Rong Gao

This study aims to establish a hypobaric hypoxia-induced immune injury model and investigate the intervention and therapeutic effects of Astragaloside IV (AS-IV). This study simulated hypobaric hypoxia stimulation in mice at an altitude of 7000 m on a plateau for 1, 3, 5, and 7 days. HE staining and transcriptomic analysis were performed on mouse spleens. In addition, AS-IV was selected for intervention in prevention and treatment, and validated by flow cytometry, ELISA, and Q-PCR. The results showed that under simulated hypoxic conditions at an altitude of 7000 m for 5 days, the peripheral blood lymphocytes of mice decreased, and the CD45⁺ cells, CD3⁺ T cells, and CD3⁺CD4⁺ T cells, and CD4⁺/CD8⁺ cell ratio in the spleen all decreased. AS-IV can significantly alleviate pathological damage to the spleen, decrease serum levels of IL-2 and IL-6, increase IL-4 and IL-10, and raise CD3⁺CD4⁺ T cells and the CD4⁺/CD8⁺ cell ratio in peripheral blood and the spleen, while increasing CD4⁺IFN-γ⁺cells in spleen, reducing ROS and apoptosis levels in spleen, and increasing the content of relevant mRNA in the Th1/Th2 cell pathway. In summary, simulating hypoxia at an altitude of 7000 m for 5 days can establish a stable hypobaric hypoxic immune injury model, and AS-IV can effectively alleviate hypobaric hypoxic immune injury.

Plateau hyperuricemia is a common disease in the plateau area, and the incidence is much higher than that in the plain area. Dioscin (DIO) and its active metabolite Diosgenin (DG) exert therapeutic effects on hyperuricemia through oxidative stress and inflammation. In this study, DIO and its active metabolite DG were taken as the research objects to explore their therapeutic effects on high-altitude hyperuricemia in rats. To evaluate the therapeutic effect of DIO on the rat model of high-altitude hyperuricemia, the evaluation indexes include blood biochemical indexes, renal histopathology, oil red O staining of the kidney, rat kidney index, and rat renal inflammatory factors. Transcriptomics was used to analyze the control group, model group, and drug-administered group to preliminarily explore the protective mechanism of DIO in rats with high-altitude hyperuricemia. An HK-2 high-altitude hyperuricemia cell injury model was established to verify the therapeutic mechanism of DIO in rats with high-altitude hyperuricemia. Western blot was used to detect the expression of related proteins in renal tissues and cell models. The results showed that DIO and its active metabolite DG regulate renal lipid metabolism through the EPHX2 gene, attenuate renal inflammatory reaction, and then promote the excretion of uric acid and reduce its reabsorption, which ultimately achieves the effect of treating plateau hyperuricemia.

This study aimed to investigate the protective effects of ginsenoside Rg1 on high-altitude hypoxia-induced acute lung injury (ALI) and elucidated its molecular targets and related pathways, specifically its association with the fluid shear stress pathway. Using a combination of bioinformatics analysis and both in vivo and in vitro experiments, we assessed the role of ginsenoside Rg1 in mitigating physiological and biochemical disturbances induced by hypoxia. In the in vivo experiments, we measured arterial blood gas parameters, levels of inflammatory cells and cytokines, erythrocyte and platelet parameters, and conducted histological analysis in rats. The in vitro experiments utilized human pulmonary microvascular endothelial cells (HPMECs) and A549 cells to examine cell viability, intracellular reactive oxygen species (ROS) and Ca²⁺ levels, and mitochondrial function. The results of the in vivo experiments demonstrate that ginsenoside Rg1 significantly increased arterial blood oxygen partial pressure and saturation, elevated arterial blood glucose levels, and stabilized respiratory and metabolic functions in rats. It also reduced inflammatory cells and cytokines, such as tumor necrosis factor-α and interleukin-6, and improved erythrocyte and platelet abnormalities, supporting its protective role through the regulation of the fluid shear stress pathway. Histological and ultrastructural analyses revealed that Rg1 significantly protected lung tissue structure and organelles. In vitro experiments further confirmed that Rg1 improved cell viability in HPMEC and A549 cells under hypoxic conditions, decreased intracellular ROS and Ca²⁺ levels, and enhanced mitochondrial function. These findings collectively demonstrate that ginsenoside Rg1 exerts significant protective effects against high-altitude hypoxia-induced ALI by enhancing oxygen delivery and utilization, reducing inflammatory responses, and maintaining cellular metabolism and vascular function. Notably, the protective effects of Rg1 are closely associated with the regulation of the fluid shear stress pathway, suggesting its potential for treating high-altitude hypoxia-related diseases.