Rashid Sherzad, Idris-Khodja Noureddine, Auger Cyril, Kevers Claire, Pincemail Joël, Alhosin Mahmoud, Boehm Nelly, Oswald-Mammosser Monique, Schini-Kerth Valérie B
1 UMR CNRS 7213 Laboratory of Biophotonics and Pharmacology, Faculty of Pharmacy, University of Strasbourg , Illkirch, France .
2 Plant and Biology Institute, Plant Molecular Biology and Biotechnology Unit, University of Liège , Liège, Belgium .
J Med Food. 2018 Apr;21(4):390-399. doi: 10.1089/jmf.2017.0078. Epub 2018 Mar 23.
Chronic liver diseases with portal hypertension are characterized by a progressive vasodilatation, endothelial dysfunction, and NADPH oxidase-derived vascular oxidative stress, which have been suggested to involve the angiotensin system. This study evaluated the possibility that oral intake of polyphenol-rich blackcurrant juice (PRBJ), a rich natural source of antioxidants, prevents endothelial dysfunction in a rat model of cirrhosis induced by chronic bile duct ligation (CBDL), and, if so, determined the underlying mechanism. Male Wistar rats received either control drinking water or water containing 60 mg/kg gallic acid equivalents of PRBJ for 3 weeks before undergoing surgery with CBDL or sham surgery. After 4 weeks, vascular reactivity was assessed in mesenteric artery rings using organ chambers. Both the acetylcholine-induced nitric oxide (NO)- and endothelium-dependent hyperpolarization (EDH)-mediated relaxations in mesenteric artery rings were significantly reduced in CBDL rats compared to sham rats. An increased level of oxidative stress and expression of NADPH oxidase subunits, COX-2, NOS, and of the vascular angiotensin system are observed in arterial sections in the CBDL group. Chronic intake of PRBJ prevented the CBDL-induced impaired EDH-mediated relaxation, oxidative stress, and expression of the different target proteins in the arterial wall. In addition, PRBJ prevented the CBDL-induced increase in the plasma level of proinflammatory cytokines (interleukin [IL]-1α, monocyte chemotactic protein 1, and tumor necrosis factor α) and the decrease of the anti-inflammatory cytokine, IL-4. Altogether, these observations indicate that regular ingestion of PRBJ prevents the CBDL-induced endothelial dysfunction in the mesenteric artery most likely by normalizing the level of vascular oxidative stress and the angiotensin system.
伴有门静脉高压的慢性肝病的特征是进行性血管舒张、内皮功能障碍以及烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶衍生的血管氧化应激，这些被认为与血管紧张素系统有关。本研究评估了口服富含多酚的黑加仑汁（PRBJ）（一种丰富的抗氧化剂天然来源）能否预防慢性胆管结扎（CBDL）诱导的肝硬化大鼠模型中的内皮功能障碍，若能预防，则确定其潜在机制。雄性Wistar大鼠在接受CBDL手术或假手术前3周，分别饮用对照饮用水或含60mg/kg没食子酸当量PRBJ的水。4周后，使用器官浴槽评估肠系膜动脉环的血管反应性。与假手术大鼠相比，CBDL大鼠肠系膜动脉环中乙酰胆碱诱导的一氧化氮（NO）介导的舒张和内皮依赖性超极化（EDH）介导的舒张均显著降低。在CBDL组的动脉切片中观察到氧化应激水平升高以及NADPH氧化酶亚基、环氧化酶-2（COX-2）、一氧化氮合酶（NOS）和血管紧张素系统的表达增加。长期摄入PRBJ可预防CBDL诱导的EDH介导的舒张受损、氧化应激以及动脉壁中不同靶蛋白的表达。此外，PRBJ可预防CBDL诱导的促炎细胞因子（白细胞介素[IL]-1α、单核细胞趋化蛋白1和肿瘤坏死因子α）血浆水平升高以及抗炎细胞因子IL-4水平降低。总之，这些观察结果表明，定期摄入PRBJ最有可能通过使血管氧化应激水平和血管紧张素系统正常化来预防CBDL诱导的肠系膜动脉内皮功能障碍。
