Effects of ganoderma acid A on lipopolysaccharide-induced acute lung injury in mice and its mechanism
- VernacularTitle:灵芝酸A对脂多糖诱导的小鼠急性肺损伤的改善作用及机制
- Author:
Hui WANG
1
;
Zhu ZHANG
;
Jun WANG
Author Information
- Keywords: ganoderic acid A; acute lung injury; in-flammation; oxidative stress; NLR family Pyrin domain protein 3(NLRP3); pyroptosis
- From: Chinese Pharmacological Bulletin 2024;40(8):1559-1565
- CountryChina
- Language:Chinese
- Abstract: Aim To investigate the effect of ganoderic acid A(GAA)on lipopolysaccharide(LPS)-induced acute lung injury(ALI)in mice and the underlying mechanism.Methods The mice were randomly di-vided into control group,model group,low-dose GAA group(GAA-L group)and high-dose GAA group(GAA-H group),with 12 mice in each group.ALI was induced by intratracheal instillation of LPS(5 mg·kg-1).The mice in GAA-L group and GAA-H group were intraperitoneally injected with 50 mg/kg GAA and 150 mg·kg-1 GAA,respectively,at 30 min before ALI.Twelve hours after modeling,bronchoalve-olar lavage fluid(BALF)was collected,and the total cells and neutrophils in BALF were counted,and the contents of TNF-α and IL-1 β were detected.The liver was collected,and the wet/dry lung weight ratio was obtained by weighing method.HE staining was used to observe the morphological characteristics of lung tis-sue,and the levels of MDA,ROS,GSH and SOD in lung tissue were detected.The protein expressions of NLRP3,ASC,Caspase-1 and GSDMD in lung tissue were detected by Western blot.Results Compared with the model group,ALI score and wet/dry ratio of lung tissue decreased in both low and high dose GAA groups(P＜0.05),and the pathological damage was alleviated,the contents of total cells,neutrophils,IL-1 β and TNF-α in BALF decreased(P＜0.05),and the expressions of MDA,NLRP3,ASC,caspase-1 and GSDMD proteins in lung tissues were down-regulated(P＜0.05),GSH and SOD levels increased(P＜0.05),and the effect of high-dose group was signifi-cantly better than that of low-dose group(P＜0.05).Conclusions GAA has a protective effect on the lung of ALI mice,and its mechanism may be related to in-hibiting NLRP3/GSDMD signaling pathway,reducing inflammatory response,oxidative stress and inhibiting pyroptosis.
