Cao Chengzhu, Zhang Huan, Huang Yongchun, Mao Yameng, Ma Lan, Zhang Shoude, Zhang Wei
Research Center for High-Altitude Medicine, Key Laboratory for High-Altitude Medicine, Ministry of Education, Qinghai University, Xining, China.
Medical College of Qinghai University, Qinghai University, Xining, China.
Ann Transl Med. 2022 May;10(10):541. doi: 10.21037/atm-22-2111.
Altitude sickness (AS), which is caused by rapid exposure to low amounts of oxygen at high elevations, poses a great threat to humans working and traveling in these conditions. Acute mountain sickness includes high-altitude pulmonary edema and high-altitude cerebral edema. Acetazolamide (AZ) is often used to treat pulmonary edema caused by hypoxia. Additionally, the medicinal plant . () is often used to prevent AS in the Qinghai-Tibet plateau. However, the mechanisms of action of and AZ in the treatment of AS remain unclear. To date, no research has been conducted to determine whether their combined use has better efficacy in the treatment and prevention of AS than their separate use.
We used the method of network pharmacology to analyze the mechanisms of and AZ in combination in the prevention and treatment of AS, and also verified our results.
The hypoxia-inducible factor (HIF)-1 signaling pathway, which is related to hypoxia, and other pathways related to pulmonary hypertension, became more enriched after the combined use of the 2 drugs. Additionally, and AZ regulated most nodes in the AS network. Further, compared to their separate use, the combined use of and AZ further downregulated the gene expression of HIF-1α and improved hemodynamics in rats, and thus helped the body to reduce its sensitivity to hypoxic environments and pulmonary artery pressure.
This study provides evidence supporting the combined use of AZ and in the treatment of AS.
高原病(AS)是由在高海拔地区快速暴露于低氧环境引起的,对在这些条件下工作和旅行的人构成了巨大威胁。急性高原病包括高原肺水肿和高原脑水肿。乙酰唑胺(AZ)常用于治疗由缺氧引起的肺水肿。此外,药用植物(此处原文缺失植物名称)常用于预防青藏高原的高原病。然而,该植物和AZ在治疗高原病中的作用机制仍不清楚。迄今为止,尚未进行研究来确定它们联合使用在治疗和预防高原病方面是否比单独使用具有更好的疗效。
我们使用网络药理学方法分析该植物和AZ联合预防和治疗高原病的机制,并对结果进行了验证。
与缺氧相关的缺氧诱导因子(HIF)-1信号通路以及与肺动脉高压相关的其他通路在两种药物联合使用后变得更加富集。此外,该植物和AZ调节了高原病网络中的大多数节点。此外,与单独使用相比,该植物和AZ联合使用进一步下调了大鼠HIF-1α的基因表达并改善了血流动力学,从而帮助身体降低对低氧环境和肺动脉压力的敏感性。
本研究为AZ和该植物联合用于治疗高原病提供了证据支持。