A Korean herbal medicine, Panax notoginseng, prevents liver fibrosis and hepatic microvascular dysfunction in rats
A Korean herbal medicine, Panax notoginseng, prevents liver fibrosis and hepatic microvascular dysfunction in rats
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DOI：
10.1016/j.lfs.2004.07.030
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发表时间：
2005-02-25
期刊：
影响因子：
6.1
通讯作者：
Kim, CH
中科院分区：
文献类型：
--
作者：
Park, WH;Lee, SK;Kim, CH
研究三七水提物对肝纤维化的预防作用。（Arialiaceae）根（PNS）对褐毛大鼠（LEC大鼠）的影响。LEC大鼠分为三组：A组饲喂基础日粮（BD）；B， BD加1% PNS饲喂；Q组饲喂BD + 0.005%番茄红素作为对照。所有大鼠于26周龄处死。A组纤维化面积占总面积的比例为1.46 +/- 0.47，B组为0.83 +/- 0.10 (P = 0.0030, B vs A)， C组为0.91 +/- 0.45 （P = 0.0035, C vs A）。A组α - sma染色面积占总染色面积的百分比为0.56 +/- 0.34，B组为0.15 +/- 0.02 (P = 0.0016, B vs. A)， C组为0.11 +/- 0.01 （P = 0.0025, C vs. A）。B组肝脏丙二醛（MDA）含量低于C组（P = 0.007）。C组大鼠肝脏铁离子浓度低于A组（P = 0.0053）。因此，PNS通过减少脂质过氧化物的生成来抑制纤维生成。PNS预防成纤维作用的机制可能是抑制星状细胞活性。本研究的第二个目的是确定PNS是否影响肠缺血再灌注（I/R）引起的肝脏微血管功能障碍，因为肠缺血再灌注（I/R）引起肝脏微血管功能障碍，并探讨一氧化氮（NO）的作用。雄性Wistar大鼠肠缺血30 min，再灌注60 min。采用活体显微镜监测非灌注窦状体（NPS）数量。在另一组实验中，大鼠灌胃PNS (1 g/kg / d) 7天。在一些实验中，给予地塞米松（ST）（每天静脉注射2mg /kg）。在对照大鼠中，肠道I/R引起NPS数量增加，血浆tnf - α和ALT活性增加，PNS预处理减轻了这些变化。预处理NO合酶抑制剂可降低PNS对NPS和血浆tnf - α水平升高的保护作用，但不影响其对血浆ALT活性升高的影响。PNS预处理可提高血浆亚硝酸盐/硝酸盐水平。NO合成酶抑制剂预处理不影响st的作用。这些结果表明，PNS通过增强NO的产生，在早期减弱肠道I/R诱导的肝脏微血管功能障碍和炎症反应，如tnf - α的产生，并通过其抗炎作用减弱肝细胞的连续损伤。(C) 2005爱思唯尔公司版权所有。
We assessed the prevention of hepatic fibrogenesis by water-extract of Panax notoginseng Buck F.H. Chen. (Arialiaceae) root (PNS) in Long-Evans rats with cinnamon coat color (LEC rats). LEC rats were divided into three groups A, fed on a basal diet (BD); B, fed on BD plus 1% PNS; and Q, fed on BD plus 0.005% lycopene as a control. All rats were sacrificed at 26 weeks of age. The percentage of the total area involved by fibrosis was 1.46 +/- 0.47 in group A, 0.83 +/- 0.10 in B (P = 0.0030, B vs A) and 0.91 +/- 0.45 in C (P 0.0035, C vs. A). The percentage of the total area that was stained for alpha-SMA was 0.56 +/- 0.34 in group A, 0.15 +/- 0.02 in B (P = 0.0016, B vs. A and 0.11 +/- 0.01 in C (P = 0.0025, C vs. A. In group B, malondialdehyde (MDA) in the liver was lower than in group C (P = 0.007). In group C, the concentration of iron in the liver was lower than in group A (P = 0.0053). Thus, PNS suppressed fibrogenesis through reduced generation of lipid peroxides. The mechanisms of this preventive effect of fibrogenesis with PNS were suggested to inhibit the stellate cell activity. Second objective of this study was to determine whether PNS affects hepatic microvascular dysfunction elicited by gut ischemia and reperfusion (I/R), since gut I/R causes hepatic microvascular dysfunction, and to investigate the role of nitric oxide (NO). Male Wistar rats were exposed to 30 min of gut ischemia followed by 60 min of reperfusion. Intravital microscopy was used to monitor the number of non-perfused sinusoids (NPS). In another set of experiments, PNS (1 g/kg per day intragastrically) was administered to rats for 7 days. In some experiments, dexamethasone (ST) (2 mg/kg per day intravenously) was administered. In control rats, gut I/R elicited increases in the number of NPS, and plasma TNF-alpha and ALT activities, and these changes were mitigated by the pretreatment with PNS. Pretreatment with an NO synthase inhibitor diminished the protective effects of PNS on the increase in NPS and plasma TNF-alpha levels, but not its effect on the increase in plasma ALT activities. Pretreatment with PNS increased plasma nitrite/nitrate levels. The responses caused by gut I/R were attenuated by the pretreatment with ST. Pretreatment with an NO synthase inhibitor did not affect the effect of ST. These results suggest that PNS attenuates the gut I/R-induced hepatic microvascular dysfunction and inflammatory responses such as TNF-alpha production in the early phase via enhancement of NO production, and sequential hepatocellular damage via its anti-inflammatory effect. (C) 2005 Elsevier Inc. All rights reserved.