大豆异黄酮对四氯化碳致小鼠肝脏氧化应激和DNA损伤的干预作用

Intervention Effect of Soy Isoflavones on Hepatic Oxidative Stress and DNA Damage Induced by Carbon Tetrachloride in Mice

研究大豆异黄酮对四氯化碳(carbon tetrachloride,CCl4)诱发的急性肝损伤小鼠肝脏氧化应激和DNA损伤的干预作用。将50只小鼠随机分为5组,即正常组、模型组、联苯双脂组及大豆异黄酮高、低剂量组。每日给药1次,连续7 d。实验末期,除正常组外,其余组小鼠腹腔注射CCl4建立急性肝损伤模型。分光光度法检测血清谷丙转氨酶、谷草转氨酶、碱性磷酸酶活性、白蛋白含量,肝脏超氧化物歧化酶、谷胱甘肽过氧化物酶、过氧化氢酶活性及还原型谷胱甘肽、丙二醛含量,蛋白印迹法检测血红素加氧酶-1蛋白表达,电泳法检测小鼠肝细胞DNA损伤情况。结果表明:大豆异黄酮明显降低CCl4致急性肝损伤小鼠血清谷丙转氨酶、谷草转氨酶、碱性磷酸酶活性;降低肝组织丙二醛水平;升高肝组织总超氧化物歧化酶、Mn-超氧化物歧化酶、谷胱甘肽过氧化物酶、过氧化氢酶活性和还原型谷胱甘肽水平;升高肝线粒体Na+-K+-ATP酶和Ca2+-Mg2+-ATP酶活性;上调肝组织血红素加氧酶-1蛋白表达;并减少肝细胞DNA损伤程度。提示,大豆异黄酮对CCl4致急性肝损伤具有保护作用,其机制可能与其降低肝组织氧化应激和DNA损伤作用有关。

The intervention effect of soy isoflavones （ISOF） on oxidative stress and DNA damage in a mouse model ofacute liver injury induced by carbon tetrachloride （CCl4） was investigated. Fifty mice were randomly divided into 5 groupsincluding normal control, model control, bifendate （BFD）, high-dose ISOF and low-dose ISOF groups. Animals were treatedonce daily for 7 days. At the end of the experiments, CCl4 was injected intraperitoneally to the mice from four groups exceptthe normal control group. Then, alanine aminotransferase （ALT）, aspartate aminotransferase （AST）, alkaline phosphatase（ALP）, albumin （ALB）, superoxide dismutase （SOD）, catalase （CAT）, glutathione peroxidase （GSH-Px）, Na＋-K＋-ATPase,Ca2＋-Mg2＋-ATPase, reduced glutathione （GSH） and malondialdehyde （MDA） were determined spectrometrically, and protein expression of heme oxygenase-1 （HO-1） was assayed through western blotting, and DNA damage was evaluatedby electrophoresis. The results showed that the administration of ISOF reduced serum activities of ALT, AST and ALP GSH-Px;decrease MDA content in liver; increased total SOD, Mn-SOD, GSH-Px and CAT activities and GSH level in liver; enhanced Na＋-K＋-ATPase and Ca2＋-Mg2＋-ATPase activities in liver mitochondria; up-regulated the expression of HO-1 protein; and reduced DNA damage of hepatocytes in mice with acute liver injury. Therefore, ISOF exerts a protective function on acute liver injuryinduced by CCl4in mice, probably via reducing oxidative stress and DNA damage in liver tissue.