抗肾小球基底膜抗体肾炎动物模型的建立及应用研究  

The Establishment and Application of Anti-GBM Antibody Induced Glomerulonephritis in Animal Model

作　　者：薛鲁[1] 杨晓倩[2] 朱峰华[2] 唐炜[2] 左建平[2] 

机构地区：[1]上海中医药大学,上海201203 [2]中国科学院上海药物研究所,上海201203

出　　处：《上海中医药大学学报》2015年第4期58-62,共5页Academic Journal of Shanghai University of Traditional Chinese Medicine

摘　　要：目的:建立稳定的抗小鼠肾小球基底膜(GBM)抗体诱导的小鼠肾炎模型,用于相关药物药效学及机制的研究。方法:1制备含抗小鼠GBM抗体的兔血清。分离获得小鼠GBM组分,制备成冻干粉免疫家兔,得到含抗小鼠GBM抗体的兔血清。2建立抗小鼠GBM抗体诱导的小鼠肾炎模型。将兔Ig G与弗氏完全佐剂(CFA)充分乳化,于C57BL/6小鼠右脚脚掌注射进行致敏,3 d后尾静脉注射兔血清进行再次免疫。3肾炎小鼠口服肾上腺皮质激素类药物醋酸泼尼松龙(PNS)进行干预治疗,口服给药14 d,2 mg·kg-1·d-1,观察小鼠蛋白尿、蛋白肌酐比、血生化的变化。结果:注射含抗小鼠GBM抗体的兔血清(200μl,300μl,500μl),成功建立小鼠肾炎模型,模型小鼠蛋白尿及血清尿素氮(BUN)水平显著升高,血清白蛋白(ALB)水平明显降低,具有统计学意义(P<0.05,P<0.01);PNS治疗后,能明显降低肾炎小鼠蛋白尿水平、蛋白肌酐比及BUN水平(P<0.05,P<0.01),缓解小鼠肾炎症状。结论:含抗小鼠GBM抗体的兔血清能够成功诱导小鼠肾炎模型,醋酸泼尼松龙能够有效发挥治疗作用,证实该模型可用于相关药物药效学及机制的研究。Objective： To establish stable anti-glomerular basement membrane （GBM） antibody induced glomerulonephritis in mice for the study of pharmacodynamics of drugs and related mechanism. Methods： ① Rabbit serum containing anti-GBM antibodies in mice were set up. GBM components from the mice were isolated for the preparation of producing rabbit serum containing anti-GBM antibodies by immunizing rabbit. ②The mice nephritis induced by anti-GBM antibody was established. C57BL/6 mice were preimmunized subcutaneously in the right foot pad with rabbit IgG in Freund＇ s adjuvant Complete（CFA） . Three days later, mice were injected intravenously with rabbit serum. ③The mice were tresated with the adrenal cortical hormone drugs of prednisone acetate （PNS） for 14 days, 2 mg/kg/day by oral administration, and then proteinuria, protein/creatinine and blood biochemical changes were observed. Results： The nephritis mice models were set up successfully by injection of rabbit serum containing anti-GBM antibodies in mice （200μl, 300μl, 500μl）. The proteinuria arid blood urea nitrogen （BUN） level significantly increased in vehicle group, and the level of serum albumin （ALB） significantly decreased （P 〈 0. 05, P 〈0.01 ）. With the treatment of PNS, the level of pi＇oteinuria, protein/ creatinine and BUN could significantly lower （P 〈 0.05, P 〈 0.01 ）, which can alleviate symptoms of glomerulonephritis in mice. Conclusion： The rabbit serum containing anti-GBM antibodies can successfully induced nephritis in mice. Oral administration of PNS show a therapeutic effect on the nephritis mice, and this confirm that anti-GBM nephtitis mice can be used in the pharmacodynamics of drugs and related mechanism research.

关 键 词：兔血清 抗肾小球基底膜抗体肾炎 醋酸泼尼松龙 动物模型 小鼠 

分 类 号：R-332[医药卫生] R277.5