P-糖蛋白单克隆抗体改善MRL/lpr狼疮鼠肾脏病变的研究

P-glycoprotein monoclonal antibody improves lupus-like syndrome in MRL/lpr mice

目的 探讨P-糖蛋白（P-glyeoprotein,P-gp）单克隆抗体（UIC2）在改善MRL/lpr狼疮鼠肾脏病变中的作用.方法 24只14周龄雌性MRl/lpr狼疮鼠分为3组：P-gp单克隆抗体1次治疗组（G1）、P-gp单克隆抗体3次治疗组（G2）、对照组（G0）.观察体重;采用考马斯亮蓝法检测24 h尿蛋白定量;采用酶联免疫吸附法试验（enzyme linked immunosorbent assay,ELISA）检测抗双链DNA（dsDNA）抗体水平;采用酶法检测血清肌酐水平;采用苏木素-伊红染色、免疫荧光和电镜观察肾脏病理改变.结果 ①22周时G1组和G2组体重高于G0组（P〈0.05）.② 24 h尿蛋白定量22周时Gl组[（1.9±1.1）mg]和G2组[（1.4±0.9）mg]低于G0组[（3.1±1.9）mg]（P〈0.05）;26周时G1组[（2.4±1.4）mg]和G2组[（1.8±1.1）mg]低于G0组[（5.3±2.2）mg]（P〈0.05）.③26周时血清肌酐G1组[（7.0±2.9）μmol/L]和G2组[（6.1±2.5）μmol/L]低于G0组[（12.7±1.3）umol/L]（P〈0.05）.④19周时,抗dsDNA抗体滴度G1组[（43±19）×10^2 U/mL]和G2组[（45±32）×10^2 U/mL]低于G0组[（87±39）×10^2 U/mL]（P〈0.05）;26周时G2组[（35±11）×10^2 U/mL]低于G0组[（59±35）×10^2 U/mL].⑤肾小球新月体形成率G1组（0.11±0.05）和G2组（0.09土0.01）低于G0组（0.23±0.07）,G2组较Gl组减低（P均〈0.05）.结论 P-gp单克隆抗体可改善MRl/lpr狼疮鼠肾脏病变的进展,减少尿蛋白、降低血清肌酐,对狼疮肾炎有显著疗效.

Objective To investigate the efficacy of P-glycoprotein monoclonal antibody in the treatment of MRL/lpr mice.Methods Twenty four 14-week-old MRL/lpr female mice were divided into 3 groups：Group 1（G1）were treated with P-glycoprotein monoclonal through caudal vein.Group 2（G2）were treated with P-glycoprotein monoclonal three times.Group 0 （G0）were treated with 0.5 mL normal saline as controls.24 hours proteinuria and body weight were assessed every two weeks.Enzyme linked immunosorbent assay （ELISA）was used to measure the levels of serum anti-dsDNA antibodies.Enzymatic method was used to detect the level of serum creatinine.The histopathology changes of the kidneys were observed.Results ①From the 22 th week,the body weight of Gl and G2 increased significantly than that of G0（P〈0.05）.②At the 22th week,24 hours proteinuria in Gl（1.9±1.1）mg and G2（1.4±0.9）mg was decreased than that in G0（3.1±1.9）mg（P〈0.05）.At the 26th week,24 hours proteinuria in G1（2.4±1.4）mg and G2（1.8±1.1）mg was also significantly decreased than that in G0（5.3±2.2）mg（P〈0.05）.③At week 26,serum creatinine decreased significantly in both G1（7.0±2.9）mol/L and G2（6.1±2.5）mol/L compared with that in G0（12.7±1.3）mol/L（P〈0.05）.④One week after treatment,the levels of anti-dsDNA antibodies in Gl（43±19）×10^2 U/mL and G2（45±32）×10^2 U/mL were both significantly decreased compared with those of G0（87±39）×10^2 U/mL（P〈0.05）.At the 26th week the difference between G2（35±11）×10^2 U/mL and G0（59±35）×10^2 U/mL was statistically significant.⑤The nephron crescent formation in G1（0.11±0.05）and G2（0.09±0.01）was significandy lower than that in G0（0.23±0.07）（P〈0.05）.The nephron crescent formation in G2 was significantly less than that in Gl（P〈0.05）.Conclusions P-glycoprotein monoclonal antibody is very effective for the treatment of MRL/lpr mice.It can reduce urinary protein and creatinine.