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 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.
Division of Respiratory Medicine, Taizhou Enze Medical Center Enze Hospital, Taizhou, Zhejiang 318000, China.
Shuangquan
0000-0002-7460-1410
S
Yan
Division of Equipment, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
Yiran
Y
Wang
Division of Intensive Care Unit, Ningbo Medical Center Lihuili Eastern Hospital, Ningbo, Zhejiang 315040, China.
Panpan
0000-0002-0142-0600
P
Liu
Division of Pulmonary Medicine, The First Affiliated Hospital of Wenzhou Medical University and Key Laboratory of Heart and Lung, Wenzhou, Zhejiang 325035, China.
Ali
A
Chen
Division of Pulmonary Medicine, The First Affiliated Hospital of Wenzhou Medical University and Key Laboratory of Heart and Lung, Wenzhou, Zhejiang 325035, China.
Mayun
M
Chen
Division of Pulmonary Medicine, The First Affiliated Hospital of Wenzhou Medical University and Key Laboratory of Heart and Lung, Wenzhou, Zhejiang 325035, China.
Dan
D
Yao
Division of Pulmonary Medicine, The First Affiliated Hospital of Wenzhou Medical University and Key Laboratory of Heart and Lung, Wenzhou, Zhejiang 325035, China.
Xiaomei
X
Xu
Division of Pulmonary Medicine, The First Affiliated Hospital of Wenzhou Medical University and Key Laboratory of Heart and Lung, Wenzhou, Zhejiang 325035, China.
Liangxing
L
Wang
Division of Pulmonary Medicine, The First Affiliated Hospital of Wenzhou Medical University and Key Laboratory of Heart and Lung, Wenzhou, Zhejiang 325035, China.
Xiaoying
0000-0003-4854-0922
X
Huang
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