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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 between interleukin 18 (IL-18) and IL-18 antibody (IL-18 Ab) and micro-lesion-type doxorubicin nephropathy in rats. Methods Thirty Wistar rats were randomly divided into three groups: normal control group, non-treatment group and IL-18Ab treatment group. Injection of doxorubicin (6.5 mg.kg-1) into the caudal vein resulted in an animal model of minimal-nephrotic syndrome. IL-18Ab (10μg each) was intraperitoneally injected into the IL-18Ab-treated group, and the same dose of 9 g · L-1 saline was injected into the non-treated group. The levels of 24 h urine protein were detected on days 1, 14, 28 and 42, respectively. The blood samples were collected on the 42nd day for determination of serum total cholesterol (TC), triglyceride (TG), total protein (TP), albumin Alb, BUN, SCr, IL-18, IFN-γ and TNF-α were detected by immunohistochemistry. The expression of IL-18, IFN-γ and TNF- Electron microscopy pathology. Results 24 h urine protein quantitation: The non-treatment group and the IL-18Ab treatment group began to increase on the 14th day and reached the peak on the 28th day. On the 14th, 28th and 42nd days, the non-treatment group and IL-18Ab treatment group were higher than the normal control group (Pa <0.05). On the 28th and 42nd days, IL-18Ab treatment group was lower than the non-treatment group (Pa <0.05). Serum TC and TG in non-treatment group and IL-18Ab treatment group were higher than those in normal control group (P <0.05), IL-18Ab treatment group was lower than non-treatment group (P <0.05), non-treatment group and IL-18Ab treatment group Serum TP and Alb were lower than those in the normal control group (Pa <0.05), IL-18Ab treatment group was higher than the non-treatment group (P <0.05). The levels of IL-18, IFN-γ and TNF-α in serum and IL-18, IFN-γ and TNF-α in renal tissue were significantly higher in non-treatment group and IL-18Ab treatment group than those in normal control group IL-18Ab treatment group were lower than non-treatment group (Pa <0.05). Nephridial light and electron microscopy Pathomorphology: There was no significant change in the light microscope of the three groups. Electron microscope showed that the structure of the normal control group was normal, and the lesions of the non-treated group were obvious. The lesions of the IL-18Ab treatment group were mild. Conclusion The production of IFN-γ and TNF-α mediated by IL-18 may be involved in the formation of proteinuria in doxorubicin nephropathy in patients with minimal change lesion. IL-18Ab may have some therapeutic effects on it.