慢性移植物抗宿主病狼疮样小鼠肾组织集落刺激因子-1表达及泼尼松的调控作用

Inhibition of prednisone on overexpression of colony stimulating factor-1 in renal tissue of murine chronic graft-versus-host disease lupus nephritis

目的 观察集落刺激因子 1(CSF 1)在慢性移植物抗宿主病 (GvHD)狼疮样小鼠肾组织中的表达及泼尼松的调控作用。方法 GvHD狼疮样小鼠模型参照有关文献建立。按随机设计原则将模型动物分两组即模型组 (A组 )和泼尼松治疗组 (B组 ) ,另设正常对照组 (C组 ) ,每组均有 8只动物。CSF 1蛋白检测采用免疫组织化学方法 ,mRNA表达采用原位杂交技术检测。结果 ①A组肾组织中CSF 1蛋白表达显著高于C组 (P <0 0 5 ) ,肾小球、肾小管 间质中均有表达 ,尤以肾小管 间质表达更为丰富 ,而B组CSF 1在肾小球、肾小管 间质表达均显著减少 (P <0 0 5 )。②A组肾组织中CSF 1mRNA表达显著高于C组 (P <0 0 5 ) ,经泼尼松治疗后CSF 1mRNA受到明显抑制。③A组中CSF 1蛋白和mRNA表达呈正相关关系 (r =0 6 15 ,P <0 0 5 ) ,A组肾组织中CSF 1蛋白表达和 2 4h尿蛋白排泄呈正相关 (r =0 5 78,P <0 0 5 )。结论 慢性GvHD狼疮样小鼠肾组织特别在肾小管 间质中CSF 1蛋白和mRNA表达均显著增高 ,泼尼松在改善肾组织病理改变的同时 ,对CSF 1表达亦起抑制作用 ,提示CSF 1参与狼疮肾炎的发生和发展 ,泼尼松抑制CSF 1过度表达可能是其在狼疮肾炎中发挥治疗作用的机制之一。

Objective To detect the expression of colony stimulating factor (CSF) 1 in kidney tissue of murine chronic graft versus host disease (GvHD) lupus nephritis,and to investigate the inhibition of prednisone on CSF 1 Methods The protein and mRNA expression of CSF 1 were detected by immunohistochemistry and in situ hybridization,respectively.Results The protein and mRNA expression of CSF 1 were significantly increased in kidney tissue of GvHD mice,respectively,which could be detected in glomerular,tubular and interstitial cells,especially much in tubular epithelial cells and interstitial mononuclear cells.The protein expression of CSF 1 in kidney tissue was correlated positively with its mRNA expression ( r =0 615, P <0 05) and urinary protein excretion ( r =0 578, P <0 05).Prednisone treatment significantly prevented the increase of urinary protein excretion,anti dsDNA antibody,glomerular cell proliferation,and interstitial cell infiltration in the lupus mice,indicating the beneficial effects of prednisone on this lupus nephritis.Prednisone also significantly suppressed the increased renal CSF 1 expression (protein and mRAN).Conclusion This study provides the evidence of the marked increase in renal CSF 1 expression in murine GvHD lupus nephritis,especially in tubules and interstitial cell.The beneficial effect of prednisone on this lupus nephritis may be partially mediated by the suppression of CSF 1