连翘酯苷A通过TLR4/NF-κB抑制PC12细胞低氧/再复氧诱导的炎症反应

Forsythiaside A inhibits inflammation induced by cerebral ischemia through TLR4/NF-κB

目的研究连翘酯苷A(FA)对缺血再灌注诱导的PC12细胞炎症反应的抑制作用。方法建立PC12细胞氧糖剥夺/再灌注(OGD/R)模型,给予不同浓度的FA(1.25、2.5和5μmol/L)处理,测定炎症因子:白细胞介素(IL)-1β、肿瘤坏死因子-α(TNF-α)和IL-6的水平,Western blot测定TLR4/NF-κB通路相关蛋白的表达情况,并采用慢病毒激活颗粒进行机制验证。结果 FA可显著抑制炎症因子释放水平,抑制TLR4和NF-κB p65蛋白表达水平,同时可抑制细胞核内NF-κB p65表达。分别采用Toll样受体4 (TLR4)和核转录因子kappa B (NF-kB)慢病毒激活颗粒验证发现FA通过TLR4调控NF-κB p65核转移,从而抑制炎症因子释放,减轻炎症反应。结论 FA可通过调控TLR4抑制NF-κB p65核转移抑制炎症因子表达,从而减轻缺血再灌注诱导的炎症反应,发挥脑保护作用。

Objective To study the inhibitory effect of forsythoside A(FA) on the inflammation induced by ischemia/reperfusion in PC12 cells.Methods Oxygen glucose deprivation/reoxygenation(OGD/R) model was established in PC12 cells, and PC12 cells were treated with different concentrations of FA(1.25, 2.5 and 5 μmol/L) to determine inflammatory factors(IL-1β, TNF-α and IL-6) level, Western blot was used to determine the expression of toll-like receptor-4(BTLR4);nuclear factor kappa(NF-κB) pathway-related proteins, and the mechanism was verified using lentiviral activation particles.Results FA could significantly inhibit the release of inflammatory factors, inhibit the protein expression of TLR4 and NF-κB p65, and also inhibit the expression of NF-κB p65 in the nucleus. TLR4 and NF-κB lentiviral activation particles were used to verify that FA regulated NF-κB p65 nuclear transfer through TLR4, thereby inhibiting the release of inflammatory factors and reducing inflammation.Conclusion FA can inhibit the expression of inflammatory factors by inhibition of NF-κB p65 nuclear translocation regulated by TLR4, so as to reduce the inflammatory response induced by ischemia-reperfusion and show brain protection effects.