【摘要】 目的探讨12β-羟基藜芦酰棋盘花胺(12β-hydroxylveratroylzygadenine,Vog)引起小鼠小脑和大脑皮层组织DNA损伤的影响。方法取132只雄性昆明种小鼠,随机分为空白组,Vog高(2.50μmol/kg)、低剂量组(0.25μmol/kg),给药7 d。采用彗星实验检测小脑和大脑皮层DNA损伤及修复情况;酶联免疫法检测8-羟基脱氧鸟苷(8-OHd G)、醌氧化还原酶(NQO1)含有量;比色法测定小脑和大脑皮层活性氧自由基(ROS)、丙二醛(MDA)、一氧化氮(NO)含有量和总超氧化物歧化酶(T-SOD)、谷胱甘肽过氧化物酶(GSH-Px)活力;RT-PCR检测小脑和大脑皮层8-羟基鸟嘌呤DNA糖苷酶(Ogg1)和血红素加氧酶-1(Ho-1)mRNA表达。结果 Vog明显提高小鼠小脑和大脑皮层MDA、ROS、NO以及尿液中8-OHd G含有量,降低GSH-Px和T-SOD活力,以及NQO1含有量,上调Ogg1表达。停药后第3天DNA修复接近正常水平,8-OHd G含有量接近正常水平。结论 Vog可能引起氧化应激,导致DNA损伤。Vog同时上调Ogg1表达,为抗氧化防御状态和DNA修复系统的代偿性调节。更多还原

【Abstract】 AIM To investigate DNA damage of 12β-hydroxylveratroylzygadenine( Vog) to mouse cerebellum and cerebral cortex. METHODS One hundred and thirty-two male mice were randomly divided into the control group,Vog high-( 2. 50 μmol / kg) and Vog low-dose groups( 0. 25 μmol / kg). Comet assay was used to detect DNA damage and repair of mouse cerebellum and cerebral cortex. Their levels of 8-hydroxy- deoxyguanosine( 8-OHd G) and quinone oxidoreductase( NQO1) were determined by enzyme-linked immunosorbent assay. The colorimetry was applied to measuring reactive oxygen species( ROS),methane dicarboxylic aldehyde( MDA),nitric oxide( NO),total superoxide dismutase( T-SOD) and glutathione peroxidase( GSH-Px). RT-PCR was performed to examine the levels of 8-hydroxyl-guanine DNA glycosylase( Ogg1) and hemeoxygenase-1( Ho-1) mRNA.RESULTS Vog could significantly increase the levels of MDA,ROS,NO and 8-OHd G; reduce NQO1 level and the vitality of GSH-Px and T-SOD; and increase Ogg1 mRNA expressions in mouse cerebellum and cerebral cortex.Meanwhile,DNA damage was repaired and the content of 8-OHd G was restored close to the normal level on the third day after Vog withdrawn. CONCLUSION Vog may cause oxidative stress and consequently lead to DNA damage; at the same time it also raises the expression of Ogg1 mRNA as a compensatory adjustment to the antioxidant defense status and DNA repair systems.更多还原