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CJAP ›› 2019, Vol. 35 ›› Issue (3): 209-214.doi: 10.12047/j.cjap.5769.2019.045

• ORIGINAL ARTICLES • Previous Articles     Next Articles

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

ZHANG Shu-hao1+, SHAO Si-ming2+, CHEN Fang-zheng1, ZHU Jing1, CHEN Luo-wei1, WANG heng3, XIANG Xin-hui2, YUAN Lin-bo4△   

  1. 1. School of the First Clinical Medical Sciences, Wenzhou Medical University;
    2. Ren ji College of Wenzhou Medical University;
    3. College of Optometry, Wenzhou Medical University;
    4. Department of Physiology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325000, China
  • Online:2019-05-28 Published:2019-06-28

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 Ca2 + 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+

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