蛞蝓提取物对LPS致小鼠气道及肺部急性炎症的影响

Effects of Limax Extract on LPS-induced Acute Inflammation of Airway and Pulmonary in Mice

关键词:  蛞蝓  急性肺损伤  中性粒细胞  气道炎症

Key words:  Limax  acute lung injury  neutrophil  airway inflammation

摘要:

目的 探讨蛞蝓提取物对脂多糖（lipopolysaccharide，LPS）致小鼠气道及肺部急性炎症的影响。方法 将48只C57BL/6雄性小鼠随机分为正常对照组（Ctl）、正常对照+蛞蝓干预组（Ctl+Limax）、模型组（LPS）、模型+蛞蝓干预组（LPS+Limax），每组12只。各蛞蝓干预组于造模前1 d起给予4.36 g·kg^-1蛞蝓提取物灌胃，每日1次，直至造模结束。经鼻滴入LPS对小鼠进行急性气道炎症造模，非造模组经鼻滴入同体积生理盐水。观测各组小鼠肺病理、肺的髓过氧化物酶表达；肺泡灌洗液中白细胞及IL-6、CXCL1、TNF-α、IFN-γ的分泌；采用LC-MS对蛞蝓提取物进行主成分分析，计算机模拟分子对接推测可能的活性成分。结果 蛞蝓提取物可明显缓解LPS致小鼠急性气道炎症的肺组织病理，减少肺部的白细胞浸润，抑制肺部髓过氧化物酶表达，降低肺泡灌洗液中IL-6、CXCL1、TNF-α、IFN-γ含量，其中活性成分可能是黄酮Ononin，且与Siglecs受体有潜在结合可能。结论 蛞蝓提取物具有明显的抑制急性气道炎症的作用，其中活性成分黄酮Ononin通过Siglecs受体抑制中性粒细胞浸润可能是其改善急性肺损伤病理的作用机制之一。

Abstract:

OBJECTIVE To explore the effects of Limax on LPS-induced acute inflammation of airway and pulmonary in mice. METHODS Forty eight C57BL/6 male mice were randomly divided into normal control group (Ctl), normal control plus Limax intervention group (Ctl+ Limax), model group (LPS) and model plus Limax intervention group (LPS+ Limax), with 12 mice in each group. Each Limax intervention group was given 4.36 g·kg^-1 Limax extract daily by gavage from the day before modeling until the day of modeling. LPS was dripped through the nose to model the acute airway inflammation in mice, and the non-made model was dripped with the same volume of normal saline. The pathologic changes and myeloperoxidase expression of lung tissue in each group were observed. White blood cell count and white blood cell classification in bronchoalveolar lavage fluid(BALF) were performed, and the content of IL-6, CXCL1, TNF-α and IFN-γ in BALF were determined. Principal component analysis of Limax extract was performed using LC-MS and molecular docking in silico was performed to infer the possible active components. RESULTS Limax extract could improve the pulmonary pathologic changes of mice in each group, alleviate the infiltration of white blood cell, decrease the myeloperoxidase expression in lung tissue and the content of IL-6, CXCL1, TNF-α and IFN-γ in BALF. The active components might be Ononin, which had the possibility binding to Siglecs. CONCLUSIONS Limax extract can inhibit the acute airway inflammation obviously, and the active component of Ononin inhibits neutrophil infiltration through Siglecs receptor, may be one of its mechanisms of improving the pathology of acute lung injury.