal control group（Pa〈0.05）,whereas those in treatment group were significantly higher than those in non-treatment group（Pa〈0.05）.In addition,the expressions of IL-18,IFN-γ and TNF-α in nephridial tissue and peripheral blood in non-treatment group and treatment group were markedly increased（Pa〈0.05）,and those in treatment group were significantly decreased than those in non-treatment group（Pa〈0.05）.Three groups had no obvious differences under light microscope.However,under electron microscope,non-treatment group had the prominent lesions while treatment group showed minimal change.Conclusions IL-18 may parti-cipate in the pathogenesy of proteinuria in the rats model of MCNS.The action was mediated by production of IFN-γ,TNF-α and IL-18Ab may have therapeutical effect to a certain degree.