Yadav Seema, Singh Somnath, Singh Mrinalini
Experimental Biology Division, Defence Institute of Physiology and Allied Science, Defence Research and Development Organization, Lucknow Road, Timarpur, Delhi, 110 054, India.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Apr 14. doi: 10.1007/s00210-025-04118-7.
Tanshinone IIA (Tan-IIA), derived from Salvia miltiorrhiza, has been used in traditional Chinese medicine to treat cardiovascular diseases and pulmonary hypertension. This study investigates the potential of Tan-IIA preconditioning as a protective strategy against hypoxia-induced lung injury. Male Sprague-Dawley rats (200 ± 25 g) were divided into four groups: normoxia, normoxia with Tan-IIA, hypobaric hypoxia, and hypobaric hypoxia with Tan-IIA. Tan-IIA was administered intraperitoneally at doses of 10, 20, and 40 mg/kg body weight one hour before exposure to hypobaric hypoxia (simulated altitude of 25,000 feet for 48 h). Pulmonary edema was assessed by measuring transvacuolar leakage of sodium fluorescein dye and lung water content. Exposure to hypoxia triggered redox imbalances, inflammation, and changes in levels of nitric oxide (NOx), endothelin- 1, and Na/K ATPase, which contributed to pulmonary edema. Tan-IIA preconditioning, particularly at 20 mg/kg, was effective in reversing these disturbances. Tan-IIA modulated the expression of key signaling molecules, including c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38, as well as downstream activator protein- 1 (AP- 1) subunits (Jun and Fos), thus reducing inflammation. Its protective effects were partly due to increased NO levels and decreased endothelin, which lowered pulmonary vasoconstriction and permeability, respectively. Additionally, enhanced Na/K ATPase expression via hypoxia-inducible factor- 1 (HIF- 1) and AP- 1 pathways promoted alveolar fluid clearance, while interactions between nuclear factor erythroid 2-related factor 2 (Nrf2) and c-Jun highlighted the anti-oxidative properties of Tanshinone IIA. These findings demonstrate that Tanshinone IIA preconditioning protects against hypoxia-induced lung injury by mitigating pulmonary leakage. This highlights its potential therapeutic application in hypoxic lung conditions.
丹参酮IIA（Tan-IIA）源自丹参，在传统中药中用于治疗心血管疾病和肺动脉高压。本研究探讨Tan-IIA预处理作为一种针对缺氧诱导的肺损伤的保护策略的潜力。雄性Sprague-Dawley大鼠（200±25克）分为四组：常氧组、Tan-IIA常氧组、低压缺氧组和Tan-IIA低压缺氧组。在暴露于低压缺氧（模拟海拔25,000英尺48小时）前1小时，以10、20和40毫克/千克体重的剂量腹腔注射Tan-IIA。通过测量荧光素钠染料的跨液泡渗漏和肺含水量来评估肺水肿。暴露于缺氧会引发氧化还原失衡、炎症以及一氧化氮（NOx）、内皮素-1和钠钾ATP酶水平的变化，这些都会导致肺水肿。Tan-IIA预处理，尤其是20毫克/千克的剂量，能有效逆转这些紊乱。Tan-IIA调节关键信号分子的表达，包括c-Jun氨基末端激酶（JNK）、细胞外信号调节激酶（ERK）和p38，以及下游激活蛋白-1（AP-1）亚基（Jun和Fos），从而减轻炎症。其保护作用部分归因于一氧化氮水平的升高和内皮素的降低，分别降低了肺血管收缩和通透性。此外，通过缺氧诱导因子-1（HIF-1）和AP-1途径增强钠钾ATP酶的表达促进了肺泡液体清除，而核因子红细胞2相关因子2（Nrf2）和c-Jun之间的相互作用突出了丹参酮IIA的抗氧化特性。这些发现表明，丹参酮IIA预处理通过减轻肺渗漏来保护免受缺氧诱导的肺损伤。这突出了其在缺氧性肺疾病中的潜在治疗应用。
