Dihydromyricetin prevents monocrotaline-induced pulmonary arterial hypertension in rats
Dihydromyricetin prevents monocrotaline-induced pulmonary arterial hypertension in rats
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二氢杨梅素可预防野百合碱诱导的大鼠肺动脉高压
DOI：
10.1016/j.biopha.2017.10.007
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发表时间：
2017-12-01
影响因子：
7.5
通讯作者：
Yu, Jun
中科院分区：
文献类型：
--
作者：
Li, Qinghai;Wang, Jun;Yu, Jun
肺动脉高压（PAH）是一种慢性致死性疾病，目前缺乏有效的治疗方法。本研究旨在探讨2 R，3R-二氢杨梅素（DHM）是否能预防野百合碱（MCT）诱导的大鼠PAH。注射MCT的大鼠接受生理盐水或DHM（100 mg/kg体重/天）处理4周，随后测量右心室收缩压（RVSP）、右心室肥大指数（RVHI）、肺动脉重塑（PAR）和IL-6、TNF-α和IL-10的表达水平。在体外，我们评估了DHM对IL-6诱导的原代人肺动脉平滑肌细胞（HPASMCs）迁移的作用。我们发现，DHM治疗减弱了MCT注射PAH大鼠的RVSP、RVHI和PAR变化。DHM治疗可抑制PAH大鼠中观察到的IL-6水平升高。在体外，DHM预处理减少IL-6诱导的HPASMC迁移。此外，在体内和体外，DHM处理抑制了MCT和IL-6介导的MMP 9和P-STAT 3（tyr 705）PY-STAT 3水平升高。这些结果表明，DHM可以通过抑制STAT 3/MMP 9轴来防止MCT诱导的大鼠PAH和IL-6诱导的HPASMC迁移。
Pulmonary artery hypertension (PAH) is a chronic and deadly disease, for which effective medical treatments are lacking. Here, we investigated whether 2R, 3R-dihydromyricetin (DHM) could prevent monocrotaline (MCT)induced PAH in rats. The MCT-injected rats were treated with normal saline or DHM (100 mg/kg body weight/d) for 4 weeks, followed by measurements of right ventricular systolic pressure (RVSP), right ventricular hypertrophy index (RVHI), pulmonary arterial remodeling (PAR), and expression levels of IL-6, TNF-alpha, and IL-10. In vitro, we assessed the role of DHM on IL-6-induced migration of primary human pulmonary arterial smooth muscle cells (HPASMCs). We found that DHM treatment attenuated changes in RVSP, RVHI, and PAR in MCTinjected PAH rats. The observed increase of IL-6 levels in PAH rats was inhibited by DHM treatment. In vitro, DHM pretreatment reduced IL-6-induced HPASMC migration. Furthermore, MCT-and IL-6-mediated increases in MMP9 and P-STAT3 (tyr705) PY-STAT3 levels were suppressed by DHM treatment in vivo and in vitro. These results suggest that DHM could prevent MCT-induced rat PAH and IL-6-induced HPASMC migration through a mechanism involving inhibiting of the STAT3/MMP9 axis.