| 摘要: | 急性肺損傷(Acute lung injury; ALI)是造成患者死亡一個重要的成因。如何抗發炎的治療或是改善ALI患者的預後是重要的課題，己有許多文獻指出中醫藥在對抗肺部急性發炎有其成效，而銀翹散便是其中對抗肺部急性發炎重要的方劑，但其抗發炎的機制仍然不清楚。
為了研究銀翹散對抗肺部急性發炎的機制，我們以氣管投與LPS誘發老鼠肺部急性發炎，同時餵食銀翹散，結果發表不論在肺部發炎的病理組織上、中性白血球的浸潤數量、肺部水腫指標及一氧化氮分泌的量上，皆可見到銀翹散有減緩肺部發炎的成效。我們以ELISA 及 RT-PCR 來偵測各種發炎相關的細胞激素及趨化因子，如TNFα、IL-1β、 IL-6、KC、MCP-1及MIP-2，銀翹散皆有壓制的作用，同時我們也發現銀翹散可誘發大量的抗發炎細胞激素IL-10的分泌。我們利用鼠巨噬細胞RAW 264.7針對TNFα及IL-10 進行體外研究。銀翹散、銀花、連翹及牛蒡對LPS誘發產生TNF-α有明顯壓抑作用，荊芥、薄荷及淡竹葉少許壓制作用。而銀翹散及金銀花可以增加LPS誘發分泌IL-10。
由銀翹散的HPLC成份分析中，找到銀翹散指標成分綠原酸、木犀草素、牛蒡素及橙皮素，其中最大量的成份為綠原酸，我們也證實綠原酸會增加LPS誘發RAW 264.7分泌IL-10；另外我們也發現橙皮素可抑制A549及THP-1的TNFα、IL-1β、IL-6、IL-8的分泌，同時結果也顯示橙皮素可抑制發炎細胞的附著作用及ICAM-1與VCAM-1的表現。我們進一步發現銀翹散橙皮素可減少NF-κB與AP-1對其控制序列結合作用，並且橙皮素可阻斷IκB 及MAPK 路徑。因此，銀翹散有抑制LPS造成的肺部發炎作用及免疫調節作用，有助於急性肺部發炎的治療。
To investigate the effects of Gingyo-san (GGS), traditional Chinese medicinal formula, on the acute lung inflammation induced by LPS in vivo. Mice were challenged with intratracheal LPS before with treatment GGS or vehicle. In Lung morphology, GGS is better than Xia-Bai-San (XBS) and Hesperidin that reducing the infiltration of activated polymorphonuclear neutrophils in the airways, decreasing pulmonary edema, reduced nitrosative stress, and improved lung morphology. ELISA or RT-PCR detected the expression of cytokines in BALF and lung tissue. The mechanism of these benefits by treatment GGS including attenuating expression TNFα, IL-1β, IL-6, KC, MCP-1, MIP-2, iNOS, and activation of nuclear factor (NF-κB and AP-1) in BALF and lung tissue. Particularly, GGS also enhanced the anti-inflammatory cytokine (IL-10) and limited the acute lung inflammation. In vitro, HES suppressed the expression of IL-8 on A549 cells and THP-1 cells, the expression of TNFα, IL-1β, and IL-6 on THP-1 cells, the expression of ICAM-1 and VCAM-1 on A549 cells which effect cell adhesion function. The suppression of those molecules is controlled by NF-κB and AP-1, which are activated by IκB and MAPK pathways. We also demonstract that GGS, Flos Lonicera, and chlorogenic acid induce the IL-10 secretion in LPS-induced RAW 264.7 cell lines.
Therefore, GGS protection activity against LPS-induced lung inflammatory mediators release and might be beneficial in the treatment of endotoxin-associated inflammation. |
