慢性移植物抗宿主病狼疮样小鼠肾组织RANTES表达及泼尼松的调控作用

Prednisone modulation on overexpression of RANTES in renal tissue of murine chronic graft-versus-host disease lupus nephritis

目的 观察趋化因子RANTES (“regulateduponactivationnormalTcellexpressedandsecreted”)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。RANTES的蛋白表达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 ①模型组 (A组 )肾组织中RANTES蛋白表达显著高于正常对照组 (C组 ) (P <0 0 5 ) ,肾小球和肾小管间质中均有表达 ,尤以肾小管 间质表达更为丰富 ;而泼尼松治疗组 (B组 )RANTES在肾小球和肾小管 间质表达均显著减少 (P <0 0 5 )。②A组肾组织中RANTESmRNA表达显著高于C组 (P <0 0 5 ) ,经泼尼松治疗后RANTESmRNA受到明显抑制。③A组中RANTES蛋白和mRNA表达呈正相关 (r =0 6 12 ,P <0 0 5 )。结论 慢性GVHD狼疮样小鼠肾组织中RANTES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RANTES表达亦起抑制作用 ,提示RANTES可能参与了狼疮肾炎的发病机制 ,泼尼松抑制RANTES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 'regulated upon activation normal T cell expressed and secreted' (RANTES) in kidney tissue of murine chronic graft versus host disease (GVHD) lupus nephritis,and investigate the prednisone modulation on RANTES.Methods The protein and mRNA expressions of RANTES were detected by immunohistochemistry and in situ hybridization,respectively.Results The protein and mRNA expressions of RANTES were significantly increased in kidney tissue of GVHD mice,respectively,which could be dectected in glomerular,tubular and interstitial cells,especially much in tubular epithelial cells and interstitial mononuclear cells.The protein expression of RANTES in kidney tissue was correlated positively with its mRNA expression ( r =0 612, P <0 05).Prednisone treatment significantly prevented the increase in 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 significantly suppressed the increased renal RANTES expression (protein and mRNA).Conclusion The results provide the evidence of the marked increase in renal RANTES expression in murine GVHD lupus nephritis.The beneficial effect of prednisone on this lupus nephritis may be partially mediated by the suppression of RANTES.