蛋白激酶B通路在系统性红斑狼疮患者外周血单个核细胞凋亡中的作用及其调控机制  

Akt pathway and its regulatory mechanism in the peripheral blood mononuclear cells in patients with systemic lupus erythematosus

作　　者：陈东育[1] 李芳[1] 朱广婷[1] 

机构地区：[1]山东省泰安市中心医院风湿免疫科,271000

出　　处：《中华风湿病学杂志》2016年第6期368-371,共4页Chinese Journal of Rheumatology

基　　金：山东省自然科学基金（ZR2014HL08）;山东省医药卫生科技发展计划（2015WS0116）;山东省泰安市科技发展计划（20123065,20132103）

摘　　要：目的探讨蛋白激酶B（Akt）在SLE患者PBMCs中的表达及其对下游分子叉头转录因子O亚族（FOXO1）、Bim等的调控，明确Akt/FOXO1/Bim信号通路在SLE患者PBMCs凋亡中的作用。方法选择SLE活动患者、SLE缓解患者和健康对照，应用蛋白印迹法检测各组PBMCs中Akt、FOXO1及Bim蛋白的表达水平，应用流式细胞仪检测各组PBMCs的凋亡。采用t检验进行统计学分析。结果SLE活动患者PBMCs凋亡率（16.3±4.0）%明显高于SLE缓解患者（5.6±2.9）%和健康对照（5.2±4.2）%（t值分别为4.83和5.05，P〈0.05），SLE活动组患者磷酸化Akt、磷酸化FOXO1及磷酸化Bim的蛋白表达水平均低于SLE缓解组和对照组（P〈0.05）。而PBMCs凋亡率以及上述各因子在SLE缓解组和对照组间差异无统计学意义。结论① Akt与SLE疾病的活动性有关，其活性降低可能促进SLE的发生和发展。② Akt的活性下降可能导致SLE患者PBMCs的凋亡增加，在这个过程中，Akt可能通过调节其下游的FOXO1和Bim的磷酸化水平，增强它们的促凋亡能力来发挥作用。Objective To explore the expression of Akt in peripheral blood mononuclear cells （PBMCs） and its regulatory role on its downstream molecules forkhead box transcription factor O1 （FOXO1） and Bim in patients with systemic lupus erythematosus （SLE）. The role of Akt/FOXO1/Bim signaling pathway on PBMCs apoptosis was clarified. Methods Sixty-three SLE patients and 23 healthy controls were enrolled. PBMC were separated from the peripheral blood specimen. Western blot technique was applied to analyze the expression of Akt, FOXO1 and Bim. Flow cytometry was applied to analyze PBMCs apoptosis. The t-test was used for statistical analysis.Results The apoptosis of PBMCs in patients with active SLE [（16.3±4.0）%] was significantly higher than that of patients with inactive SLE [（5.6±2.9）%] and normal controls [（5.2±4.2）%, t=4.83, 5.05; P〈0.05]. The levels of phosphorylation of Akt, FOXO1 and Bim expression was significantly decreased in patients with active SLE as compared with controls and patients with inactive SLE（P〈0.05）. However, these indicators had no significant difference between the controls and patients with inactive SLE （P〉0.05）.Conclusion ① The results of this studysuggest that the expression level of Akt may be a good indicator for disease activity of SLE. Decrease of Akt may promote the occurrence and development of SLE. ② Akt activity decline may lead to increased apoptosis of PBMCs. In this process, Akt may regulate its downstream FOXO1 and Bim phosphorylation levels which can enhance their ability to pro-apoptotic.

关 键 词：红斑狼疮 系统性 蛋白激酶B 外周血单个核细胞 细胞凋亡 

分 类 号：R593.241[医药卫生—内科学]