The effect of nestorone on pulmonary inflammation in lipopolysaccharides-induced acute lung injury
Objective:To investigate the regulatory effect of nestorone(NES)on lipopolysaccharides(LPS)-induced acute lung injury(ALI)model by in vivo and in vitro experiments.Methods:A549 cells were cultured to analyze the cell survival rate by MTT and the pro-inflammatory cytokines by enzyme-linked immunosorbent assay(ELISA).A mouse model of LPS-induced ALI was established and pre-treated with NES.The acute inflammatory response within lung was evaluated by total cell counts,differential cell counts in bronchoalveolar lavage fluid(BALF),the degree of lung inflammation in each group by H&E,the lung ratio of wet and dry,and total proteins in BALF.Then the protective effect of NES on survival status was examined by LPS-induced ALI model.Results:In A549 cells,there was no cytotoxicity in the experimental concentrations(10-4~100 μmol·L-1),and NES(1 and 10 μmol·L-1)significantly inhibited LPS-induced inflammatory cytokines production.In the LPS-induced ALI mouse model,NES pre-treatment significantly attenuated the acute inflammatory response and damage in lung,including reducing the number of total cells,neutrophils,macrophages,and lymphocytes in BALF,reducing proteins exudation,and decreasing the expression of inflammatory cytokines(IL-6,CXCL-1 and TNF-α).The survival time and survival rate were increased by NES.Conclusion:NES has potent anti-inflammatory activity in LPS-induced A549 cells and ALI mouse model,prolong the survival period and increase the survival rate of ALI mice.