TACI融合蛋白对免疫球蛋白A肾病大鼠肾脏损害的影响

Effect of TACI fusion protein on renal damage in rats with immunoglobulin A nephropathy

目的探讨TACI融合蛋白(TACI-Ig)对免疫球蛋白A肾病(IgAN)大鼠肾脏损害的影响。方法将24只SD大鼠随机分为对照组、模型组、TACI-Ig组、药物对照组,每组6只。正常对照组、模型组给予生理盐水,TACI-Ig组给予TACI-Ig(14.36 mg/kg),药物对照组给予醋酸泼尼松(5 mg/kg)。比较各组24 h尿蛋白定量(24h-UP)、血清肌酐(Scr)、尿素氮(BUN)、低半乳糖基化IgA1(Gd-IgA1)、Toll样受体4(TLR4)、髓样分化因子88(MyD88)、核转录因子κB(NF-κB)蛋白及mRNA水平,并分析TACI-Ig对肾脏损害的影响。结果模型组24h-UP水平显著高于正常对照组,而TACI-Ig组、药物对照组24h-UP水平显著低于模型组,差异有统计学意义(P<0.05)。TACI-Ig组血清Scr水平低于模型组,差异有统计学意义(P<0.05)。TACI-Ig组、药物对照组肾组织系膜区沉积免疫复合体的增加受到明显抑制。模型组大鼠血清Gd-IgA1水平高于正常对照组,而低于TACI-Ig组,差异有统计学意义(P<0.01)。药物对照组血清Gd-IgA1水平低于模型组,而高于TACI-Ig组,差异有统计学意义(P<0.01)。TACI-Ig组TLR4、MyD88、NF-κB蛋白水平低于模型组,差异有统计学意义(P<0.05)。药物对照组TLR4、MyD88蛋白水平高于TACI-Ig组,差异有统计学意义(P<0.05)。TACI-Ig组TLR4、MyD88、NF-κB mRNA水平低于模型组,差异有统计学意义(P<0.05)。结论TACI-Ig对IgAN有较好的治疗作用,可改善IgAN大鼠肾功能,抑制肾小球系膜基质扩张和系膜细胞增殖。

Objective To investigate the effect of transmembrane activator and calcium modulator cyclophilin ligand interactor-immunoglobulin(TACI-Ig)on renal damage in rats with IgA nephropathy(IgAN).Methods A total of 24 SD rats were randomly divided into the normal control,the model,the TACI-Ig,and the drug control groups with six rats per group.The normal control and model groups received saline,the TACI-Ig group received TACI-Ig(14.36 mg/kg),and the drug control group received prednisolone acetate(5 mg/kg).Twenty-four-hour urinary protein(24h-UP),serum creatinine(Scr),blood urea nitrogen(BUN),galactose-deficient IgA1(Gd-IgA1),Toll-like receptor 4(TLR4),Myeloid differentiation factor 88(MyD88),Nuclear factor kappa B(NF-κB)protein and mRNA levels were compared among groups to analyze the influence of TACI-Ig on renal damage.Results The 24h-UP levels in the model group were significantly higher than those in the normal control group,while levels in the TACI-Ig and drug control groups were significantly lower than those in the model group(P<0.05).Serum CRE levels in the TACI-Ig group were lower than those in the model group(P<0.05).Deposition of immune complexes in the mesangial area of renal tissues was significantly inhibited in the TACI-Ig and drug control groups.Serum Gd-IgA1 levels in the model group were higher than those in the normal control group but lower than those in the TACI-Ig group(P<0.01).Serum Gd-IgA1 levels in the drug control group were lower than those in the model group but higher than those in the TACI-Ig group(P<0.01).TLR4,MyD88,and NF-κB protein levels in the TACI-Ig group were lower than those in the model group(P<0.05).TLR4,MyD88 protein levels in the drug control group were higher than those in the TACI-Ig group(P<0.05).TLR4,MyD88,and NF-κB mRNA levels in the TACI-Ig group were lower than those in the model group(P<0.05).Conclusion TACI-Ig exhibits therapeutic efficacy in IgAN,improving renal function in rats and inhibiting mesangial matrix expansion and mesangial cell proliferation.