阿魏酸对大气细颗粒物PM2.5诱导的小鼠主动脉炎症的干预作用

Ferulic Acid Inhibits Aortic Inflammation Induced by PM2.5 Through Regulating TLRs Signaling Pathway in Mice

关键词:  阿魏酸  Toll样受体  PM2.5  炎症

Key words:  ferulic acid  Toll-like receptors  PM2.5  inflammatory

摘要:

目的 探讨大气细颗粒物PM2.5对小鼠主动脉Toll样受体（Toll-like receptors，TLRs）信号通路的影响及阿魏酸的干预作用。方法 采用气管滴注方法以10，20 mg·kg^-1的PM2.5处理小鼠，并用40，80 mg·kg^-1的阿魏酸对部分20 mg·kg^-1 PM2.5处理后的小鼠进行治疗。2周后处死小鼠，血液细胞分析仪检测小鼠血液中炎症细胞水平，ELISA检测血清中IL-1β和IL-6的含量，并用荧光定量PCR检测主动脉中IL-1β和IL-6的mRNA水平，Western blot检测各组小鼠主动脉组织中TLR2、TLR4、MyD88、NF-κB p65蛋白的表达，免疫组化技术观察TLR2和TLR4在小鼠主动脉中的水平。结果 PM2.5能提高血液中NEUT、EOS的数量及其在总细胞中的比率，增加血液和主动脉组织中炎症因子IL-1β、IL-6的含量，上调主动脉组织中的TLRs通路相关分子TLR2、TLR4、MyD88、NF-κB p65的表达；而用阿魏酸干预后，血液中白细胞数量、EOS数量、NEUT与EOS的比率明显降低，IL-1β、IL-6水平下降。同时主动脉组织中的TLRs通路相关分子的表达下调。结论 PM2.5可能通过TLRs通路诱导小鼠主动脉炎症的产生，而阿魏酸可能通过抑制TLRs通路相关因子的表达而发挥抑制PM2.5诱导的小鼠主动脉炎症的作用。

Abstract:

OBJECTIVE To investigate the effect of Toll-like receptors (TLRs) signaling pathway on PM2.5-induced inflammation in mice aorta and the intervention of ferulic acid.METHODS Mice were treated with 10, 20 mg·kg^-1 PM2.5 respectively by onsurgical intratracheal instillation. Additionally, mice were concurrently treated with 40, 80 mg·kg^-1 ferulic acid at the high dose group (20 mg·kg^-1 PM2.5) for 2 weeks. The categories of inflammatory cells and inflammatory factors in serum were detected by hemathology analyzer. Isolated aortic tissue was isolated and the mRNA expression of IL-1β and IL-6 were determined by RT-PCR. The protein level of TLR2, TLR4, MyD88 and NF-κB p65 were detected by Western blot. The expression of TLR2 and TLR4 in mice aorta was also evaluated by immunohistochemistry.RESULTS The content and the ratio of NEUT and EOS were increased by PM2.5. The mRNA levels of IL-1β and IL-6 were overexpressed in both blood and aortic tissue. Meanwhile, TLRs signaling pathway-related protein such as TLR2, TLR4, MyD88, and NF-κB p65 were also increased in aortic tissue. After the intervention of ferulic acid, the numbers of NEUT, EOS, and the ratio of NEUT and EOS, as well as the level of inflammation factors including IL-6 and IL-1β were reduced. Moreover, the inhibition TLRs pathway in aortic tissue were also significantly reduced.CONCLUSION PM2.5 can induce the production of aortic inflammation in mice through TLRs signaling pathway. Moreover, ferulic acid can protect mice from PM2.5-induced aortic inflammation by inhibition TLRs pathway.