半量免疫抑制剂多靶点治疗狼疮肾炎的实验研究

【摘要】目的探讨半量泼尼松、环磷酰胺与来氟米特联合多靶点免疫抑制治疗MRIJ!pr小鼠LN的疗效及安全性，为临床寻找安全、有效、价廉的治疗LN方案提供实验依据。方法10周龄雌性MRL／lDr狼疮小鼠28只，采用随机数字表法分成4组，每组7只，A组：空白对照组，B组：经典对照组，C组：全量联合对照组，D组：半量联合治疗组。治疗12周后进行疗效及安全性评价。采用单因素方差分析、q检验、Pearson相关分析进行统计学处理。结果治疗12周后，B组、C组、D组与A组比较，抗dsDNA抗体滴度（0．43±O．16，0．32±0．09，0．44±0．18，1．95±0．19）U／ml、尿蛋白定量（24h）水平降低（1．63±0．63，0．40±0．23，0．82±0．21，10．86±2．17）m卧血肌酐水平（71±8，60±5，68±3，121±10）μmol／L及生存率差异均有统计学意义（P〈0．05），B组、C组、D组肾组织病理损害均较A组减轻。B组、C组、D组的疗效相当，不良反应D组最轻，C组最重。结论泼尼松、环磷酰胺与来氟米特半量多靶点免疫抑制联合治疗MRL／Ipr小鼠LN与经典组、全量组相比，疗效相当，不良反应减轻。本研究为临床探索价廉、安全、有效，便于推，“的新的多靶点免疫抑制剂治疗方案提供了实验依据。

Objective To investigate the efficacy and adverse reactions of half-dose glucocorticosteroid and cytoxan,combined with leflunomide for the treatment of lupus nephritis (LN) of MRL/lpr mice,and provide experimental evidences for LN therapy.Methods Twenty-eight 10-week-old MRL/lpr mice were randomly divided into four groups:Group A,blank control group; Group B,classical control group; Group C,full-dose control group; Group D,half-dose treatment group,with 7 mice in each group.The therapeutic efficacy and side reactions in the four groups were observed and compared before and 12 weeks after treatment.Statistical analysis was conducted with one-way ANOVA,q test and Pearson's correlation analysis.Results The serum anti-double stranded DNA (anti-dsDNA) antibody titers (0.43±0.16,0.32±0.09,0.44± 0.18,1.95±0.19) U/ml,serum creatinine level (1.63±0.63,0.40±0.23,0.82±0.21,10.86±2.17) mg,24-hour urine protein excretion level (71±8,60±5,68±3,121±10) μmol/L and renal pathological changes in group B,C,D were significantly improved than those of the group A (P＜0.05) after 12 weeks treatment.There was no significant difference in the efficacy between group B,C,and D (P＞0.05).The incidence of adverse reactions in group D was significantly lower than that in other groups (P＜0.05).Conclusion Multi-target therapy,such as half-dose prednisone and CTX,combined with leflunomide can effectively control lupus disease activity with less side effects.This regimen is cheap,safe and effective for the treatment of LN in MRUL/lpr mice.This study has provided animal evidences for this multi-target therapy for LN.