Chen Tong, Guo Qianqian, Wang Huimin, Zhang Huixin, Wang Ciman, Zhang Ping, Meng Shanshan, Li Yunman, Ji Hui, Yan Tianhua
a State Key Laboratory of Natural Medicines, China Pharmaceutical University , No. 24 Tongjiaxiang, Nanjing 210009, Jiangsu Province , PR China.
b Department of Physiology and Pharmacology , China Pharmaceutical University , Nanjing 210009 , China.
Free Radic Res. 2015;49(12):1459-68. doi: 10.3109/10715762.2015.1087643.
The purpose of the present study was to investigate the protective effect of esculetin (ES) in lipopolysaccharide (LPS)-induced acute lung injury (ALI) and the lung epithelial A549 cells. Mice were intragastrically administered with ES (20 and 40 mg/kg) 1 h prior to LPS challenge. ES pretreatment at doses of 20 and 40 mg/kg effectively attenuated LPS-induced lung histopathological change, myeloperoxidase or MPO activity, inflammatory cells infiltration, pulmonary wet-to-dry weight ratio, and the generation of pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in vivo and in vitro. Furthermore, we demonstrated that ES blocked the activation of NF-кB and RhoA/Rho kinase pathways in LPS-induced mice and A549 cells. The results suggested that ES exhibited protective effect on ALI and might attribute partly to the inhibition of NF-кB and RhoA/Rho kinase pathways in vivo and in vitro.
本研究的目的是探讨七叶亭（ES）对脂多糖（LPS）诱导的急性肺损伤（ALI）及肺上皮A549细胞的保护作用。在LPS攻击前1小时，给小鼠灌胃给予ES（20和40mg/kg）。20和40mg/kg剂量的ES预处理有效减轻了LPS诱导的肺组织病理学变化、髓过氧化物酶或MPO活性、炎症细胞浸润、肺湿干重比以及体内外促炎细胞因子包括肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）的产生。此外，我们证明ES阻断了LPS诱导的小鼠和A549细胞中NF-κB和RhoA/Rho激酶途径的激活。结果表明，ES对ALI具有保护作用，这可能部分归因于其在体内外对NF-κB和RhoA/Rho激酶途径的抑制。
