Baicalein Ameliorates Pulmonary Arterial Hypertension Caused by Monocrotaline through Downregulation of ET-1 and ETAR in Pneumonectomized Rats
Baicalein Ameliorates Pulmonary Arterial Hypertension Caused by Monocrotaline through Downregulation of ET-1 and ETAR in Pneumonectomized Rats
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DOI：
10.1142/s0192415x18500404
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发表时间：
2018-01-01
影响因子：
5.7
通讯作者：
Chou, Tz-Chong
中科院分区：
文献类型：
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作者：
Hsu, Wen-Lin;Lin, Yu-Chieh;Chou, Tz-Chong
从黄芩中提取的黄芩素（BE）能够缓解多种心血管和炎症疾病。然而，BE 对肺动脉高压（PAH）的影响仍不清楚。因此，本研究旨在探讨BE是否能改善大鼠肺切除术和野百合碱诱导的PAH，并进一步研究其潜在的分子机制。 BE 的施用极大地减弱了 PAH 的发展，其特征的改善证明了这一点，包括右心室收缩压升高、右心室肥厚和肺血管重塑。此外，BE 治疗显着逆转了 PAH 大鼠肺部发生的内皮素 1 (ET-1) 和 ETA 受体 (ETAR) 蛋白表达增加、超氧化物过量产生以及 Akt/ERK1/2/GSK3 β/β-catenin 通路激活。与未治疗的PAH大鼠相比，BE治疗的PAH大鼠内皮型一氧化氮合酶（eNOS）表达较高，但诱导型一氧化氮合酶和vWF水平较低。总的来说，BE 治疗可显着减弱 PAH 的发病机制，BE 的保护作用可能与抑制 Akt/Erk1/2/GSK3 beta/beta-catenin/ET-1/ETAR 信号传导和预防内皮功能障碍有关。这些结果表明 BE 是治疗 PAH 的潜在药物。
Baicalein (BE) extracted from Scutellaria baicalensis Georgi is able to alleviate various cardiovascular and inflammatory diseases. However, the effects of BE on pulmonary arterial hypertension (PAH) remain unknown. Therefore, the present study aimed to examine whether BE ameliorates pneumonectomy and monocrotaline-induced PAH in rats and further investigate the underlying molecular mechanisms. Administration of BE greatly attenuated the development of PAH as evidenced by an improvement of its characteristic features, including elevation of right ventricular systolic pressure, right ventricular hypertrophy, and pulmonary vascular remodeling. Moreover, the increased protein expression of endothelin-1 (ET-1) and ETA receptor (ETAR), superoxide overproduction, and activation of Akt/ERK1/2/GSK3 beta/beta-catenin pathway that occurred in the lungs of PAH rats were markedly reversed by BE treatment. Compared with the untreated PAH rats, higher expression of endothelial nitric oxide synthase (eNOS), but lower levels of inducible nitric oxide synthase and vWF were observed in BE-treated PAH rats. Collectively, treatment with BE remarkably attenuates the pathogenesis of PAH, and the protection of BE may be associated with suppressing Akt/Erk1/2/GSK3 beta/beta-catenin/ET-1/ETAR signaling and preventing endothelial dysfunction. These results suggest that BE is a potential agent for treatment of PAH.