Pi3-k/Akt信号通路在狼疮样小鼠肾组织中的激活及霉酚酸酯的调控作用

Inhibition of mycophenolate mofetil on activation of Pi3-k/Akt pathway in renal tissue of murine chronic graft-versus-host disease lupus nephritis

目的:研究Pi3-k/Akt信号通路在狼疮样小鼠肾组织中的激活及霉酚酸酯(MMF)的调控作用。方法:建立cGVHD狼疮样小鼠模型。随机分为3组,每组6只小鼠,将模型动物分两组即模型组和MMF治疗组,另设对照组。检测各组血肌酐、尿素氮及尿蛋白变化,观察肾组织纤维化程度,检测各组小鼠肾组织中P-Akt及Akt蛋白表达情况。结果:12周模型组的小鼠肾小球系膜节段、弥漫性增生,且血肌酐、尿素氮及尿蛋白较对照组均明显增加。Western blotting结果证实模型组肾组织中Akt及P-Akt蛋白表达与正常组相比均明显增加(P<0.01),而MMF治疗组与模型组相比其Akt及P-Akt的蛋白表达均降低,且血肌酐、尿素氮及尿蛋白水平也受到抑制。结论:Pi3-k/Akt信号通路参与了狼疮肾炎的发病,MMF抑制Akt的磷酸化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 activation of Pi3-k/Akt pathway in renal tissue of murine chronic graft-versus-host disease（cGVHD） lupus nephritis,and to investigate the inhibition of mycophenolate mofetil（MMF） on activation of Pi3-k/Akt pathway.Methods： Mice models of cGVHD lupus nephritis were established.Mice were randomly divided into three groups,namely the control group,the model group,and the MMF treated group.Histopathology,renal function and proteinuria were observed.The protein levels of Akt and P-Akt in renal tissue were detected by Western blotting.Results： Western blotting results showed that the protein levels of Akt and P-Akt were significantly increased in renal tissue of cGVHD mice,and the level of BUN and Ccr in serum and proteinuria were also higher than in the control group.MMF ameliorated the histological lesions,maintained normal renal function,normalized proteinuria and suppressed Akt and P-Akt expression.Conclusion： This study suggests that the Pi3-k/Akt pathway is activated in renal tissue of murine cGVHD lupus nephritis.The beneficial effect of MMF on lupus nephritis may be partially mediated by the inhibition of Pi3-k/Akt pathway.