Effect and Mechanism of Oenothera biennis L. Extract on Acute Lung Injury Induced by LPS in Rats
ZHANG Qin-qin1,2, LIU Juan-juan1,2, LÜ Ya-xin1,2, ZHAO Chen-xin1, FAN Ru-yi1, ZENG Meng-nan1,2,3, ZHANG Bei-bei1,2, FENG Wei-sheng1,2,3, ZHENG Xiao-ke1,2,3*
1. Henan University of Chinese Medicine, Zhengzhou 450046, China; 2. The Engineering and Technology Center for Chinese Medicine Development of Henan Province, Zhengzhou 450046, China; 3. Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-Constructed by Henan Province and Education Ministry of P. R. C, Zhengzhou 450046, China
Abstract：OBJECTIVE To investigate the effect of Oenothera biennis L. extract on lipopolysaccharide-induced acute lung injury in rats and explore its mechanism. METHODS The rat model of acute lung injury(ALI) was established by intranasal inoculation of 10 mg·kg-1 lipopolysaccharide. A total of 40 male SD rats were randomly divided into control group(CON), model group(LPS), low-dose Oenothera biennis L. extract group(YJC-L) and high-dose Oenothera biennis L. extract group(YJC-H). After the model was established, test drug was continuously administered intragastrically for 3 d, hematoxylin-eosin(HE) staining was used to observe the pathological changes of lung tissue. Enzyme-linked immunosorbent assay(ELISA) was used to detect the contents of interleukin-6(IL-6), interferon-γ(IFN-γ) and tumor necrosis factor-α(TNF-α) in bronchoalveolar lavage fluid of each group. Enzymatic method was used to detect the contents of glutathione peroxidase(GSH-Px), superoxide dismutase(SOD) and malondialdehyde(MDA) in rat lung tissue. Flow cytometry was used to detect the levels of apoptosis and ROS in primary lung cells. Western blot was used to detect the contents of nuclear factor E2-related factor 2(Nrf2), NOD-like receptor protein 3(NLRP3), cysteinyl aspartate specific proteinase 1(caspase-1), cleaved cysteinyl aspartate specific proteinase 1(cleaved-caspase-1), gasdermin D(GSDMD) and cleaved gasdermin D(cleaved-GSDMD). RESULTS Compared with the CON, the alveolar cavity was disappeared, the alveolar wall was thickened and the inflammatory cells around the alveolar increased significantly in the LPS group. The contents of IL-6 and TNF-α increased significantly in bronchoalveolar lavage fluid(P<0.01), while IFN-γ decreased significantly(P<0.01). The contents of GSH-Px and SOD decreased significantly(P<0.01), while the content of MDA increased significantly(P<0.01). The levels of apoptosis and ROS of primary lung cells were increased (P<0.01), and the protein expression levels of Nrf2, NLRP3, caspase-1, cleaved-caspase-1, GSDMD and cleaved-GSDMD were significantly increased(P<0.01). Compared with the LPS group, the Oenothera biennis L. extract could significantly improve the pathological morphology of lung. The levels of IL-6 and TNF-α were significantly decreased(P<0.01 or P<0.05), and IFN-γ was significantly increased(P<0.01). The levels of GSH-Px and SOD increased significantly(P<0.01 or P<0.05), and the level of MDA was decreased. The levels of apoptosis and ROS were decreased in primary lung cells, the expression level of Nrf2 protein was upregulated(P<0.01 or P<0.05), while the protein expression levels of NLRP3, caspase-1, cleaved-caspase-1, GSDMD and cleaved-GSDMD were downregulated(P<0.01 or P<0.05). CONCLUSIONOenothera biennis L. extract can improve LPS-induced ALI by reducing the levels of inflammation, oxidative stress and apoptosis. This effect might be mediated by Nrf2-NLRP3 pathway.
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2023, Vol. 58 
