Targeting MALAT1 and miRNA-181a-5p for the intervention of acute lung injury/acute respiratory distress syndrome |
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| LI Congyi, CAO Wangjie, HUANG Yong, SU Yun, GONG Hongxia, LENG Guangxian, LI Lixia, ZENG Yuanding. Intervention Effect of Dabufei Decoction on Acute Lung Injury in Rats with High Altitude Hypoxia Based on HIF-1α/NLRP3 Signaling Pathway[J]. Chinese Journal of Modern Applied Pharmacy, 2024, 41(6): 736-742. DOI: 10.13748/j.cnki.issn1007-7693.20223230 |
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| Authors: | LI Congyi CAO Wangjie HUANG Yong SU Yun GONG Hongxia LENG Guangxian LI Lixia ZENG Yuanding |
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| Affiliation: | 1.School of Basic Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou 730000, China;2.Gansu Provincial Key Laboratory of Molecular Medicine and Traditional Chinese Medicine for Major Diseases, Lanzhou 730000, China;3.Key Laboratory of Dunhuang Medicine and Transformation at Provincial and Ministerial Level, Lanzhou 730000, China;4.The Second Hospital of Lanzhou University, Lanzhou 730000, China;5.Tianshui Integrated Traditional Chinese and Western Medicine Hospital, Tianshui 741000, China |
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| Abstract: | OBJECTIVE To investigate the intervention effect of Dabufei decoction on acute lung injury in rats with high altitude hypoxia by regulating the expression of the HIF-1α/NLRP3 signaling pathway and related molecules. METHODS Sixty SPF SD rats were randomly divided into blank group, model group, positive drug group, Dabufei decoction high-dose, medium-dose, and low-dose groups with 10 rats in each group. After 3 d of adaptation to feeding, the rats in the blank group and model group were given the same amount of normal saline by gavage, and the rats in Dabufei decoction high-dose, medium-dose, and low-dose groups were given gavage for 14 d, respectively. The positive drug group was given dexamethasone by intraperitoneal injection for three consecutive days before entering the chamber. Except for the blank group, the rats in each group were exposed to hypoxia in the experimental animal low-pressure simulation chamber from the 15th day for three consecutive days. At the end of the experiment, the wet to dry ratio(W/D) of the rat lung tissue was detected. The morphology of lung tissue was observed by HE staining. ELISA detected the levels of IL-1β and IL-18 in serum. Western blotting and RT-qPCR were used to detect the protein and mRNA expressions of HIF-1α, NLRP3, GSDMD, and caspase-1 in the lung tissue of rats. RESULTS The W/D value showed that compared with the blank group, the W/D of the model group was significantly increased(P<0.01). Compared with the model group, the W/D of rats in the positive drug group, Dabufei decoction high-dose group, medium-dose, and low-dose groups was significantly decreased(P<0.01 or P<0.05). HE results showed that compared with the blank group, alveolar septum thickening, pulmonary interstitial congestion, edema, inflammatory cell infiltration, and a small amount of exudation in the alveolar cavity were seen in the lung tissue of the model group. Compared with the model group, the thickening of alveolar walls in the positive drug group, Dabufei decoction high-dose group, medium-dose, and low-dose groups were reduced, and the pulmonary interstitial congestion, edema, and inflammatory cell infiltration were significantly reduced. ELISA results showed that IL-1β and IL-18 in rat serum were significantly higher in the model group than in the blank group(P<0.01). Compared with the model group, the levels of IL-1β and IL-18 in the serum of the rats in the positive drug group, Dabufei decoction high-dose group, medium-dose, and low-dose groups were significantly decreased(P<0.05 or P<0.01). Moreover, the results of Western blotting and RT-qPCR showed that compared with the blank group, the relative protein and mRNA expressions of HIF-1α, NLRP3, GSDMD, and caspase-1 in the lung tissue of the model group were significantly increased(P<0.01). Compared with the model group, the relative protein and mRNA of HIF-1α, NLRP3, caspase-1 and GSDMD in the positive drug group and Dabufei decoction high-dose group were significantly decreased(P<0.05 or P<0.01), the relative protein of HIF-1α, NLRP3, caspase-1 and GSDMD in Dabufei decoction medium-dose group were significantly decreased and HIF-1α, caspase-1 mRNA were significantly decreased(P<0.05), the relative protein of HIF-1α and GSDMD in the low-dose group was decreased(P<0.05). The positive drug group and Dabufei decoction high-dose group had the more significant effect. CONCLUSION Dabufei decoction can regulate the HIF-1α/NLRP3 signaling pathway, inhibit pyroptosis and reduce inflammation, and has a certain protective effect on acute lung injury in rats with high altitude hypoxia. |
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| Keywords: | acute lung injury high altitude hypoxia HIF-1α NLRP3 Dabufei decoction inflammatory response |
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