阿霉素小鼠肾病模型的建立及IL-18结合蛋白干预的实验研究  

Experimental study of IL-18 BP treatent in ADR-induced mice model of MCN

作　　者：董孟华[1] 刘志学[2] 孟祥辉[3] 栾希英[1] 

机构地区：[1]滨州医学院基础学院,滨州市256603 [2]滨州医学院中西医结合学院 [3]高青县人民医院外科

出　　处：《滨州医学院学报》2009年第1期13-15,共3页Journal of Binzhou Medical University

基　　金：滨州医学院科技计划(BY2006KJ10)

摘　　要：目的建立阿霉素小鼠肾病模型并探讨IL-18结合蛋白(IL-18BP)通过结合内源性IL-18对该模型的干预机制。方法昆明种小鼠30只,随机分为正常对照组、阿霉素肾病造模组(ADR-MCN组)、IL-18结合蛋白治疗组(IL-18BP治疗组)3组,用阿霉素7.5 mg/kg尾静脉注射进行造模,治疗组于第5、7、12、21天腹腔注射0.5 mg/kg剂量mIL-18BP(鼠源性IL-18结合蛋白),隔周检测尿蛋白一次,观察并记录其生命体征;42 d后心脏采血处死小鼠,分离血清ELISA法检测相关细胞因子和生化指标。结果①ADR-MCN组24 h尿蛋白定量(UPE)明显升高,与正常对照组及IL-18BP治疗组相比均有显著性差异(P<0.01)。②ADR-MCN组血清中甘油三酯(TG)、总胆固醇(TC)显著高于正常对照组、IL-18BP治疗组(P<0.01),总蛋白(TP)、白蛋白(ALB)显著低于后两者(P<0.01),尿素氮(BUN)、肌酐(Scr)含量各组间无显著性差异(P>0.05);③IL-18BP治疗组血清IL-18水平比ADR-MCN组明显降低(P<0.01),且与24hUPE呈显著正相关(r=0.708,P<0.01)。结论①昆明鼠微小病变性肾病模型建立。②IL-18BP可通过特异性结合内源性IL-18抑制其下游致炎因子的释放,对阿霉素肾病模型发挥干预作用,从而调节免疫平衡,改善肾脏功能。Objective To explore the experimental therapeutic effect machanism of IL-18BP through binding endogenous IL-18 on ADR-induced nephropathy in mice. Methods The 30 KunMing mice were divided into 3 groups randomly：Blank group,Model group （ADR-MCN group）and Therapy group（ IL-18BP group）. The Model and Therapy group were induced to nephropathy model by single injection of ADR （ 7. 5 mg/kg） through tail vena,and then the mice of Therapy group were treated with rolL-18 Binding Protein （ mIL- 18BP） with 0. 5 mg/kg on day 5,7,12 and 21. Protein in uria was measured biweekly and objective sign of mice was recorded. All mice were sacrificed through getting blood from the heart on the 42 th day ater the first injection of ADR. Correlative cytokine and biochemical parameters were detected in serum. Results ①The 24hUPE of IL-18BP treated groups was significantly decreased as compared with that in ADR - MCN group, but still was significantly increased as compared with that in normal control （ P 〈 0. 01 ）. ②In ADR-MCN group, the levels of TG and TC were higher and TP and ALB were lower than those in IL-18BP theated groups in Serum（ P 〈 0. 01 ）. The levels of BUN and Scr had no significant difference （P 〉 0. 05）. ③In IL-18 BP-treated groups , the level of IL-18 in serum was significantly decreased as compared with that in ADR-MCN group（ P 〈 0. 01） and positively correlated with 24 hUPE. Conclusions ①ADR Nephropathy Model induced. ②IL-18BP has obvious therapeutic effect to ADR nephrosis mice through specifically binding IL-18, regulating immunologic balance, strengthening renal funtion.

关 键 词：微小病变型肾病综合征 阿霉素 IL-18 IL-18结合蛋白 

分 类 号：R692[医药卫生—泌尿科学]