SOCS1在氯胺酮减轻小胶质细胞活化中的机制研究  

Role of SOCS1 in Ketamine-Induced Inhibition of Microglial Activation

作　　者：雷凤萍 胡斌[2] 王晨[3] 郭琪[2] 胡渤[4] 高淑兰[1] LEI Feng-ping;HU Bin;WANG Chen;GUO Qi;HU Bo;GAO Shu-lan(Department of Pharmacology,Xi'an Aerospace General Hospital,Xi'an,Shaanxi,710100,China;Department ofPharmacology,Xi'an No.4Hospital,Xi'an,Shaanxi,710004,China;3Department of Pharmacology,Tangdu Hospital,Fourth Military Medical University,Xi'an,Shaanxi,710038,China;Department ofAnesthesiology,Xi'an Aerospace General Hospital,Guangzhou,Guangdong,510010,China)

机构地区：[1]西安航天总医院药剂科,陕西西安710100 [2]西安市第四医院药剂科,陕西西安710004 [3]第四军医大学唐都医院药剂科,陕西西安710038 [4]广州军区广州总医院麻醉科,广东广州510010

出　　处：《现代生物医学进展》2018年第22期4219-4223,4239,共6页Progress in Modern Biomedicine

基　　金：广东省医学科研基金项目(A2017526)

摘　　要：目的:探讨麻醉药氯胺酮(Ketamine, KET)对暴露于脂多糖(Lipopolysaccharide, LPS)中的小胶质细胞活化水平的影响,并观察细胞因子信号转导抑制因子1(Suppressor of Cytokine Signaling 1, SOCS1)在其中的作用。方法:本研究选用N9小胶质细胞系,将其暴露于浓度为10 ng/mL的LPS中,模拟炎症反应,同时给与浓度为1 m M的KET,采用Western blot、酶联免疫吸附检测(Enzyme-Linked Immunosorbent Assay, ELISA)小RNA干扰和免疫细胞染色等方法,观察KET对暴露于LPS中的小胶质细胞活化水平的影响,及SOCS1分子在其中的作用。结果:将细胞分为3组,分别为正常培养的Control组、LPS组和KET+LPS组,研究发现,将N9小胶质细胞暴露于含10 ng/mL的细胞培养基中24 h后,细胞诱导型一氧化氮合酶(Inducible Nitric Oxide Synthase, i NOS)表达和培养基肿瘤坏死因子α(Tumor Necrosis Factorα, TNF-α)含量显著增加(P<0.05),而KET可显著降i NOS蛋白表达和培养基TNF-α含量(P<0.05)。随后,将细胞分为5组,分别为Control组、LPS组、KET+LPS组、SOCS1-siRNA+KET+LPS组和乱序siRNA(SC-siRNA)+KET+LPS组,我们发现,LPS可显著增加小胶质细胞TNF-α和白细胞介素1β(Interleukin-1β, IL-1β)的释放、增加SOCS1和核因子κB(Neuclear FactorκB, NF-κB)表达(P<0.05),而KET可显著逆转LPS对炎症因子释放和NF-κB表达的影响,并进一步增加SOCS1表达(P<0.05),而SOCS1-siRNA显著逆转了KET的上述作用(P<0.05),SC-siRNA未对KET产生的上述作用造成显著影响(P>0.05)。结论:KET可降低LPS对小胶质细胞的活化作用,上述作用可能通过SOCS1分子介导。Objective: To explore ketamine (KET)-induced effects on the microglial activation caused by lipopolysaccharide (LPS), and to investigate the role of Suppressor of Cytokine Signaling 1 (SOCS1) in the process. Methods: We took N9 microglial cells, and the cells were exposed to the medium containing LPS of 10 ng/mL to mimic inflammation, meanwhile, 1mM of KET was added into the medium. After the treatments of 24 h, western blot, enzyme-linked immunosorbent assay (ELISA), siRNA interfering and immunocytochemistry were taken to assess the activation of microglia and the role of SOCS1 in the process. Results: The cells were divided into three groups, including control group, LPS group and KET+LPS group, after the treatments, we found that LPS increased the inducible nitric oxide synthase (iNOS) protein expression and Tumor Necrosis Factor α (TNF-α) concentration in the medium (P<0.05), and KET reduced the iNOS expression and TNF-α concentration significantly (P<0.05). Then, the cells were divided into five groups, including control group, LPS group, KET+LPS group, SOCS1-siRNA+KET+LPS group and SC-siRNA+KET+LPS group, after 24-h treatments, we found that LPS increased TNF-α and Interleukin-1β (IL-1β) releases and the protein expressions of SOCS1 and nuclear factor-κB (NF-κB), and KET significantly reversed the effects induced by LPS, and increased SOCS1 expression (P<0.05). However, SOCS1-siRNA, not the SC-siRNA, significantly reversed the KET-induced effects above (P<0.05). Conclusions: KET can reduce LPS-induced microglial activation, and SOCS1 protein may mediate the process.

关 键 词：氯胺酮 炎症 脂多糖 小胶质细胞 细胞因子信号转导抑制因子1 

分 类 号：R-33[医药卫生] Q593.2[生物学—生物化学]