Effects of apple polyphenols on monocrotaline-induced pulmonary vascular remodeling in rats and its mechanism

doi:10.12047/j.cjap.5769.2019.045

Abstract

Abstract: Objective: To investigate the effects of apple polyphenols on pulmonary vascular remodeling in rats with pulmonary arterial hypertension and its mechanism. Methods: Rats were randomly divided into 4 groups:control (Con) group, monocrotaline (MCT) group, apple polyphenol (APP) group,monocrotaline + apple polyphenol (MCT+APP) group. In Con group, rats received a subcutaneous injection of physical saline. In APP group, rats received intraperitoneal injection of 20 mg/kg APP, every other day. In MCT group, rats received a single subcutaneous injection of MCT(60 mg/kg). In MCT+APP group, rats received subcutaneous injection of 60 mg/kg MCT followed by an intraperitoneal injection of 20 mg/kg APP every other day. All the disposal lasted 3 weeks. Then the PAH-relevant indicators, such as mean pulmonary artery pressure(mPAP), pulmonary vascular resistance(PVR), right ventricular hypertrophy index (RVHI) ,wall thickness (WT%) and wall area (WA%) were tested. After that, the inflammatory pathway related indicators, such as interleukin1(IL-1),interleukin1(IL-6), tumor necrosis factor α(TNF-α), cyclooxygenase 2(COX-2) and myeloperoxidase(MPO) in pulmonary tissue and free intracellular Ca²⁺ in pulmonary smooth muscle cell(PASMC), content of eNOS and NO in endothelial cells were determined. Results: Compared with the control group, the levels of mPAP, PVR, RVHI, WA%, WT%, and IL-1, IL-6, TNF-α, COX-2, MPO in tissue and the expression of Ca^{2 +} in PASMC of MCT group were increased significantly, while the contents of eNOS and NO in endothelial cells were decreased significantly (P＜0.05). Compared with the MCT group, the apple polyphenol treatment could improve the above mentioned situation, and the COX-2 and Ca²⁺ indicators of the apple polyphenol treatment group were decreased significantly (P＜0.05). Conclusion: MCT can increase COX-2 expression and intracellular Ca²⁺ in pulmonary artery smooth muscle cells, decrease the contents of eNOS and NO in endothelial cells, while apple polyphenols can significantly inhibit these effects.

Key words: apple polyphenol, pulmonary arterial hypertension, pulmonary arterial smooth muscle cell, rat, COX-2, intracellular Ca²⁺

ZHANG Shu-hao, SHAO Si-ming, CHEN Fang-zheng, ZHU Jing, CHEN Luo-wei, WANG heng, XIANG Xin-hui, YUAN Lin-bo. Effects of apple polyphenols on monocrotaline-induced pulmonary vascular remodeling in rats and its mechanism[J]. CJAP, 2019, 35(3): 209-214.

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