丹参酮II-A通过调控TLR4/IκBα/NFκB信号通路抑制LPS诱导的细胞炎症  

Tanshinone II-A inhibits LPS induced inflammation of RAW264.7 cells by regulating TLR4/IκB-α/NF-κB signaling pathway

作　　者：侯道荣 刘振[2] 崔斯童 马骏[2] HOU Dao-rong;LIU Zhen;CUI Si-tong;MA Jun(Animal Core Facility of Nanjing Medical University, Nanjing 211166, China;Dept of Neurosurgery, Nanjing Hospital Affiliated to Nanjing Medical University, Nanjing First Hospital, Nanjing 210006, China)

机构地区：[1]南京医科大学医药实验动物中心,江苏南京211166 [2]南京医科大学附属南京医院神经外科,南京市第一医院,江苏南京210006

出　　处：《中国药理学通报》2021年第2期210-214,共5页Chinese Pharmacological Bulletin

基　　金：江苏省中医药局科技项目(NoYB2017093)。

摘　　要：目的建立脂多糖(LPS)诱导的小鼠单核巨噬细胞(RAW264.7)炎症模型,探究丹参酮II-A(Tan IIA)的抗炎活性及其机制。方法CCK-8法测定Tan IIA对细胞活力的影响;迁移小室测定Tan IIA对LPS诱导细胞迁移能力作用;ELISA法测定细胞上清液中小鼠肿瘤坏死因子α(tumor necrosis factoralpha,TNF-α)、白介素6(interleukin 6,IL-6)、IL^-1β、单核细胞趋化蛋白-1(monocyte chemoattractant protein,MCP-1)的含量;Western blot法检测基质金属蛋白酶2(matrix metalloproteinases,MMP-2)、MMP-9、Toll样受体-4(TLR4)、IκB-α、p-IκB-α、NFκB和p-NFκB蛋白的表达。结果Tan IIA对LPS诱导的RAW264.7细胞培养液中炎症因子TNF-α、IL-6、IL^-1β和MCP-1的分泌有明显的抑制作用;明显下调MMP-2、MMP-9、TLR4、p-IκB-α和p-NFκB的蛋白的表达,抑制IκB-α磷酸化和NFκB的入核和活化。结论Tan IIA可通过抑制MMP-2和MMP-9的表达以及TLR4/κB-α/NF-κB信号通路,调控TNF-α、IL-6、IL^-1β等炎症因子的释放而发挥抗炎活性。Aim To establishan inflammatory model of mouse monocyte macrophages(RAW264.7)using lipopolysaccharide(LPS),and to investigate the anti-inflammatory activity and mechanism of tanshinone II-A(Tan IIA).Methods Cell viability was determined by CCK-8 method.Cell migration was detected by Transwell apparatus.TNF-α,IL-6,IL^-1β,MCP-1 content in cell supernatant was analyzed using ELISA method.The protein expression of MMP-2,MMP-9,TLR4,IκB-α,p-IκB-α,NFκB and p-NFκB in RAW264.7 cells was investigated by Western blot.Results Tan IIA significantly inhibited the secretion of TNF-α,IL-6,IL^-1βand MCP-1 in LPS induced RAW264.7 cell culture medium,and significantly down-regulated the expression of matrix metalloproteinase-2(MMP-2),MMP-9,TLR4,p-IκB-αand p-NFκB,inhibited IκB-αphosphorylation and NFκB entry into the nucleus and activation.Conclusion Tan IIA can inhibit the release of inflammatory factors through the regulation of TLR4/IκB-α/NFκB signaling pathway.

关 键 词：丹参酮II-A 脂多糖 RAW264.7细胞 TLR4 IΚBΑ NF-κB 炎症因子 

分 类 号：R-332[医药卫生—中药学] R284.1[医药卫生—中医学]