静脉应用核小体H2B表位肽防治小鼠实验性系统性红斑狼疮的研究

目的 探讨静脉途径应用基于核小体的表位肽防治系统性红斑狼疮(SLE)的可行性。方法 以凋亡细胞诱导的SLE样症状小鼠为模型，用核小体表位肽H2B14-28静脉途径诱导小鼠免疫耐受，观察实验小鼠自身抗体产生情况以及SLE样临床症状改善情况。结果用表位肽H2B14-28诱导免疫耐受以后，可显著降低实验小鼠抗核抗体(ANA)、抗双链DNA(dsDNA)抗体、抗RNP抗体和抗心磷脂(ACL)抗体的产生，同时显著改善小鼠蛋白尿、白细胞低下、肾脏免疫复合物沉积程度和病理损伤程度。结论 静脉途径应用核小体表位肽H2B14-28可有效阻止实验性SLE病变的形成，基于核小体表位肽的肽疫苗的研究有可能为SLE的防治开辟一条全新的思路和途径。

Prevention and treatment of experimental mice systemic lupus erythematosus by peptide with nucleosome H2B epitopes

Objective To investigate the effects of immune tolerance induced by peptide based on nucleosome H2B epitopes in prevention and treatment of systemic lupus erythematosus (SLE). Methods Based on a model of experimental systemic lupus erythematosus induced with syngeneic apoptotic lymphocytes to BALB/c mice, immune tolerance was induced by H2B14~28, administration intravenously with H2B Th cell epitope peptide. The effects of prevention and treatment were evaluated by changes in autoantibodies and SLE-like clinical manifestations. Results The peptide of H2B14~28 was highly effective in preventing autoantibody production of SLE (such as ANA, anti-dsDNA Abs, anti-RNP Abs and ACL Abs), and ameliorating clinical manifestations. Conclusion Tolerance to nucleosome induced by H2B14~28 peptide can significantly inhibit autoantibodies production and down-regulate clinical manifestations of SLE. So it may be a new way to treat and prevent SLE by nucleosome-based immune tolerance vaccine.