Wang Yujue, Huang Mengwei, Yang Xiaofeng, Yang Zhongmei, Li Lingling, Mei Jie
Department of Obstetrics and Gynecology, Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital, Chengdu City, Sichuan 610072, China.
Department of Obstetrics and Gynecology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646099, China.
Korean J Physiol Pharmacol. 2018 Jul;22(4):409-417. doi: 10.4196/kjpp.2018.22.4.409. Epub 2018 Jun 25.
Pre-eclampsia (PE) is a pregnancy disorder that is characterised by severe hypertension and increased risks of foetal and maternal mortality. The aetiology of PE not completely understood; however, maternal nutrition and oxidative stress play important roles in the development of hypertension. The treatment options for PE are currently limited to anti-hypertensive drugs. Punicalagin, a polyphenol present in pomegranate juice, has a range of bioactive properties. The effects of supplementation with punicalagin on angiogenesis and oxidative stress in pregnant rats with induced hypertension were investigated. The pregnant rats were randomly divided into five experimental groups (=12 per group). Hypertension was induced using an oral dose of NG-nitro-L-arginine methyl ester (L-NAME, 50 mg/kg/day) on days 14-19 of pregnancy. Punicalagin (25, 50 or 100 mg/kg) was given orally on days 14-21 of pregnancy. Punicalagin treatment at the tested doses significantly reduced diastolic, systolic, and mean arterial blood pressure in L-NAME treated rats from day 14. Punicalagin also restored angiogenic balance by increasing the expression of vascular endothelial growth factor and downregulating vascular endothelial growth factor receptor-1/fms-like tyrosine kinase-1. Punicalagin, significantly increased the placental nitric oxide levels as compared to PE group. The increased levels of oxidative stress in rats with PE were markedly decreased by treatment with punicalagin. Punicalagin at the tested doses markedly (p<0.05) enhanced the placental antioxidant capacity in L-NAME-treated rats. The raised catalase activity observed following L-NAME induction was significantly (p<0.05) and restored to normal activity levels in punicalagin treatment. Further, 100 mg dose of punicalagin exhibited higher protective effects as compared to lower doses of 25 and 50 mg. This study shows that supplementation with punicalagin decreased blood pressure and oxidative stress and restored angiogenic balance in pregnant rats with induced PE.
子痫前期（PE）是一种妊娠疾病，其特征为严重高血压以及胎儿和孕产妇死亡风险增加。PE的病因尚未完全明确；然而，母体营养和氧化应激在高血压的发展中起着重要作用。目前，PE的治疗选择仅限于抗高血压药物。石榴汁中的多酚成分——石榴皮素具有一系列生物活性特性。本研究调查了石榴皮素对诱导高血压的妊娠大鼠血管生成和氧化应激的影响。将妊娠大鼠随机分为五个实验组（每组n = 12）。在妊娠第14 - 19天，通过口服剂量的NG-硝基-L-精氨酸甲酯（L-NAME，50 mg/kg/天）诱导高血压。在妊娠第14 - 21天，口服给予石榴皮素（25、50或100 mg/kg）。从第14天起，经测试剂量的石榴皮素治疗可显著降低L-NAME处理大鼠的舒张压、收缩压和平均动脉血压。石榴皮素还通过增加血管内皮生长因子的表达并下调血管内皮生长因子受体-1/类fms酪氨酸激酶-1来恢复血管生成平衡。与PE组相比，石榴皮素显著提高了胎盘一氧化氮水平。用石榴皮素治疗可显著降低PE大鼠氧化应激水平的升高。经测试剂量的石榴皮素显著（p<0.05）增强了L-NAME处理大鼠的胎盘抗氧化能力。L-NAME诱导后观察到的过氧化氢酶活性升高在石榴皮素治疗中显著（p<0.05）恢复到正常活性水平。此外，与较低剂量的25 mg和50 mg相比，100 mg剂量的石榴皮素表现出更高的保护作用。本研究表明，补充石榴皮素可降低诱导PE的妊娠大鼠的血压和氧化应激，并恢复血管生成平衡。
