中国药理学通报2011，Vol.27Issue(4)：487-492,6.DOI:10.3969/j.issn.1001-1978.2011.04.011
TACI-Ig对MRL/lpr小鼠的治疗作用及其对小鼠肾组织JAK1-STAT1信号通路的影响
Effects of TACI-Ig on MRL/lpr mice and activation of JAK1-STAT1 signaling pathway in lupus nephritis
摘要
Abstract
Aim To study the effect of TACI-Ig on MRL/1pr mice and activation of JAK1 -STAT1 signaling pathway in lupus nephritis. Methods MRL/lpr mice were randomly divided into 6 groups, mice in group 1 were given normal saline as model group , mice in the other five groups were given TACI-Ig ( 3. 75 , 7. 5 , 15 mg' kg"), IgG-Fc (7.5 mg· kg-1, negative control) , prednisone (5 mg· kg-1, positive control) respectively , continuously for 8 weeks. Normal control ( BALB/c) group was given normal saline, and all groups were treated subcutaneously once every other day except prednisone group ( intragastrically once a day) . The general signs and damage index of MRL/1pr mice were observed after TACI-Ig treatment. Proteinuria of mice was detected by the demi-quantitate albustix . The sections of kidney tissues for pathological analysis were stained with HE. The serum levels of BUN, Cre and BLyS , IL-1O, IFN-γ were determined by automatic biochemistry analyzer and ELISA kits , respectively. The expression of phosphorylated JAK1 and STAT1 in renal tissue was detected by immunohistochemical techniques. Results TACI-Ig (7.5, 15 mg · kg-1 ) could significantly reduce the levels of proteinuria and damage index after 8 weeks. Mesangial cell hyperplasia, glomerular fibrosis and inflammatory cell infiltration were alleviated effectively. The serum levels of BUN , Cre, BLyS, IL-1O and IFN -γ were remarkably decreased too. Moreover, immunohistochemical results showed the protein expression of phospho -rylated JAK1 and STAT1 in renal tissue was obviously increased in model mice , especially in glomerular and renal interstitium , while it decreased significantly by TACI-Ig administration. Conclusions TACI-Ig has a beneficial effect on murine SLE by improving the clini -cal manifestations and renal pathological features of MRL/1pr mice, decreasing the levels of cytokines in serum and phosphorylation of JAK1 and STAT1 in renal tissue, which might be one of the mechanisms of TACI-Ig treatment for lupus nephritis .关键词
TACI-Ig/B淋巴细胞刺激因子/MRL/lpr小鼠/狼疮性肾炎/JAK1-STAT1/治疗分类
医药卫生引用本文复制引用
王杰,魏伟,严尚学,张小丹,王晶晶,吴成义,王文祥,黄敏,房健民,徐星铭..TACI-Ig对MRL/lpr小鼠的治疗作用及其对小鼠肾组织JAK1-STAT1信号通路的影响[J].中国药理学通报,2011,27(4):487-492,6.基金项目
国家自然科学基金资助项目(No 30973543) （No 30973543）
