Heart Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, China.
College of pharmacy, Xinjiang Medical University, Urumqi, 830011, China.
BMC Complement Med Ther. 2023 May 6;23(1):150. doi: 10.1186/s12906-023-03981-2.
Oxidative stress and endothelial cell dysfunction induced by high-altitude hypoxia have important roles in the pathological process of high-altitude pulmonary hypertension (HAPH). Tannins present in Terminalia bellirica (Gaertn.) Roxb. (TTR) have pharmacological activities that produce oxidation resistance and exert anti-inflammatory effects. Whether TTR exerts a protective effect on HAPH remains unknown.
A rat model of HAPH was established. The mean pulmonary arterial pressure (mPAP) of the animals was measured, the serum levels of SOD, MDA, and GSH-Px were measured using ELISA, and the expression of Bax, Bcl-2, Nrf2, and HO-1 proteins in the lung tissue of each group of rats was measured using Western blotting. Pathological changes in the lung tissue were also observed. A model of damage to HO-induced pulmonary artery endothelial cells (PAECs) was generated, and cell proliferation was measured using CCK-8 assays. Flow cytometry was used to measure ROS levels in PAECs. Western blotting was used to detect the expression of Bax, Bcl-2, Nrf2, and HO-1 proteins in PAECs.
The hemodynamic and pathologic findings showed that the mPAP of HAPH rats increased markedly, and the vascular wall thickness increased (P < 0.05). TTR reduced mPAP, alleviated or slowed pulmonary arterial remodeling, increased GSH-Px and SOD activity, lowered the level of MDA (P < 0.05), and downregulated the expression of Bax in the lung tissues of HAPH rats, while the expression of Bcl-2, Nrf2, and HO-1 was upregulated (P < 0.05). The results of the cell experiments showed that TTR inhibited HO-induced PAEC apoptosis and ROS production (P < 0.05), downregulated the expression of Bax in PAECs, and upregulated the expression of Bcl-2, Nrf2, and HO-1 (P < 0.05).
The results suggest that TTR reduces pulmonary arterial pressure, decreases oxidative stress during HAPH, and exerts protective effects in rats with HAPH and that its mechanism of action is related to regulation of the Nrf2/HO-1 signaling pathway.
高空缺氧引起的氧化应激和内皮细胞功能障碍在高原性肺动脉高压（HAPH）的病理过程中起重要作用。五倍子（Terminalia bellirica（Gaertn.）Roxb.）中存在的单宁具有抗氧化和抗炎作用的药理活性。五倍子是否对 HAPH 有保护作用尚不清楚。
建立大鼠 HAPH 模型。测量动物的平均肺动脉压（mPAP），使用 ELISA 测量血清中超氧化物歧化酶（SOD）、丙二醛（MDA）和谷胱甘肽过氧化物酶（GSH-Px）的水平，并用 Western blot 测量各组大鼠肺组织中 Bax、Bcl-2、Nrf2 和 HO-1 蛋白的表达。还观察了肺组织的病理变化。建立 HO 诱导的肺动脉内皮细胞（PAECs）损伤模型，用 CCK-8 法测量细胞增殖。用流式细胞术测量 PAECs 中的 ROS 水平。用 Western blot 检测 PAECs 中 Bax、Bcl-2、Nrf2 和 HO-1 蛋白的表达。
血流动力学和病理学发现 HAPH 大鼠的 mPAP 明显升高，血管壁厚度增加（P<0.05）。五倍子降低 mPAP，减轻或延缓肺动脉重塑，增加 GSH-Px 和 SOD 活性，降低 MDA 水平（P<0.05），下调 HAPH 大鼠肺组织中 Bax 的表达，同时上调 Bcl-2、Nrf2 和 HO-1 的表达（P<0.05）。细胞实验结果表明，五倍子抑制 HO 诱导的 PAEC 凋亡和 ROS 产生（P<0.05），下调 PAECs 中 Bax 的表达，上调 Bcl-2、Nrf2 和 HO-1 的表达（P<0.05）。
结果表明，五倍子降低 HAPH 时的肺动脉压，降低氧化应激，对 HAPH 大鼠具有保护作用，其作用机制与调节 Nrf2/HO-1 信号通路有关。
