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目的研究TACI融合蛋白(TACI-Ig)对系统性红斑狼疮转基因小鼠(MRL/lpr)的治疗作用及部分机制。方法将MRL/lpr小鼠随机分为6组:模型组、TACI-Ig(3.75、7.5、15 mg/kg)治疗组、阳性对照药强的松组、阴性对照药Ig-Fc组,另选BALB/c小鼠作为正常对照组,除强的松组每日灌胃给药外,其余各组隔日皮下注射给药,共计8周,模型组和正常组给予生理盐水。HE染色法检查动物的脾脏和淋巴结病理改变,计算动物的脾脏和胸腺指数,3H-TdR掺入法检测刀豆素A(ConA)和脂多糖(LPS)诱导的T和B淋巴细胞增殖反应,ELISA法检测小鼠血清中免疫球蛋白(IgG1、IgG2a)、抗核抗体(ANA)、抗双链DNA抗体(anti-dsDNA)水平,流式细胞术检测肠系膜淋巴结T淋巴细胞和脾脏B淋巴细胞亚群。结果 TACI-Ig(7.5、15 mg/kg)皮下注射给药能显著改善模型小鼠脾脏和淋巴结增生等病理变化;降低小鼠升高的脾脏指数,降低LPS诱导的脾淋巴细胞的增殖反应;显著降低模型小鼠血清中升高的IgG1、ANA和anti-dsDNA水平;能有效降低脾脏总B淋巴细胞(CD19+)、成熟B淋巴细胞(CD19+IgD+)、早期B淋巴细胞(CD19+IgM+)数量,TACI-Ig给药可升高MRL/lpr小鼠活化Th淋巴细胞(CD4+CD25+)数量,降低表达活化诱导分子Th淋巴细胞(CD4+CD69+)的表达,而对记忆B淋巴细胞(CD19+CD27+)和其它T淋巴细胞亚群活性无明显影响。结论 TACI-Ig皮下注射给药对MRL/lpr小鼠具有治疗作用,其机制可能与调节T、B淋巴细胞功能有关。
Objective To investigate the therapeutic effect and mechanism of TACI-Ig on the systemic lupus erythematosus transgenic mice (MRL / lpr). Methods MRL / lpr mice were randomly divided into 6 groups: model group, TACI-Ig (3.75,7.5,15 mg / kg) treatment group, positive control group prednisone group and negative control drug Ig-Fc group, BALB / c mice as normal control group, except for prednisone group were given intragastrically every other day, the other groups were subcutaneously injected on the next day for a total of 8 weeks. The model group and the normal group were given normal saline. The pathological changes of the spleen and lymph nodes were examined by HE staining. The spleen and thymus index were calculated. The proliferation of T and B lymphocytes induced by ConA and LPS were detected by 3H-TdR incorporation assay. Serum immunoglobulin (IgG1, IgG2a), anti-nuclear antibody (ANA) and anti-dsDNA level were detected by ELISA. The levels of mesenteric lymph node T lymphocytes and spleen B lymphocytes were detected by flow cytometry Subgroups. Results Subcutaneous injection of TACI-Ig (7.5, 15 mg / kg) could significantly improve the pathological changes of the spleen and lymph node in model mice, decrease the spleen index and decrease the proliferative response induced by LPS in spleen lymphocytes. Significantly decreased the levels of IgG1, ANA and anti-dsDNA in the serum of model mice; decreased the levels of total B lymphocytes (CD19 +), mature B lymphocytes (CD19 + IgD +), and early B lymphocytes (CD19 + IgM + TACI-Ig administration could increase the number of activated Th lymphocytes (CD4 + CD25 +) in MRL / lpr mice and decrease the expression of activation-inducing molecules Thymocytes (CD4 + CD69 +), but not in memory B lymphocytes + CD27 +) and other T lymphocyte subsets activity had no significant effect. Conclusion The subcutaneous injection of TACI-Ig has a therapeutic effect on MRL / lpr mice. The mechanism may be related to the regulation of T and B lymphocyte function.