不同给药途径时抗核抗体独特型多肽对狼疮样肾炎小鼠作用的探讨

目的应用抗核抗体独特型多肽免疫治疗狼疮肾炎小鼠,观察其对狼疮肾炎模型小鼠肾脏的保护作用。方法将35只雌性GVHD狼疮样肾炎小鼠(C57BL/10×DBA/2)F1分为3组,肾炎模型对照组(10只),口服多肽实验组(10只),皮下注射多肽实验组(15只)。3组小鼠均于24周龄处死,观察3组小鼠体质量、尿蛋白、肾脏组织学及血清IL-6水平的变化。结果在给予多肽12周时,皮下注射组和口服多肽组小鼠肾脏损害较对照组明显减轻;血清IL-6水平也较对照组明显降低。在给予多肽10周时,皮下注射组小鼠体质量明显高于对照组小鼠,12周时口服组体质量也明显高于对照组。给予多肽4周时,皮下注射组小鼠尿蛋白明显少于对照组,8周时口服组尿蛋白也明显少于对照组。结论口服独特型多肽对GVHD狼疮样肾炎小鼠肾脏同样有保护作用。

The Protective Effect of Idiotypic Peptide on Kidney in the GVHD Lupus Nephritis Mice

Objective Previous studies showed that subcutaneous injection of anti-dsDNA antibody idiotypic peptide had the protective effect on autoimmune lupus nephritic mice.Recently,some studies have found that the idiotypic peptide immunization can induce the decrease of specific T cell proliferation and autoantibodies production in animal models.And this may lead us to find a new method to manage the lupus nephritis.The present study intends to explore this kind of protective effect through other route of idiotypic peptide intake.Methods In order to get the lupus nephritic animal model,we invite the GVHD(C57BL/10×DBA/2) F1 mice.For the induction of chronic graft-versus-host disease(GVHD),8-10-week-old(C57B1/10×DBA/2)F1 hybrids were used as recipients,and the donor lymphocytes were from DBA/2 mice.Single-cell suspensions containing a mixture of donor's thymus,spleen,and lymphonode cells were injected intravenously 4 times at 3 to 4 day intervals.The recipient mice develop a variety of pathologic alterations associated with the formation of autoantibodies.A SLE-like disease was evoked,as in human systemic lupus erythematosus,autoantibodies were directly against nuclear antigens.Corresponding to human lupus nephritis,antinuclear antibodies are thought to play a pathologic role in animal renal involvement.For this study,thirtyfive females(C57BL/10×DBA/2) F1 were used for study.Ten of them were in the oral group,fifteen were in the subcutaneous group,and others served as controls.All of them were killed at 24 weeks of age,and body weight,urinary protein,renal histology,and serum IL6 levels were observed.Results After 12 weeks of oral or subcutaneous idiotypic peptide intake,the renal damage was significantly diminished than that in the control mice,and serum IL-6 level were significantly lower.After 10 weeks of idiotypic peptide subcutaneous injection,and after 12 weeks' oral intake,the body weight was significantly higher than that of the control ones.The urinary protein was reduced in subcutanious injection group after 4 weeks treatment,and in oral intake group after 8 weeks' treatment than that in the control ones.Conclusion Oral intake of the anti-dsDNA antibody idiotypic peptide has the same protective effect on lupus nephritis in(C57BL/10×DBA/2) F1 mice as that in subcutaneous injection.