目的 研究溪黄草甲素对脂多糖（lipopolysaccharides，LPS）诱导的体内外炎性反应的作用及机制。方法 BALB/c小鼠ip LPS建立急性炎性反应模型，给予溪黄草甲素和地塞米松进行干预，检测各组小鼠血清中肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）和白细胞介素-6（interleukin-6，IL-6）的水平。体外建立LPS诱导的小鼠单核巨噬细胞RAW264.7炎性模型，采用XTT法考察溪黄草甲素对RAW264.7细胞存活率的影响；采用Griess法考察溪黄草甲素对RAW264.7细胞上清液中一氧化氮（nitric oxide，NO）水平的影响；采用ELISA法考察溪黄草甲素对RAW264.7细胞上清液中TNF-α和IL-6水平的影响；采用Western blotting法考察溪黄草甲素对RAW264.7细胞诱导型一氧化氮合酶（inducible nitric oxide synthase，iNOS）、Janus激酶2（Janus kinase 2，JAK2）/信号转导和转录激活因子3（signal transducer and activator of transcription 3，STAT3）、核因子-κB（nuclear factor-κB，NF-κB）、丝裂原活化蛋白激酶（mitogen-activated protein kinase，MAPK）信号通路相关蛋白表达的影响。结果 溪黄草甲素显著抑制LPS诱导的急性炎性小鼠模型血清中TNF-α和IL-6水平（P<0.05、0.01、0.001）。溪黄草甲素（≤5 μmol/L）对RAW264.7细胞存活率无明显影响；溪黄草甲素显著抑制LPS诱导的RAW264.7细胞NO分泌和上清液中TNF-α、IL-6水平，以及iNOS、磷酸化JAK2（p-JAK2）和磷酸化STAT3（p-STAT3）蛋白表达水平（P<0.05、0.01、0.001），但对NF-κB和MAPK信号通路相关蛋白表达无抑制作用。结论 溪黄草甲素能够抑制LPS诱导的体内外炎性反应，其作用机制可能与抑制JAK2/STAT3信号通路有关。

Objective To study the effect and mechanism of rabdoserrin A on lipopolysaccharides (LPS)-induced inflammatory response in vivo and in vitro. Methods BALB/c mice were ip LPS to establish an acute inflammatory response model, rabdoserrin A and dexamethasone were used for intervention, levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in serum of mice in each group were detected. LPS-induced inflammatory model of RAW264.7 cells was established in vitro, and XTT method was used to investigate the effect of rabdoserrin A on survival rate of RAW264.7 cells; Griess was used to investigate the effect of rabdoserrin A on nitric oxide (NO) level in supernatant of RAW264.7 cells; ELISA was used to investigate the effect of rabdoserrin A on levels of TNF-α and IL-6 in supernatant of RAW264.7 cells; Western blotting was used to investigate the effect of rabdoserrin A on expressions of inducible nitric oxide synthase (iNOS), Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3), nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathway related protein in RAW264.7 cells. Results Rabdoserrin A significantly inhibited the levels of TNF-α and IL-6 in the serum of acute inflammation mice model induced by LPS (P < 0.05, 0.01, 0.001). Rabdoserrin A (≤ 5 μmol/L) had no significant effect on survival rate of RAW264.7 cells; Rabdoserrin A significantly inhibited NO secretion, levels of TNF-α and IL-6 in supernatant, expressions of iNOS, phosphorylated JAK2 (p-JAK2) and phosphorylated STAT3 (p-STAT3) in RAW264.7 cells induced by LPS (P < 0.05, 0.01, 0.001), but had no inhibitory effect on expressions of NF-κB and MAPK signaling pathways related protein. Conclusion Rabdoserrin A can inhibit the inflammatory response induced by LPS in vivo and in vitro, and its mechanism may be related to the inhibition of JAK2/STAT3 signaling pathway.

R285.5

国家自然科学基金资助项目（81973458）