应用抗肾小球基底膜抗体的中和性单克隆抗体治疗抗肾小球基底膜肾炎大鼠的实验研究  

Experimental study of application of anti-glomerular basement membrane antibodies neutralizing monoclonal antibody on anti-glomerular basement membrane nephritis rats

作　　者：肖静[1] 刘章锁[1] 聂志勇[1] 王雅楠[1] 赵国强[2] 

机构地区：[1]郑州大学第一附属医院肾内科,450052 [2]郑州大学基础医学院微生物学与免疫学实验室

出　　处：《中华肾脏病杂志》2010年第9期708-713,共6页Chinese Journal of Nephrology

基　　金：国家卫生部资助项目（WKJ2007-2-033）;河南省医学科技攻关重大项目（200701006） 作者单位： （肖静、刘章锁、聂志勇、王雅楠）;郑州大学基础医学院微生物学与免疫学实验室（赵国强）通信作者：刘章锁,Email：[e-mail]

摘　　要：目的 应用抗肾小球基底膜（GBM）抗体的中和性单克隆抗体注射抗GBM肾炎大鼠,观察各种生化指标及肾脏病理学的变化.方法 将Wistar大鼠随机分为5组,每组9只：（1）肾炎模型组：经尾静脉注入人抗GBM抗体;（2）正常对照Ⅰ组：经尾静脉注入非抗体性的健康人IgG;（3）对照Ⅱ组：经尾静脉注入抗GBM抗体的中和性单克降抗体;（4）干预Ⅰ组：经尾静脉注入人抗GBM抗体,第7天后再经尾静脉注入抗GBM抗体的中和性单克隆抗体（1.5ml/100 g）;（5）干预Ⅱ组：经尾静脉注入人抗GBM抗体,第14天后再经尾静脉注入抗GBM抗体的中和性单克隆抗体.分别在实验后第7、14、21天观察大鼠24 h尿蛋白量、BUN、Scr和肾组织病理学的变化.结果 第21天干预Ⅰ组尿蛋白量为（16.62±5.53）g/d、BUN为（11.53±2.26）mmol/L、Scr为（102.46±16.86）μmol/L,均显著低于肾炎模型组（P＜0.05）;干预Ⅱ组较肾炎模型组也有所降低,但差异无统计学意义（P＞0.05）.干预Ⅰ组和干预Ⅱ组肾脏细胞增生、新月体的形成及免疫复合物的沉积均少于肾炎模型组,但干预Ⅰ组更为明显.对照Ⅰ组和对照Ⅱ组之间无明显变化.结论 早期应用抗GBM抗体的中和性单克隆抗体能够有效改善抗GBM肾炎大鼠的肾脏病变.Objective To observe the effect of neutralizing monoclonal antibodies to antiglomerular basement membrane （GBM） antibody on anti-GBM nephritis rats. Methods Wistar rats were randomly divided into five groups： control group Ⅰ was a negative control and was injected with healthy human IgG via the caudal vein. Control group Ⅱ was injected with neutralizing monoclonal antibodies to anti-GBM antibody only. Anti- GBM nephritis group was injected with human anti-GBM antibody via the caudal vein only. Intervention group Ⅰ was injected with human anti-GBM antibody via the caudal vein and then with neutralizing monoclonal antibodies to anti-GBM antibody at day 7. Intervention group Ⅱ was injected with human antiGBM antibody via the caudal vein and then with neutralizing monoclonal antibodies to anti-GBM antibody at day 14. The blood, urine and kidney tissue were collected at day 7, 14, 21 for analysis of 24-hour urinary protein, BUN, Ser and histological study. Results At day 21, there were significant decreases in intervention group Ⅰ compared with anti-GBM nephritis group in 24-hour proteinuria [（16.62±5.53） g], BUN[（11.53±2.26） mmol/L] and Scr [（102.46±16.86） μmol/L] （P〈0.05）, and also in intervention group Ⅱ as compared to anti-GBM nephritis group, but no significant difference was found （P〉0.05） . There was obvious decrease of renal cell proliferation,crescent formation and deposition of immune complexes in intervention group Ⅰ and intervention group Ⅱ compared with anti-GBM nephritis group, while such improvement in intervention group Ⅰ was more significant. There was no significant change in control group Ⅰ and control group Ⅱ.Conclusion The early application of neutralizing monoclonal antibodies to anti-GBM antibodies can effectively improve the kidney lesions of anti-GBM nephritis rats.

关 键 词：抗体 单克隆 抗肾小球基膜疾病 抗体 抗肾小球基膜 

分 类 号：R692.3[医药卫生—泌尿科学]