Ruscogenin attenuates particulate matter-induced acute lung injury in mice via protecting pulmonary endothelial barrier and inhibiting TLR4 signaling pathway

• 作者: Yu-wei Wang Yun-hao Wu Jia-zhi Zhang Jia-hui Tang Rui-ping Fan Fang Li Bo-yang Yu Jun-ping Kou Yuan-yuan Zhang
• 来源期刊: 中国药理学报（英文版）
• 年，卷（期）: 2021,（5）
• 所属期刊栏目: Pulmonary Pharmacology
• 页码范围: 726-734
• 页数: 9页
• 语种: 英文

摘要

The inhalation of particulate matter (PM) is closely related to respiratory damage,including acute lung injury (ALl),characterized by inflammatory fluid edema and disturbed alveolar-capillary permeability.Ruscogenin (RUS),the main active ingredient in the traditional Chinese medicine Ophiopogonisjoponicus,has been found to exhibit anti-inflammatory activity and rescue LPS-induced ALl.In this study,we investigated whether and how RUS exerted therapeutic effects on PM-induced ALl.RUS (0.1,0.3,1 mg.kg-1·d-1) was orally administered to mice prior to or after intratracheal instillation of PM suspension (50 mg/kg).We showed that RUS administration either prior to or after PM challenge significantly attenuated PM-induced pathological injury,lung edema,vascular leakage and VE-cadherin expression in lung tissue.RUS administration significantly decreased the levels of cytokines IL-6 and IL-1β,as well as the levels of NO and MPO in both bronchoalveolar lavage fluid (BALF) and serum.RUS administration dosedependently suppressed the phosphorylation of NF-KB p65 and the expression of TLR4 and MyD88 in lung tissue.Furthermore,TLR4 knockout partly diminished PM-induced lung injury,and abolished the protective effects of RUS in PM-instilled mice.In conclusion,RUS effectively alleviates PM-induced ALl probably by inhibition of vascular leakage and TLR4/MyD88 signaling.TLR4 might be crucial for PM to initiate pulmonary lesion and for RUS to exert efficacy against PM-induced lung injury.