王 琦,武秀权,戴舒惠,高翔宇,豆雅楠,罗 鹏,李 新.α7nAChR调控STAT3磷酸化在星形胶质细胞机械性损伤后炎症反应中的作用[J].现代生物医学进展英文版,2019,19(15):2845-2849. |
α7nAChR调控STAT3磷酸化在星形胶质细胞机械性损伤后炎症反应中的作用 |
Effects of α7nAChR in Regulation of STAT3 Phosphorylation after Astrocytic Mechanical Injury-induced Inflammation |
Received:February 18, 2019 Revised:March 15, 2019 |
DOI:10.13241/j.cnki.pmb.2019.15.009 |
中文关键词: 创伤性脑损伤 星形胶质细胞 炎症反应 烟碱型乙酰胆碱受体 ?琢7 亚单位 信号传导及转录活化因子3 |
英文关键词: Traumatic brain injury Astrocyte Inflammation Nicotinic acetylcholine receptor alpha 7 subunit Signal transducer and activator of transcription 3 |
基金项目:国家自然科学基金青年科学基金项目(81601149);陕西省高校科协青年人才托举计划项目(20180305);陕西省自然科学基金项目(2017JQ8038) |
Author Name | Affiliation | E-mail | WANG Qi | First Troops of Basic Medicine College, Air Force Medical University, Xi'an, Shaanxi, 710032, China | 176214964@qq.com | WU Xiu-quan | Department of Neurosurgery, Xijing Hospital, Air Force Medical University, Xi'an, Shaanxi, 710032, China | | DAI Shu-hui | Department of Neurosurgery, Xijing Hospital, Air Force Medical University, Xi'an, Shaanxi, 710032, China | | GAO Xiang-yu | Department of Neurosurgery, Xijing Hospital, Air Force Medical University, Xi'an, Shaanxi, 710032, China | | DOU Ya-nan | Department of Neurosurgery, Xijing Hospital, Air Force Medical University, Xi'an, Shaanxi, 710032, China | | LUO Peng | Department of Neurosurgery, Xijing Hospital, Air Force Medical University, Xi'an, Shaanxi, 710032, China | | LI Xin | Department of Anesthesiology, Air Force Medical University, Xi'an, Shaanxi, 710032, China | |
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中文摘要: |
摘要 目的:通过建立星形胶质细胞机械性损伤模型,研究烟碱型乙酰胆碱受体 α7 亚单位(α7nAChR)在创伤性脑损伤后星形胶质细胞炎症反应中的作用及调控机制。方法:建立星形胶质细胞机械性损伤模型,通过ELISA检测炎症因子IL-1β、TNF-α、IL-10和TGF-β的表达;利用α7nAChR抑制剂α-BGT和激动剂PHA-543613处理星形胶质细胞,检测相关炎症因子表达,并通过Western blot检测信号传导及转录活化因子3(STAT3)和磷酸化STAT3(p-STAT3)的表达;利用α-BGT和STAT3抑制剂Stattic处理星形胶质细胞,检测相关炎症因子表达。结果:①星形胶质细胞机械性损伤后,促炎因子IL-1β、TNF-α表达增加,抗炎因子IL-10、TGF-β表达降低(P<0.05)。②利用α-BGT抑制α7nAChR可增加损伤后IL-1β、TNF-α的表达,减少IL-10、TGF-β的表达(P<0.05);而利用PHA-543613激活α7nAChR功能,则发挥相反作用(P<0.05)。③α-BGT可促进STAT3磷酸化,而PHA-543613抑制STAT3磷酸化(P<0.05)。④STAT3抑制剂Stattic可减少IL-1β和TNF-α的表达,增加IL-10和TGF-β的表达,并部分阻断α-BGT对IL-1β、TNF-α、IL-10及TGF-β表达的影响(P<0.05)。结论:机械性损伤后,激活α7nAChR可减轻星形胶质细胞炎症反应,而抑制STAT3磷酸化是其重要的下游机制。 |
英文摘要: |
ABSTRACT Objective: To investigate the role of nicotinic acetylcholine receptor alpha 7 subunit (α7nAChR) in astrocyte-associated inflammation after traumatic brain injury via establishment of astrocytic mechanical injury model. Methods: After establishment of astrocytic mechanial injury, expressions of inflammatory factors, including IL-1β, TNF-α, IL-10, and TGF-β, were detected by ELISA assay. After administration of α7nAChR antagonist (α-BGT) and α7nAChR agonist (PHA-543613), expressions of inflammatory factors were detected by ELISA assay and expressions of STAT3 and STAT3 phosphorylation (p-STAT3) were detected by Western blot. After administration of α-BGT and STAT3 antagonist (Stattic), expressions of inflammatory factors were detected by ELISA assay. Results: ① After astrocytic mechanial injury, expressions of pro-inflammatory factors, IL-1β and TNF-α, were increased, while expressions of anti-inflammatory factors, IL-10 and TGF-β, were decreased (P<0.05). ② Inhibition of α7nAChR by α-BGT increased the expressions of IL-1β and TNF-α after injury and decreased the expressions of IL-10 and TGF-β (P<0.05), while activation of α7nAChR by PHA-543613 showed the reverse effects on these inflammatory facoters (P<0.05). ③Administration of α-BGT increased the phosphorylation of STAT3, while administration of PHA-543613 decreased the phosphorylation of STAT3 (P<0.05). ④Administration of STAT3 antagonist (Stattic) decreased the expressions of IL-1β and TNF-α, increased the expressions of IL-10 and TGF-β, and partially reversed the effects of α-BGT on expressions of IL-1β, TNF-α, IL-10, and TGF-β (P<0.05). Conclusion: After mechanical injury, activation of α7nAChR reduces the inflammation in astrocytes. Inhibition of STAT3 phosphorylation acted as an important downstream mechanism of this process. |
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