The First School of Clinical Medicine, Southern Medical University, Guangzhou, China.
Department of Cardiovascular Surgery, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, China.
J Healthc Eng. 2022 Mar 24;2022:1890892. doi: 10.1155/2022/1890892. eCollection 2022.
Tetramethylpyrazine (TMP), a potent anti-free radical and anti-inflammations substance, has been demonstrated to possess a direct vessel relaxation property. This study aimed to evaluate the effect of TMP treatment in pulmonary hypertension (PH) and test the hypothesis that TMP prevents or reverses the process of PH.
Rats ( = 36) injected with 50 mg/kg of monocrotaline (MCT) subcutaneously 4 weeks to develop PH were then randomized to TMP (5 mg/kg per day) for another 4 weeks. Hemodynamics was evaluated via the right ventricle. Pulmonary vessels structural remodeling and inflammation were examined by histologic and transmission electron microscopy observation. The expression of inducible nitric oxide synthase (iNOS) and cGMP-dependent protein kinases 1 (PKG-1) was detected by immunohistochemical staining and Western blot. Generation of reactive oxygen species (ROS) and antioxidation species was measured by biochemical analyses.
MCT increased PH and right ventricle hypertrophy. TMP alleviated pulmonary arterial pressure elevation, leukocyte infiltration, and structural remodeling of pulmonary arterials induced by MCT successfully. TMP treatment significantly increased the PKG-1 expression and suppressed the iNOS expression. The activity of superoxide dismutase (SOD), glutathione peroxidase (GSH), and catalase (CAT) was significantly higher than control group, while malondialdehyde (MDA) levels were lower compared with MCT group.
TMP can suppress established MCT-induced PH through the ROS/iNOS/PKG axis. The underlying mechanisms may be associated with its anti-inflammatory, antioxidant, and antiproliferative properties in pulmonary arterial.
四甲基吡嗪（TMP）是一种有效的抗自由基和抗炎物质，已被证明具有直接的血管舒张特性。本研究旨在评估 TMP 治疗肺动脉高压（PH）的效果，并验证 TMP 可预防或逆转 PH 进程的假设。
皮下注射 50mg/kg 野百合碱（MCT）4 周的大鼠（ = 36）发展为 PH，然后随机分为 TMP（5mg/kg/天）治疗 4 周。通过右心室评估血液动力学。通过组织学和透射电子显微镜观察评估肺血管结构重塑和炎症。通过免疫组化染色和 Western blot 检测诱导型一氧化氮合酶（iNOS）和环鸟苷酸依赖性蛋白激酶 1（PKG-1）的表达。通过生化分析测量活性氧（ROS）和抗氧化物质的产生。
MCT 增加了 PH 和右心室肥大。TMP 成功缓解了 MCT 诱导的肺动脉压力升高、白细胞浸润和结构重塑。TMP 治疗显著增加了 PKG-1 的表达并抑制了 iNOS 的表达。超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH）和过氧化氢酶（CAT）的活性明显高于对照组，而丙二醛（MDA）水平低于 MCT 组。
TMP 可通过 ROS/iNOS/PKG 轴抑制已建立的 MCT 诱导的 PH。其潜在机制可能与其在肺动脉中的抗炎、抗氧化和抗增殖特性有关。
