Quercetin alleviates acute lung injury by enhancing alveolar macrophage efferocytosis based on PPARγ/LXR-α signaling pathway
Objective It is to observe the effect of quercetin on alveolar macrophage efferocytosis in rats with acute lung injury and investigate its potential mechanism based on the peroxidase proliferator-activated receptor γ(PPARγ)/hepatic X receptor α(LXR-α)signaling pathway.Methods Sixty male SD rats were divided into 6 groups,with 10 rats in each group.The low,medium,and high dose groups of quercetin were respectively given 10 mg/kg,50 mg/kg,and 100 mg/kg of quercetin by gavage,the dexamethasone group was given 5 mg/kg of dexamethasone by gavage,and the normal group and lipopolysaccharide group were given equal amounts of normal saline by gavage,all once daily.After 14 days of continu-ous gavage,all the groups except for the normal group were given lipopolysaccharide by nasal drip method to establish acute lung injury models.At 24 h after modeling,the alveolar macrophage efferocytosis of rats in each group was detected,the apoptosis rate of lung tissue was detected by TUNEL,the serum levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6),interleukin-10(IL-10)were detected by ELISA,the pathological morphology of lung tis-sues was observed by HE staining,and the positive expressions of HPARγ,PPARγ,and IL-10 proteins in lung tissue were detected by immunohistochemical method,and the expressions of PPARγ,LXR-α,CD68 mRNA in lung tissues were de-tected by RT-PCR.Results Compared with the normal group,the efferocytosis of alveolar macrophages of rats in the lipopo-lysaccharide group was significantly weakened(P＜0.05),the proportion of apoptosis in lung tissue and the serum levels of TNF-α,IL-1β and IL-6 were significantly increased(all P＜0.05),the serum level of IL-10 was significantly decreased(P＜0.05),the lung cells were swollen and degenerated,with much inflammatory cell infiltration,the mean optical densi-ty values of positive expressions of PPARγ,LXR-α,and CD68 proteins and the relative expression of their mRNA in lung tissues were significantly decreased(all P＜0.05).Compared with the lipopolysaccharide group,the efferocytosis of alveo-lar macrophages of rats in each quercetin group and dexamethasone group was significantly enhanced(all P＜0.05),the proportion of apoptosis in lung tissue and the serum levels of TNF-α,IL-1β and IL-6 were significantly decreased in the medium and high dose groups of quercetin and dexamethasone group(all P＜0.05),the serum levels of IL-10 were signifi-cantly increased in each quercetin group(all P＜0.05),the pathological injury of lung tissues were significantly improved in the high dose group of quercetin,the mean optical density values of positive expressions of PPARγ,LXR-α,and CD68 proteins and the relative expression of their mRNA in lung tissues in the medium and high dose groups of quercetin were significantly higher than those in the lipopolysaccharide group(all P＜0.05),the mean optical density values of positive expressions of PPARγ and CD68 proteins and the relative expression of PPARγ,LXR-α mRNA in lung tissues in the dexa-methasone group were significantly higher than those in the lipopolysaccharide group(all P＜0.05).Conclusion Quercetin can enhance the efferocytosis of alveolar macrophages and alleviate the pathological injury of lung tissue in rats with lipopo-lysaccharids-induced acute lung injury,and its mechanism may be related to the up-regulation of PPARγ/LXR-α signaling pathway.
acute lung injuryquercetinalveolar macrophageefferocytosisperoxidase proliferator-activated recep-tor γhepatic X receptor αrat
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