白藜芦醇可抑制大鼠非酒精性脂肪性肝病。
Resveratrol inhibits nonalcoholic fatty liver disease in rats.
作者信息
Bujanda Luis, Hijona Elizabeth, Larzabal Mikel, Beraza Marta, Aldazabal Pablo, García-Urkia Nerea, Sarasqueta Cristina, Cosme Angel, Irastorza Belen, González Alberto, Arenas Juan I
机构信息
Department of Gastroenterology, University of Country Basque, Donostia Hospital, Centro de Investigación Biomédica en Enfermedades Hepáticas y Digestivas, San Sebastián, Spain.
出版信息
BMC Gastroenterol. 2008 Sep 9;8:40. doi: 10.1186/1471-230X-8-40.
BACKGROUND
The prevalence of nonalcoholic fatty liver disease (NAFLD) is high. NAFLD is linked to obesity, diabetes mellitus, and hypertriglyceridemia. Approximately 20% of patients with NAFLD will eventually develop cirrhosis. Our purpose was to investigate whether resveratrol decreased hepatic steatosis in an animal model of steatosis, and whether this therapeutic approach resulted in a decrease in tumor necrosis factor alpha (TNF-alpha) production, lipid peroxidation and oxidative stress.
METHODS
Male Wistar CRL: Wi (Han) (225 g) rats were randomized into three groups. A control group (n = 12) was given free access to regular dry rat chow for 4 weeks. The steatosis (n = 12) and resveratrol (n = 12) groups were given free access to feed (a high carbohydrate-fat free modified diet) and water 4 days per week, and fasted for the remaining 3 days for 4 weeks. Rats in the resveratrol group were given resveratrol 10 mg daily by the oral route. All rats were killed at 4 weeks and assessed for fatty infiltration and bacterial translocation. Levels of TNF-alpha in serum, hepatic malondialdehyde (MDA), oxidative stress (superoxide dismutase, glutathione peroxidase, catalase and nitric oxide synthase) and biochemical parameters were measured.
RESULTS
Fat deposition was decreased in the resveratrol group as compared to the steatosis group (Grade 1 vs Grade 3, P < 0.05). TNF-alpha and MDA levels were significantly increased in the steatosis group (TNF-alpha; 33.4 +/- 5.2 vs 26.24 +/- 3.47 pg/ml and MDA; 9.08 +/- 0.8 vs 3.17 +/- 1.45 muM respectively, P < 0.05). This was accompanied by increased superoxide dismutase, glutathione peroxidase and catalase and decreased nitric oxide synthase in the liver of resveratrol group significantly (P < 0.05 vs steatosis group). Bacterial translocation was not found in any of the groups. Glucose levels were decreased in the group of rats given resveratrol (P < 0.05).
CONCLUSION
Resveratrol decreased NAFLD severity in rats. This effect was mediated, at least in part, by TNF-alpha inhibition and antioxidant activities.
背景
非酒精性脂肪性肝病（NAFLD）的患病率很高。NAFLD与肥胖、糖尿病和高甘油三酯血症有关。约20%的NAFLD患者最终会发展为肝硬化。我们的目的是研究白藜芦醇是否能减轻脂肪变性动物模型中的肝脏脂肪变性，以及这种治疗方法是否能降低肿瘤坏死因子α（TNF-α）的产生、脂质过氧化和氧化应激。
方法
将雄性Wistar CRL:Wi（Han）（225 g）大鼠随机分为三组。对照组（n = 12）自由摄取常规干鼠粮4周。脂肪变性组（n = 12）和白藜芦醇组（n = 12）每周4天自由摄取饲料（一种高碳水化合物无脂肪改良饮食）和水，其余3天禁食，共4周。白藜芦醇组大鼠每天经口给予白藜芦醇10 mg。4周后处死所有大鼠，评估脂肪浸润和细菌移位情况。检测血清中TNF-α水平、肝脏丙二醛（MDA）、氧化应激指标（超氧化物歧化酶、谷胱甘肽过氧化物酶、过氧化氢酶和一氧化氮合酶）以及生化参数。
结果
与脂肪变性组相比，白藜芦醇组的脂肪沉积减少（1级对3级，P < 0.05）。脂肪变性组的TNF-α和MDA水平显著升高（TNF-α分别为33.4 ± 5.2对26.24 ± 3.47 pg/ml，MDA分别为9.08 ± 0.8对3.17 ± 1.45 μM，P < 0.05）。白藜芦醇组肝脏中超氧化物歧化酶、谷胱甘肽过氧化物酶和过氧化氢酶增加，一氧化氮合酶减少，差异有统计学意义（与脂肪变性组相比，P < 0.05）。所有组均未发现细菌移位。给予白藜芦醇的大鼠组血糖水平降低（P < 0.05）。
结论
白藜芦醇可减轻大鼠NAFLD的严重程度。这种作用至少部分是通过抑制TNF-α和抗氧化活性介导的。
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