茶多酚和槲皮素对心、脑、肝受自由基损伤的保护作用及与维生素C的作用比较(英文)

Tea Polyphenols and Quercetin Preventing the Heart,Brain and Liver from the Injury by Free Radicals in Comparison with Ascorbic Acid

目的 :比较茶多酚 (TP)、槲皮素 (Que)和维生素C(Vc)的体内外抗氧化作用 ,并分析其构效关系。方法 :采用 4个体外氧化应激模型 :在大鼠的心、脑匀浆和CCl4毒化小鼠肝脏匀浆中用Fenton反应诱导脂质过氧化模型 ,以及H2 O2诱导红细胞溶血模型 ;3个体内模型 :结扎小鼠大脑中动脉 (MCAO)致脑梗塞模型 ,大鼠冠脉缺血再灌注致心律失常模型和CCl4毒化致小鼠肝损伤模型。分别测定了各化合物在这些模型中的抗氧化作用。结果 :在体外 ,Que和TP均可剂量依赖性地抑制Fenton反应导致的大鼠心、脑匀浆和CCl4毒化小鼠肝匀浆中过氧化脂质 (LPO)的生成和H2 O2 诱导的红细胞溶血 :Que的IC50 分别为 :0 4× 10 -4,0 2× 10 -4,0 5× 10 -4,0 3× 10 -4mol/L ;TP的IC50 分别为 :0 7× 10 -4,7 8× 10 -4,1 1×10 -4,0 6× 10 -4mol/L。二者的作用均大大优于Vc(IC50 分别为 110× 10 -4,<0 0 0 1,2 1× 10 -4,2 9× 10 -4mol/L)。在体内 ,2 0mg/kg剂量的Que和TP以及 2 0 0mg/kg剂量的Vc均可有效改善MCAO小鼠的运动功能障碍 ,缩小脑梗塞面积 (ip抑制率分别为 32 % ,2 4 % ,19% ,po抑制率分别为 2 5 % ,2 0 % ,16 % ) ,减少脑组织中LPO的生成及提高GSH PX的活性 ;还可缩小心律失常大鼠的心肌梗塞范围 (抑制率分别为 2

AIM:To compare the antioxidant effects both in vitro and vivo of tea polyphenols (TP),quercetin (Que) and vitamine C (Vc),and analyze the structure-effect relationship.METHOD:In vitro,4 models:Fenton reaction induced lipid peroxidation in homogenates from mouse heart,brain and CCl_(4) damaged liver. H_(2)O_(2)induced hemolysis were applied. In vivo,3 models:the middle cerebral artery occlusion (MCAO)in mice,cardiac arrhythmia by coronary ischemia-reperfusion and CCl_(4) liver damage were tested. Then the antioxidant effects of these compounds were assayed.RESULT: In vitro,the IC_(50) of Que of inhibiting the production of lipid peroxides (LPO) in homogenates from rat heart,brain,and CCl_(4) damaged liver in mice and H_(2)O_(2) induced hemolysis is 0.4×10^(-4),0.2×10^(-4),0.5×10^(-4),0.3×10^(-4) mol/L,separately,while that of TP is 0.7×10^(-4),7.8×10^(-4),1.1×10^(-4),0.6×10^(-4) mol/L,separately. Que and TP exert these effects in an dose-dependant manner and their effects are much superior to Vc (IC_(50) is 110×10^(-4),<0.001,21×10^(-4),2.9×10^(-4) mol/L,separately). In vivo, 20 mg/kg TP and Que and 200 mg/kg Vc ameliorate the motor dysfunction of in MCAO mouse effectively,reduce the cerebral and cardiac infarcted size (inhibitory rate is 20%,25% and 16%,separately),decrease the LPO production (9.36±0.20,9.45±0.21,9.58±0.29 nmol/mg pro.,separately vs 9.87±0.19 nmol/mg pro. in model group) and promote the decline in activity of GSH-PX (24.2±1.8,23.8±1.9,23.6±1.8 μ/mg pro.,separately vs (21.4±2.0 μ/mg pro. in model group) in brain tissue. 20 mg/kg of Que and TP can decrease declined activity of SOD (19.9±1.3,19.7±1.1 μ/mg pro. vs 18.3±1.3 μ/mg pro. in model group) in brain tissue and serum SGPT (inhibitory rate is 38% and 34%) in CCl_(4)damaged liver in mice.CONCLUSION:TP and Que possess better antioxidant effect both in vitro and in vivo,suggesting poly ortho-phenolic hydroxyl group and 4-keto group on α-benzo-pyrone are the structure base of highly effective antioxidants. Vc has better antioxidant effect in vivo than in vitro,which suggests that it may play an indirect role in vivo via other mechanism rather than clearing free radicals directly. The antioxidants possess different selectivity in different models,which suggest that multi-models should be applied for an attention to evaluate an antioxidant for natural sources.