Yang Ning, Liu Yu-Ying, Pan Chun-Shui, Sun Kai, Wei Xiao-Hong, Mao Xiao-Wei, Lin Fang, Li Xue-Jun, Fan Jing-Yu, Han Jing-Yan
Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China; Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China; Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, China; Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of China, Beijing, China.
Microcirculation. 2014 Nov;21(8):703-16. doi: 10.1111/micc.12152.
The purpose of this study was to explore the protective effect of AP on LPS-induced PMD and ALI.
Male SD rats were continuously infused with LPS (5 mg/kg/h) for one hour to induce PMD and ALI. AP was administrated orally one hour before LPS exposure. Arterial blood pressure and HR were monitored. Blood gas analysis, histological observation, cytokines in plasma, leukocyte recruitment, pulmonary oxidative stress, microvessel permeability, edema, and related proteins were evaluated six hours after LPS challenge.
Rats receiving LPS exhibited significant alterations, including hypotension, tachycardia, increase in cytokines, neutrophil adhesion and infiltration, oxidative stress, and microvessel hyperpermeability, resulting in pulmonary injury and dysfunction. AP (0.18 g/kg or 1.8 g/kg) improved rat survival rate, and significantly attenuated all aforementioned insults, and inhibited LPS-induced increase in adhesion molecules, up-regulation of Cav-1 and Src kinase and NADPH oxidase subunits (p47(phox) and p67(phox) ) membrane translocation in lung tissue, and preserved JAM-1 and claudin-5.
The results demonstrated the protective effect of AP on LPS-induced PMD and ALI, suggesting the potential of AP as a prophylactic strategy for LPS-induced ALI.
本研究旨在探讨穿心莲内酯（AP）对脂多糖（LPS）诱导的肺微血管损伤（PMD）和急性肺损伤（ALI）的保护作用。
雄性SD大鼠连续1小时输注LPS（5mg/kg/h）以诱导PMD和ALI。在暴露于LPS前1小时口服给予AP。监测动脉血压和心率。在LPS攻击6小时后评估血气分析、组织学观察、血浆细胞因子、白细胞募集、肺氧化应激、微血管通透性、水肿及相关蛋白。
接受LPS的大鼠表现出显著变化，包括低血压、心动过速、细胞因子增加、中性粒细胞黏附和浸润、氧化应激及微血管高通透性，导致肺损伤和功能障碍。AP（0.18g/kg或1.8g/kg）提高了大鼠存活率，并显著减轻了所有上述损伤，抑制了LPS诱导的肺组织中黏附分子增加、Cav-1和Src激酶及NADPH氧化酶亚基（p47（phox）和p67（phox））膜转位上调，并保留了JAM-1和claudin-5。
结果证明了AP对LPS诱导的PMD和ALI具有保护作用，提示AP作为LPS诱导ALI预防性策略的潜力。
