氟达拉宾对系统性红斑狼疮BXSB小鼠狼疮活动的影响

Influence of Fludarabine on lupus activity of BXSB mice

目的 :探讨氟达拉宾对系统性红斑狼疮BXSB小鼠狼疮活动的影响 ,氟达拉宾治疗重型系统性红斑狼疮的可能性、有效性及其可能的机制。方法 :用 30mg (m2 ·d) ,连续 3天氟达拉宾尾静脉注入BXSB小鼠体内 ,用血液分析仪分析用氟达拉宾前后不同时间小鼠外周血白细胞的变化 ,用ELISA方法测定BXSB小鼠血清抗ds DNA抗体、抗核抗体的变化 ,免疫荧光检查肾组织的病理改变 ,尿蛋白试纸检测用氟达拉宾前后BXSB小鼠的蛋白尿 ,流式细胞仪分析T淋巴细胞表面CD4 + Fas+ 、CD8+ Fas+ 、、CD4 5RO+ Fas+ 表达的变化。结果 :用氟达拉宾后BXSB小鼠外周血白细胞数从第 3天开始下降 ,至第 7天时白细胞下降至最低值〔(0 5± 0 2 )× 10 9L- 1 〕 ,白细胞上升至 1 0× 10 9L- 1 的时间是用药后 19天 ;BXSB小鼠血清抗ds DNA抗体、抗核抗体的水平明显下降 ,分别出现在用氟达拉宾后第 14、2 1天时 ;用药后第 2 8天氟达拉宾组 72 7%的BXSB小鼠肾组织进行免疫荧光病理检查 ,其荧光强度由 +～ ++→± ;用氟达拉宾后第 2 1、2 8天尿蛋白从 ++～ +++转±～ -占 81 8% ;用Flu后BXSB小鼠CD4 + Fas+ 、CD8+ Fas+ 、CD4 5RO+ Fas+ 的表达均明显低于用Flu前。结论 :氟达拉宾可明显减少BXSB小鼠血清抗ds DNA抗体、抗核抗体的水平 。

Objective:To investigate influence of Fludarabine to lupus activity of lupus mice and the effectiveness and safety of Fludarabine on the treatment of BXSB lupus mice and their possible methanism Methods:Fludarabine of 30 mg/(m 2·d) was injected into BXSB by tail vein,3 days continuously Results of treatment was observed through counting number of peripheral blood WBC Anti ds DNA and anti nuclear antibody in BXSB serum was measured by ELISA Pathologic transformation of kidney or urine protein was measured by immunofluorescence or urine protein test paper after treated by Fludarabine Expression of CD4 +Fas +?CD8 +Fas +?CD45RO + Fas + on T lymphocyte were measured by flowcytometry Results:The number of peripheral blood WBC of BXSB mice began to decline from the third day after treated by Fludarabine The lowest value 〔0 5±0 2)×10 9 L -1 〕of the number of peripheral blood WBC appeared on the seventh day and on the nineteenth day the number of peripheral blood WBC was up to 1 0×10 9 L -1 after treated by Fludarabine The falling of anti ds DNA and anti nuclear antibody in BXSB serum appeared on the fourteenth and twentieth one day after treated by Fludarabine, respectively Reduction of from +～++ turning±kindey immunofluorescence were 72 7% in group of Fludarabine Reduction of protein urine from ++～+++ turning ±～ - appeared on the twentieth one and twentieth eight days Reduction of expression of CD4 +Fas +?CD8 +Fas +?CD45RO + Fas + on T lymphocyte was obvious after treated by Fludarabine Conclusion:Fludarabine can evidently reduce the serum level of anti ds DNA and anti nuclear antibody of BXSB and reduce injury of kidney and formation of protein urine So Fludarabine may have good curative effect to severe SLE Fludarabine can reduce expression of CD4 +Fas +?CD8 +Fas +?CD45RO + Fas + on T lymphocyte,which may be one of methanism of Fludarabine to SLE