Baicalin Attenuates Hypoxia-Induced Pulmonary Arterial Hypertension to Improve Hypoxic Cor Pulmonale by Reducing the Activity of the p38 MAPK Signaling Pathway and MMP-9.

Baicalin Attenuates Hypoxia-Induced Pulmonary Arterial Hypertension to Improve Hypoxic Cor Pulmonale by Reducing the Activity of the p38 MAPK Signaling Pathway and MMP-9.
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黄芩苷通过降低 p38 MAPK 信号通路和 MMP-9 的活性减轻缺氧引起的肺动脉高压,改善缺氧性肺心病

DOI:
10.1155/2016/2546402
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发表时间:
2016
期刊:
Evidence-based complementary and alternative medicine : eCAM
影响因子:
--
通讯作者:
Huang X
Huang X
中科院分区:
其他
文献类型:
--
作者:
Yan S;Wang Y;Liu P;Chen A;Chen M;Yao D;Xu X;Wang L;Huang X

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黄芩苷对大鼠缺氧性肺动脉高压有保护作用,但其作用机制尚不清楚。因此,研究这种效应的潜在机制是本研究的目的。成功制备了对照组低氧性肺动脉高压和肺心病模型大鼠。我们通过一系列指标观察肺动脉高压、肺动脉小动脉重构和右心室重构的水平。我们分别使用免疫组织化学和western blot分析评估了p38丝裂原活化蛋白激酶(MAPK)在肺小动脉壁和肺组织匀浆中的活化情况。采用免疫组织化学和原位杂交技术检测肺小动脉壁基质金属蛋白酶- (MMP-) 9蛋白和mRNA水平。我们的研究结果表明,黄芩苷不仅降低了肺小动脉壁和组织匀浆中p38 MAPK的激活,而且下调了肺小动脉壁中MMP-9蛋白和mRNA的表达水平。这种下调伴随着肺动脉高压、小动脉重构和右心室重构的减弱。提示黄芩苷可能通过下调p38 MAPK/MMP-9通路,减轻慢性缺氧所致的肺动脉高压和肺源性心脏病。
Baicalin has a protective effect on hypoxia-induced pulmonary hypertension in rats, but the mechanism of this effect remains unclear. Thus, investigating the potential mechanism of this effect was the aim of the present study. Model rats that display hypoxic pulmonary hypertension and cor pulmonale under control conditions were successfully generated. We measured a series of indicators to observe the levels of pulmonary arterial hypertension, pulmonary arteriole remodeling, and right ventricular remodeling. We assessed the activation of p38 mitogen-activated protein kinase (MAPK) in the pulmonary arteriole walls and pulmonary tissue homogenates using immunohistochemistry and western blot analyses, respectively. The matrix metalloproteinase- (MMP-) 9 protein and mRNA levels in the pulmonary arteriole walls were measured using immunohistochemistry and in situ hybridization. Our results demonstrated that baicalin not only reduced p38 MAPK activation in both the pulmonary arteriole walls and tissue homogenates but also downregulated the protein and mRNA expression levels of MMP-9 in the pulmonary arteriole walls. This downregulation was accompanied by the attenuation of pulmonary hypertension, arteriole remodeling, and right ventricular remodeling. These results suggest that baicalin may attenuate pulmonary hypertension and cor pulmonale, which are induced by chronic hypoxia, by downregulating the p38 MAPK/MMP-9 pathway.
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