Resveratrol downregulates acute pulmonary thromboembolism-induced pulmonary artery hypertension via p38 mitogen-activated protein kinase and monocyte chemoattractant protein-1 signaling in rats

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• 作者：Chen Chun^a ; Wang Yang^b ; ¹ ; Cai Xueding^a ; ¹ ; Zhang Qi^c ; Huang Xiaoying^a ; Xu Honglei^a ; Yu Fangyou^d ; Chen Chan^a ; Lu Yuanyuan^a ; Zhang Weixi^e ; Yao Dan^a ; Zhang Zhoucang^f ; Yang Lehe^a ; Ding Cheng^a ; Wang Liangxing^a ; ^{wzyxywlx@163.com}
• 关键词：Resveratrol ; Acute pulmonary thromboembolism ; Pulmonary artery hypertension ; Monocyte chemoattractant protein-1 ; Phosphorylated p38 mitogen-activated protein kinase
• 刊名：Life Sciences
• 出版年：2012
• 期刊代码：62_00243205
• 类别：imm
• 出版时间：22 May, 2012
• 卷：90
• 期：19-20
• 页码：721-727
• 文件大小：1325 K

摘要

Aims

In the present study, we explored the hypothesis that initiation of PH involves the upregulation of monocyte chemoattractant protein-1 (MCP-1) in acute PTE. We evaluated the effects of resveratrol and the role of p38 mitogen-activated protein kinase (MAPK) in this process.

Main methods

A rat model of acute PTE was established by infusion of an autologous blood clot into the pulmonary artery through a polyethylene catheter. Rats were randomly divided into 1, 4, and 8 hour time groups. Resveratrol, C1142 (a rodent chimeric mAb that neutralizes rat MCP-1) or SB203580 (a p38MAPK specific inhibitor) was administered to the animals beginning 1 h prior to the start of the acute PTE protocol. At each time point, the mean pulmonary artery pressure (mPAP), mRNA and protein expressions of MCP-1 were measured. The phosphorylation of p38 MAPK (p-pMAPK) was also detected.

Key findings

Acute PTE elicited significant increases in mean pulmonary artery pressure (mPAP), and up-regulated the expression of monocyte chemoattractant protein-1 (MCP-1) and phosphorylation of p38 mitogen-activated protein kinase (p-p38 MAPK). Administration of C1142 markedly reduced mPAP. Furthermore, pre-treatment of rats with resveratrol significantly reduced mPAP and down-regulated the expression of MCP-1, which was associated with robustly suppressed acute PTE-induced p-p38MAPK expression.

Significance

These findings suggested that MCP-1 was involved in the formation of acute PTE-induced PH, and resveratrol down-regulated the expression of MCP-1 by inhibiting acute PTE-induced p-p38MAPK activation, which contributed to the decrease in PH.