硫唑嘌呤与霉酚酸酯联合应用对儿童狼疮肾炎的长期免疫抑制作用研究

Long-term immunosuppressive effect of azathioprine combined with mycophenolate mofetil on children with lupus nephritis

为探索硫唑嘌呤(azathioprine,AZA)与霉酚酸酯(mycophenolate mofetil,MMF)联合应用对狼疮肾炎(lupus nephritis,LN)儿童免疫系统的长期影响,选择四川省人民医院2014年3月至2016年8月收治的LN患儿93例,采用随机数字表法分为联合治疗组(n=47)与MMF组(n=46)。其中MMF组患儿在基础治疗基础上给予吗替麦考酚酯胶囊口服,联合治疗组患儿在MMF组基础上给予AZA片剂口服。检测两组患儿治疗前、治疗6个月后与治疗后2年BUN、Scr、胱抑素C(cystatin-C,CysC)、补体C3、血清钙结合蛋白复合物(S100A8/A9)、CXC型趋化因子配体16(CXC ligand 16,CXCL16)与巨噬细胞迁移抑制因子(macrophage migration inhibitory factor,MIF)水平;检测24h尿蛋白定量(24-hour urinary protein quantification,24hU-Pr)与尿MIF水平;统计治疗过程中两组患儿不良反应发生情况。结果显示,治疗前两组患儿各检测指标差异无统计学意义(P>0.05);治疗结束与治疗后2年两组患儿BUN、24hU-Pr、Scr水平较本组治疗前明显降低,且联合治疗组明显低于MMF组(P<0.05);两组患儿补体C3水平较本组治疗前明显升高,且联合治疗组明显高于MMF组(P<0.05);两组患儿S100A8/A9、CXCL16与CysC水平较本组治疗前明显降低,且联合治疗组明显低于MMF组(P<0.05);两组患儿血清MIF与尿MIF水平较本组治疗前明显降低,且联合治疗组明显低于MMF组(P<0.05);两组患儿总不良反应发生率差异无统计学意义(P>0.05)。由此,AZA与MMF联合治疗可有效改善LN患儿肾功能,对自身免疫反应具有明显、长期的抑制作用,且安全性较高,具有较大的临床推广意义。

To investigate the long-term immunosuppressive effect of azathioprine(AZA)combined with mycophenolate mofetil(MMF)on children with lupus nephritis(LN),93LN children admitted to Sichuan Provincial People's Hospital from March 2014to August 2016were selected and divided into the combined treatment group(n=47)and the MMF group(n=46)by random number table method.MMF group received the oral MMF capsules combined with basic treatment,and the combined treatment group were given additional oral AZA tablets.The blood serum urea nitrogen(BUN),serum creatinine(Scr),serum cystatin-C(CysC),C3complement,serum calcium binding protein complex(S100A8/A9),serum CXCL16,serum macrophage migration inhibitory factor(MIF)levels,24-hour urinary protein quantification(24hU-Pr),urinary MIF levels and adverse reactions were measured at given time points.The results showed that,before treatment,there were no differences between the two groups in levels of all items.At the end of treatment and two years thereafter,levels of BUN,24hU-Pr and Scr were decreased in both groups,with the combined therapy group more dramatically(P<0.05).With respect to other indexes,the levels of C3in the combined treatment group were significantly higher than those in the MMF group(P<0.05)after the treatment.The levels of S100A8/A9,CXCL16and CysC,serum MIF and urinary MIF were significantly lower than before treatment,and these in the combined treatment group were significantly lower than those in the MMF group(P<0.05).The incidence of total adverse reactions manifested no differences between the two groups(P>0.05).Taken together,the combined application of AZA and MMF can improve the renal function effectively and safely,and has the clinical significance with obvious and long-term inhibitory effect on autoimmunity of children with LN.