慢性移植物抗宿主病狼疮小鼠肾组织Akt信号通路蛋白表达及泼尼松的调控作用

目的:研究慢性移植物抗宿主病(GvHD)狼疮小鼠肾组织Akt信号通路蛋白在体内是否存在异常活化及泼尼松对Akt信号通路蛋白活化的调控作用。方法:肾组织Akt和磷酸化IκBα蛋白检测采用Western blot方法, NF-κB活性检测采用电泳迁移率改变实验(EMSA)。结果:注射单细胞悬液后第8周和第1２周, 狼疮鼠肾组织Akt活性、磷酸化IκBα及NF-κB活性均显著高于正常对照组(Ｐ＜0.05), 第16周, 狼疮鼠肾组织Akt活性、磷酸化IκBα及NF-κB活性均与正常对照组无显著差别(Ｐ＞0.05);第8周和第1２周时, 狼疮小鼠肾组织Akt活性与NF-κB活性均呈正相关 (分别为r=0.523和r=0.574, Ｐ＜0.05)。 泼尼松对狼疮小鼠外周血抗dsDNA抗体滴度和尿蛋白具有显著的抑制作用, 对肾脏病理改变有显著的改善作用, 同时, 泼尼松亦显著抑制狼疮小鼠肾组织Akt活性、磷酸化IκBα和NF-κB活性。结论：GvHD狼疮小鼠肾组织存在Akt-NF-κB信号通路异常活化, 泼尼松对该模型具有治疗作用可能与其抑制体内Akt-NF-κB信号通路异常活化有关。

Activation of Akt signal pathway cascades in kidney tissue in murine chronic graft-versus-host disease lupus nephritis and its regulation by prednisone

AIM:To examine whether Akt signal pathway proteins, including Akt, NF-κB and IκBα, are activated in kidney tissue of murine chronic graft-versus-host disease (GvHD) lupus nephritis in vivo, and whether prednisone suppresses activation of them.METHODS:Akt activity and phosphorylated IκBα were detected by Western-blot. Activation of NF-κB was detected by electropheretic mobility shift assay (EMSA). RESULTS:Activity of Akt, NF-κB and phosphorylated IκBα were significantly increased in kidney tissue of murine chronic graft-versus-host disease (GvHD) in 8th week and 12th week after monocell injection, respectively. However, they were no significant elevation in 16th week, when compared with controls. Prednisone treatment significantly prevented the increase in serum anti-dsDNA antibody level, urinary protein excretion and glomerular cell proliferation in GvHD mice, indicating the beneficial effects of prednisone on this model. Prednisone also significantly suppressed the increase in the activities of glomerular Akt, NF-κB and phosphorylated IκBα. CONCLUSION:This study provides the first evidence of marked increase in glomerular Akt-NF-κB signal pathway activities in murine chronic graft-versus-host disease lupus nephritis. The beneficial effect of prednisone on this lupus nephritis model may be partially mediated by the suppression of abnormal Akt- NF-κB activation.