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Updated: Feb 20, 2026
The Left Pneumonectomy Combined with Monocrotaline or Sugen as a Model of Pulmonary Hypertension in Rats
Published on: March 8, 2019
Dihydromyricetin prevents monocrotaline-induced pulmonary arterial hypertension in rats
Qinghai Li1, Jun Wang1, Xianying Zhu1
1Department of Respiratory and Critical Care Medicine, National Clinical Research Center of Respiratory Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Abstract:
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 (100mg/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-α, 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 MCT-injected 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.
Insights
2R,3R-dihydromyricetin (DHM) shows promise in preventing pulmonary artery hypertension (PAH) in rats. DHM treatment reduced key markers of PAH and inhibited cell migration by targeting the STAT3/MMP9 pathway.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Cell Biology
Background:
- Pulmonary artery hypertension (PAH) is a severe condition with limited treatment options.
- Monocrotaline (MCT) is a known inducer of experimental PAH in animal models.
- Understanding novel therapeutic targets is crucial for managing PAH.
Purpose of the Study:
- To investigate the preventative effects of 2R,3R-dihydromyricetin (DHM) on monocrotaline (MCT)-induced pulmonary artery hypertension (PAH) in rats.
- To explore the in vitro efficacy of DHM in mitigating IL-6-induced pulmonary arterial smooth muscle cell migration.
- To elucidate the molecular mechanisms underlying DHM's potential therapeutic action in PAH.
Main Methods:
- Rats were injected with MCT and subsequently treated with DHM or saline for 4 weeks.
- Key hemodynamic and structural parameters of PAH were measured, including right ventricular systolic pressure (RVSP) and pulmonary arterial remodeling (PAR).
- In vitro studies assessed DHM's effect on IL-6-stimulated human pulmonary arterial smooth muscle cells (HPASMCs), focusing on migration, MMP9, and STAT3 phosphorylation.
Main Results:
- DHM treatment significantly attenuated MCT-induced increases in RVSP, RVHI, and PAR in rats.
- DHM inhibited elevated IL-6 levels in PAH rats and reduced IL-6-induced HPASMC migration in vitro.
- Both in vivo and in vitro, DHM suppressed MCT- and IL-6-mediated increases in MMP9 and phosphorylated STAT3 (P-STAT3) levels.
Conclusions:
- DHM demonstrates preventative efficacy against MCT-induced PAH in a rat model.
- DHM inhibits IL-6-induced HPASMC migration, suggesting a role in vascular remodeling.
- The findings indicate that DHM's protective effects are mediated through the inhibition of the STAT3/MMP9 signaling axis.
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