Resveratrol Inhibits Dimethylnitrosamine-Induced Hepatic Fibrosis in Rats
Resveratrol Inhibits Dimethylnitrosamine-Induced Hepatic Fibrosis in Rats
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DOI：
10.1007/s12272-010-0616-4
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发表时间：
2010-06-01
影响因子：
6.7
通讯作者：
Moon, Jeon-Ok
中科院分区：
文献类型：
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作者：
Lee, Eun-Sil;Shin, Mi-Ok;Moon, Jeon-Ok
白藜芦醇是一种在葡萄和红葡萄酒中发现的植物抗毒素，据报道具有广泛的药理作用。本研究观察白藜芦醇对二甲基亚硝胺(DMN)所致大鼠肝损伤的保护作用。口服白藜芦醇(20 mg/kg/d，连续4周)可显著阻止DMN所致小鼠体重和肝脏重量的减轻，并能抑制血清丙氨酸转氨酶、天冬氨酸转氨酶、碱性磷酸酶和胆红素水平的升高。由于其抗氧化作用，白藜芦醇还可提高血清白蛋白和肝脏谷胱甘肽水平，降低肝脏丙二醛水平。此外，白藜芦醇处理组大鼠肝组织羟脯氨酸含量明显低于DMN组，这一结果与肝组织天狼星红染色的I型胶原基因表达减少及肝组织学观察结果一致。通过α-平滑肌肌动蛋白染色评估的肝星状细胞活性的减少和转化生长因子-β1mRNA表达的减少与白藜芦醇治疗有关。综上所述，白藜芦醇在体内对DMN诱导的肝损伤具有保肝和抗纤维化作用，提示白藜芦醇可能对预防肝纤维化的发展有一定的作用。
Resveratrol, a phytoalexin found in grapes and red wines, has been reported to exhibit a wide range of pharmacological properties. In this study, we investigated the protective effect of resveratrol on hepatic injury induced by dimethylnitrosamine (DMN) in rats. Oral administration of resveratrol (20 mg/kg daily for 4 weeks) remarkably prevented the DMN-induced loss in body and liver weight, and inhibited the elevation of serum alanine transaminase, aspartate transaminase, alkaline phosphatase and bilirubin levels. Resveratrol also increased serum albumin and hepatic glutathione levels and reduced the hepatic level of malondialdehyde due to its antioxidant effect. Furthermore, DMN-induced elevation of hydroxyproline content was reduced in the resveratrol treated rats, the result of which was consistent with the reduction in type I collagen mRNA expression and the histological analysis of liver tissue stained with Sirius red. The reduction in hepatic stellate cell activation, as assessed by alpha-smooth muscle actin staining, and the reduction in transforming growth factor-beta 1 mRNA expression were associated with resveratrol treatment. In conclusion, resveratrol exhibited in vivo hepatoprotective and antifibrogenic effects against DMN-induced liver injury, suggesting that resveratrol may be useful in the prevention of the development of hepatic fibrosis.