地塞米松对MRL/lpr狼疮小鼠认知功能的保护作用

Effects of dexamethasone on MRL/lpr mice with systemic lupus erythematosus complicated with cognitive dysfunction

目的:探讨地塞米松对MRL/lpr狼疮小鼠认知功能的影响。方法:MRL/lpr狼疮小鼠随机分为MRL/lpr组、MRL/lpr+地塞米松(1.5 mg/kg)组,每组10只;野生型正常对照组C57BL/6小鼠10只。采用Morris水迷宫观察各组小鼠认知功能和行为。检测各组小鼠血清、海马组织中炎症因子白细胞介素-6(interleukin-6,IL-6)、白细胞介素-1β(interleukin-1β,IL-1β)、肿瘤坏死因子-α(tumor necrosis factor,TNF-α)含量;检测各组小鼠海马组织中磷脂酰肌醇3-激酶(phosphatidylinositol 3-kinase,PI3K)/蛋白激酶B(protein kinase B,AKT)/核因子-κB p65(nuclear factor-kappabinding p65,NF-κB p65)相关蛋白P-PI3K,P-Akt和磷酸化核转录因子κB抑制蛋白a(phospho-inhibitor of nuclear factor kappa Ba,P-IκBa)及P-NF-κB p65的表达。免疫组织化学法观察各组小鼠海马区P-NF-κB p65阳性表达。结果:地塞米松能缓解MRL/lpr狼疮小鼠认知功能障碍,降低血清及海马组织IL-6,IL-1β,TNF-α的表达;抑制P-PI3K,P-Akt,P-IκBa和P-NF-κB p65的表达。结论:地塞米松可能通过降低MRL/lpr狼疮小鼠海马区TNF-α和IL-1β水平,从而对其认知功能起保护作用。

Objective：To evaluate the effects of dexamethasone on systemic lupus erythematosus complicated with cognitive dysfunction.Methods：Ten wild type mice and 20 MRL/lpr mice were applied for the research.MRL/lpr mice were randomly assigned to a MRL/lpr group and a MRL/lpr＋dexamethasone（1.5 mg/kg）group.Interleukin-6（IL-6）,IL-1β,and tumor necrosis factor alpha（TNF-α）in serum and hippocampus were detected.The protein phosphorylation levels of phosphoinositide 3-kinase（P-PI3K）,protein kinase B（P-Akt）,NF-kappa-B inhibitor alpha（P-IκBa）and nuclear transcription factor kappa-B p65（P-NF-κB p65）were detected by Western blot,the level of P-NF-κB p65 also was detected by immunohistochemistry.Results：Treatment with dexamethasone（1.5 mg/kg）alleviated the cognitive dysfunction and decreased the levels of IL-6,IL-1β and TNF-αin serum and hippocampus,and reduced the levels of P-PI3K,P-Akt,P-IκBa and P-NF-κB p65 in hippocampus in MRL/lpr mice.Conclusion：Dexamethasone may play a protective role in the cognitive function by decreasing the levels of TNF-αand IL-1βin the hippocampus of MRL/lpr lupus mice.