ObjectiveTo observe the effect of Huangqi Baihe granules on the hypoxia-inducible factor 1α （HIF-1α）/nuclear factor-κB （NF-κB）/NOD-like receptor hot protein domain related protein 3 （NLRP3） signaling pathway in a rat model of high altitude hypoxia. MethodSixty male SPF SD rats were randomly divided into blank group， model group， dexamethasone group （5 mg·kg^-1）， and high， middle， and low-dose groups of Huangqi Baihe granules （4.1， 2.05， 1.025 g·kg^-1）. Among them， each Chinese medicine group was administrated orally for continuously 14 d， once a day， and the dexamethasone group was injected intraperitoneally for continuously 3 d as the positive control group. On the 15^th d， the model group， dexamethasone group， and high， middle， and low dose groups of Huangqi Baihe granules were exposed to the simulated high altitude， low pressure， and low oxygen environment in the animal low-pressure simulation cabin， and the exposure lasted for 3 d. Blood was collected from the abdominal aorta and serum was separated， and the brain tissue was taken after being killed. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in brain tissue. Enzyme-linked immunosorbent assay （ELISA） was used to detect the content of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β） in rat serum. Western blot was used to detect HIF-1α， NLRP3， phosphorylated nuclear factor-κB （p-NF-κB）， NF-κB， desquamation D （GSDMD）， and cysteine aspartate-specitis protein-1（Caspase-1） in rats of each group. The mRNA expression levels of HIF-1α， NLRP3， NF-κB p65， GSDMD， and Caspase-1 were detected by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultThe results of HE staining showed that as compared with the normal group， the pathological sections of brain tissues in the model group showed that pyramidal cells were loosely arranged and distributed in disorder， with different sizes. Compared with the model group， the pathological changes in pyramidal cells in the dexamethasone group and high and middle-dose groups of Huangqi Baihe granules were reduced. The results of ELISA showed that as compared with the normal group， the content of TNF-α， IL-6， and IL-1β in the serum of rats in the model group was significantly higher （P<0.01）. Compared with the model group， the content of TNF-α， IL-6， and IL-1β in the serum of rats in the dexamethasone group and high and middle-dose groups of Huangqi Baihe granules decreased significantly （P<0.05， P<0.01）. The results of Western blot showed that as compared with the normal group， the relative protein expression levels of HIF-1α， NLRP3， p-NF-κB p65， GSDMD， and Caspase-1 in the brain tissue of the model group were significantly higher （P<0.01）. As compared with the model group， the relative expressions of HIF-1α， NLRP3， p-NF-κB p65， GSDMD， and Caspase-1 in the brain tissue of rats in the dexamethasone group and the high-dose group of Huangqi Baihe granules were significantly decreased （P<0.05， P<0.01）. The relative protein expression levels of HIF-1α， NLRP3， p-NF-κB p65， and Caspase-1 in the brain tissue of rats in the middle-dose group of Huangqi Baihe granules decreased significantly （P<0.01）， and the relative protein expression of HIF-1α in the brain tissue of rats in the low-dose group of Huangqi Baihe granules was reduced （P<0.05）. The Real-time PCR analysis showed that as compared with the normal group， the mRNA expression levels of HIF-1α， NLRP3， NF-κB p65， GSDMD， and Caspase-1 in the brain tissue of the model group were significantly increased （P<0.01）. As compared with the model group， the mRNA expression levels of HIF-1α， NLRP3， NF-κB p65， GSDMD， and Caspase-1 in the brain tissue of rats in the dexamethasone group were significantly decreased （P<0.01）. The mRNA expression levels of HIF-1α， NF-κB p65， GSDMD， and Caspase-1 in the brain tissue of rats in the high-dose group of Huangqi Baihe granules decreased significantly （P<0.01）. The mRNA expression levels of HIF-1α， NLRP3， and Caspase-1in the brain tissue of rats in the middle-dose group of Huangqi granules decreased （P<0.05， P<0.01）. ConclusionThe protective effect of Huangqi Baihe granules on acute brain injury in low-pressure hypoxic rats may be related to the HIF-1α/NF-κB/NLRP3 signaling pathway.

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.