Huang Ling-ling, Pan Chen, Wang Li, Ding Ling, Guo Kun, Wang Hong-zhi, Xu A-Man, Gao Shan
Department of Pharmacology, Basic Medical College, Anhui Medical University, Hefei 230032, China; Cancer Hospital, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China.
Department of Clinical Pharmacy, Lishui People's Hospital, Zhejiang 323000, China.
J Nutr Biochem. 2015 Aug;26(8):841-9. doi: 10.1016/j.jnutbio.2015.03.007. Epub 2015 Apr 24.
Cardiovascular remodeling, as a hallmark of hypertension-induced pathophysiology, causes substantial cardiovascular morbidity and mortality. There is increasing evidence that has demonstrated a broad spectrum of pharmacological and therapeutic benefits of grape seed proanthocyanidins (GSP) against oxidative stress and cardiovascular diseases. In this study, 180- to 200-g SD rats treated with DOCA (120 mg/week sc with 1% NaCl and 0.2% KCl in drinking water) and GSP (150, 240, 384 mg/kg) or amlodipine (ALM) (5 mg/kg) for 4 weeks were recruited. The protective effects of GSP on blood pressure and cardiovascular remodeling in rats with DOCA-salt-induced hypertension were investigated. Our results indicated that DOCA-salt could induce hypertension, cardiovascular remodeling and dysfunction, oxidative stress and the release of endothelin-1 (ET-1) and could increase JNK1/2 and p38MAPK phosphorylation. GSP or ALM treatments significantly improved hypertension, cardiovascular remodeling and dysfunction and oxidative stress, restrained the release of ET-1 and down-regulated the JNK1/2 and p38MAPK phosphorylation. These findings demonstrate that GSP has protective effects against increase of blood pressure induced by DOCA-salt hypertension and cardiovascular remodeling by inhibiting the reactive oxygen species/mitogen-activated protein kinase pathway via restraining the release of ET-1.
心血管重塑作为高血压诱导的病理生理学标志，会导致大量心血管疾病的发病和死亡。越来越多的证据表明，葡萄籽原花青素（GSP）在对抗氧化应激和心血管疾病方面具有广泛的药理和治疗益处。在本研究中，招募了体重180至200克的SD大鼠，用DOCA（每周皮下注射120毫克，饮用水中含1%氯化钠和0.2%氯化钾）和GSP（150、240、384毫克/千克）或氨氯地平（ALM）（5毫克/千克）处理4周。研究了GSP对DOCA-盐诱导的高血压大鼠血压和心血管重塑的保护作用。我们的结果表明，DOCA-盐可诱导高血压、心血管重塑和功能障碍、氧化应激以及内皮素-1（ET-1）的释放，并可增加JNK1/2和p38MAPK的磷酸化。GSP或ALM治疗可显著改善高血压、心血管重塑和功能障碍以及氧化应激，抑制ET-1的释放并下调JNK1/2和p38MAPK的磷酸化。这些发现表明，GSP通过抑制活性氧/丝裂原活化蛋白激酶途径，抑制ET-1的释放，从而对DOCA-盐高血压诱导的血压升高和心血管重塑具有保护作用。
