Department of Gastroenterology, the Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China.
Braz J Med Biol Res. 2011 Jul;44(7):652-9. doi: 10.1590/s0100-879x2011007500083. Epub 2011 Jul 8.
Silybin, a natural antioxidant, has been traditionally used against a variety of liver ailments. To investigate its effect and the underlying mechanisms of action on non-alcoholic fatty liver in rats, we used 60 4-6-week-old male Sprague-Dawley rats to establish fatty liver models by feeding a high-fat diet for 6 weeks. Hepatic enzyme, serum lipid levels, oxidative production, mitochondrial membrane fluidity, homeostasis model assessment-insulin resistance index (HOMA-IR), gene and protein expression of adiponectin, and resistin were evaluated by biochemical, reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis. Compared with the model group, silybin treatment (26.25 mg·kg(-1)·day(-1), started at the beginning of the protocol) significantly protected against high-fat-induced fatty liver by stabilizing mitochondrial membrane fluidity, reducing serum content of alanine aminotransferase (ALT) from 450 to 304 U/L, decreasing hepatic malondialdehyde (MDA) from 1.24 to 0.93 nmol/mg protein, but increasing superoxide dismutase (SOD) and glutathione (GSH) levels from 8.03 to 9.31 U/mg protein and from 3.65 to 4.52 nmol/mg protein, respectively. Moreover, silybin enhanced the gene and protein expression of adiponectin from 215.95 to 552.40, but inhibited that of resistin from 0.118 to 0.018. Compared to rosiglitazone (0.5 mg·kg(-1)·day(-1), started at the beginning of the protocol), silybin was effective in stabilizing mitochondrial membrane fluidity, reducing SOD as well as ALT, and regulating gene and protein expression of adiponectin (P < 0.05). These results suggest that mitochondrial membrane stabilization, oxidative stress inhibition, as well as improved insulin resistance, may be the essential mechanisms for the hepatoprotective effect of silybin on non-alcoholic fatty liver disease in rats. Silybin was more effective than rosiglitazone in terms of maintaining mitochondrial membrane fluidity and reducing oxidative stress.
水飞蓟素是一种天然抗氧化剂，传统上用于治疗各种肝脏疾病。为了研究其对大鼠非酒精性脂肪肝的作用及其潜在作用机制，我们使用 60 只 4-6 周龄雄性 Sprague-Dawley 大鼠，通过高脂饮食喂养 6 周建立脂肪肝模型。通过生化、逆转录聚合酶链反应（RT-PCR）和 Western blot 分析评估肝酶、血清脂质水平、氧化产物、线粒体膜流动性、稳态模型评估-胰岛素抵抗指数（HOMA-IR）、脂联素和抵抗素的基因和蛋白表达。与模型组相比，水飞蓟素治疗（26.25 mg·kg（-1）·天（-1），从方案开始时开始）通过稳定线粒体膜流动性，显著保护大鼠免受高脂肪诱导的脂肪肝，将血清丙氨酸氨基转移酶（ALT）含量从 450 降至 304 U/L，将肝丙二醛（MDA）从 1.24 降至 0.93 nmol/mg 蛋白，同时增加超氧化物歧化酶（SOD）和谷胱甘肽（GSH）水平，分别从 8.03 增至 9.31 U/mg 蛋白和从 3.65 增至 4.52 nmol/mg 蛋白。此外，水飞蓟素增强了脂联素的基因和蛋白表达，从 215.95 增至 552.40，但抑制了抵抗素的基因和蛋白表达，从 0.118 降至 0.018。与罗格列酮（0.5 mg·kg（-1）·天（-1），从方案开始时开始）相比，水飞蓟素在稳定线粒体膜流动性、降低 SOD 和 ALT 以及调节脂联素的基因和蛋白表达方面均有效（P < 0.05）。这些结果表明，线粒体膜稳定化、抑制氧化应激以及改善胰岛素抵抗可能是水飞蓟素对大鼠非酒精性脂肪性肝病的保肝作用的重要机制。就维持线粒体膜流动性和降低氧化应激而言，水飞蓟素比罗格列酮更有效。
