Vanillic Acid Attenuates Monocrotaline-Induced Pulmonary Arterial Hypertension by Enhancing NO Signaling Pathways
Vanillic Acid Attenuates Monocrotaline-Induced Pulmonary Arterial Hypertension by Enhancing NO Signaling Pathways
复制标题
香草酸通过增强 NO 信号通路减轻野百合碱诱发的肺动脉高压
DOI：
10.1177/1934578x221128411
复制
发表时间：
2022-09
影响因子：
1.8
通讯作者：
Zhanqiang Li
中科院分区：
文献类型：
--
作者：
Shan Wang;Xuyang Sun;Zhuguo Wang;Shengjin Zhou;Shanshan Su;Xingmei Nan;Dianxiang Lu;Zhanqiang Li
肺动脉高压（PAH）是一种严重的进展性疾病，其特征为平均肺动脉压升高、右心室肥厚，并最终进展为右心衰竭和死亡。本研究旨在探讨天然产物香草酸（VA）对野百合碱（MCT）诱导的大鼠肺动脉高压的影响。同时还研究了VA的精氨酸酶抑制活性和酶动力学反应。结果表明，VA能够改善MCT诱导的大鼠肺动脉压、肺动脉血管重塑和右心室重塑，并降低肺组织纤维化程度。此外，VA下调了Hif - 2α、Hif - 1β和Arg2的基因及蛋白质表达水平，提高了P - eNOS / eNOS水平，从而增加了肺动脉高压大鼠体内的一氧化氮（NO）水平。进一步研究发现，VA是一种混合竞争性精氨酸酶抑制剂，半数抑制浓度（IC50）为26.1 μM。总之，精氨酸酶抑制剂VA通过增强NO信号通路对MCT诱导的肺动脉高压和肺血管重塑发挥保护作用。
Pulmonary arterial hypertension (PAH) is a severe progressive disease characterized by elevated mean pulmonary arterial pressure, right ventricular hypertrophy, and eventual progression to right heart failure and death. This study aimed to examine the effect of the natural product vanillic acid (VA) on monocrotaline (MCT)-induced PAH in rats. The arginase inhibitory activity and enzyme kinetic reaction of VA were also investigated. The results showed that VA could improve pulmonary arterial pressure, pulmonary artery vascular remodeling, and right ventricular remodeling induced by MCT in rats and reduce the degree of pulmonary tissue fibrosis. Moreover, VA downregulated the gene and protein expression levels of Hif-2α, Hif-1β, and Arg2 and increased the P-eNOS/eNOS levels, thus increasing nitric oxide (NO) levels in PAH rats. Furthermore, VA was determined to be a mixed competitive arginase inhibitor with an IC50 of 26.1 μM. In conclusion, the arginase inhibitor VA exerted protective effects on MCT-induced PAH and pulmonary vascular remodeling by enhancing NO signaling pathways.
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DOI：
10.32383/appdr/149835
发表时间：
2022-06
期刊：
Acta Poloniae Pharmaceutica – Drug Research
影响因子：
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作者：
SHAN WANG;MEIDUO HUAYU;SHANSHAN SU;XINGMEI NAN;DEJUN ZHANG;DIANXIANG LU;ZHANQIANG LI
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DOI：
--
发表时间：
2015
期刊：
--
影响因子：
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影响因子：
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