Gao Rong, Wu Zhenhui, Dang Wanyun, Yang Tingyu, Chen Junru, Cheng Hongbo, Cui Jialu, Lin Lin, Shen Xin, Li Fangyang, Yan Jiayi, Gao Yehui, Gao Yue, Ma Zengchun
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Beijing Institute of Radiation Medicine, Beijing 100859, China.
Int J Mol Sci. 2025 Mar 13;26(6):2584. doi: 10.3390/ijms26062584.
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 CD3CD4 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 CD3CD4 T cells and the CD4/CD8 cell ratio in peripheral blood and the spleen, while increasing CD4IFN-γcells 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.
本研究旨在建立低压低氧诱导的免疫损伤模型，并探讨黄芪甲苷（AS-IV）的干预及治疗作用。本研究模拟海拔7000米高原环境对小鼠进行低压低氧刺激1、3、5和7天。对小鼠脾脏进行苏木精-伊红（HE）染色及转录组分析。此外，选用AS-IV进行防治干预，并通过流式细胞术、酶联免疫吸附测定（ELISA）和实时荧光定量聚合酶链反应（Q-PCR）进行验证。结果显示，在海拔7000米模拟低氧条件下5天时，小鼠外周血淋巴细胞减少，脾脏中CD45细胞、CD3 T细胞、CD3CD4 T细胞及CD4/CD8细胞比值均降低。AS-IV可显著减轻脾脏病理损伤，降低血清白细胞介素-2（IL-2）和白细胞介素-6（IL-6）水平，升高IL-4和IL-10水平，提高外周血及脾脏中CD3CD4 T细胞及CD4/CD8细胞比值，同时增加脾脏中CD4干扰素-γ（IFN-γ）细胞，降低脾脏中活性氧（ROS）及细胞凋亡水平，并增加Th1/Th2细胞途径中相关mRNA的含量。综上所述，模拟海拔7000米低氧5天可建立稳定的低压低氧免疫损伤模型，AS-IV可有效减轻低压低氧免疫损伤。
