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MRL/lpr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/lpr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±0.16,0.32±0.09,0.44±0.18,1.95±0.19) U/ml、尿蛋白定量(24 h)水平降低(1.63 ±0.63,0.40±0.23,0.82±0.21,10.86±2.17) mg、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/lpr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,便于推广的新的多靶点免疫抑制剂治疗方案提供了实验依据.

abstractsObjective 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.