机构地区:[1]温州医科大学附属第一医院急诊医学中心,325000
出 处:《中华劳动卫生职业病杂志》2014年第5期352-356,共5页Chinese Journal of Industrial Hygiene and Occupational Diseases
基 金:浙江省“十二五”重点学科建设计划;浙江省医学创新学科(11-CX26);浙江省中医药重点学科(2012-XK-A28)
摘 要:目的 探讨姜黄素对急性百草枯中毒大鼠肝组织氧化应激损伤的疗效和作用机制.方法 60只大鼠随机分为正常对照组(生理盐水),姜黄素对照组(姜黄素50 mg/kg),百草枯染毒组(百草枯100 mg/kg),姜黄素干预组(百草枯染毒后15 min、24 h、48 h,腹腔注射姜黄素50 mg/kg),每组15只.不同处理后1、3、7 d取肝组织,化学比色法检测肝组织匀浆丙二醛(MDA)含量,超氧化物歧化酶(SOD),过氧化氢酶(CAT)活力;双抗夹心酶联免疫吸附法(ELISA)检测血红素氧合酶-1(HO-1)、醌氧化还原酶-1(NQO-1)活力;反转录-聚合酶链式反应(RT-PCR)法检测核因子E2相关因子2转录因子(Nrf2)mRNA表达,蛋白免疫印迹法(Western blot)检测Nrf2蛋白表达,光学显微镜下观察肝组织病理变化.结果 与正常对照组比较,姜黄素对照组各项观察指标无明显变化,差异均无统计学意义(P〉0.05).与正常对照组比较,百草枯染毒组和姜黄素干预组MDA含量均升高,SOD、CAT活力均降低,HO-1 、NQO-1活力升高,Nrf2 mRNA和蛋白表达均升高,除第7天百草枯染毒组HO-1活力外,差异均有统计学意义(P<0.05).与同时间点百草枯染毒组比较,姜黄素干预组在第1、3、7天,MDA含量明显降低,SOD、CAT、HO-1、NQO-1活力明显升高,Nrf2 mRNA和蛋白表达明显升高,差异均有统计学意义(P<0.05).光学显微镜下可见,百草枯染毒组大鼠肝组织在染毒后第3天,病理损害最严重,各个时间点姜黄素干预组病理损害都较同时间点百草枯染毒组有所减轻.结论 姜黄素通过诱导Nrf2的表达,升高HO-1 、NQO-1、SOD、CAT活力,降低MDA含量,提高肝组织细胞的抗氧化应激能力,对急性百草枯所致的肝损伤有一定的保护作用.Objective To investigate the effect of curcumin on liver injury in rats induced by paraquatmediated oxidative stress and the mechanism underlying its effect.Methods Sixty rats were randomly divided into 4 groups:control group,curcumin control group (curcumin 50 mg/kg),paraquat group (2% paraquat solution 100 mg/kg),and curcumin intervention group (curcumin 50 mg/kg at 15 min,24 h,or 48 h after paraquat exposure).On days 1,3,or 7 after paraquat administration,and liver tissue was collected thereafter.The content ofmalonaldehyde (MDA) and the activities ofsuperoxide dismutase activity (SOD) and catalase (CAT) in the liver tissue were determined by chemical colorimetry.The activities of heme oxygenase 1 (HO-1) and quiuone oxidoreductase 1 (NQO-1) in the liver tissue were determined by ELISA.The mRNA and protein levels of NF-E2-related factor 2 (Nrf2) were determined by RT-PCR and Western blot,respectively.The pathological changes of liver tissue were examined by optical microscopy.Results No significant change was observed between the control group and the curcumin control group in any examination of this study (P >0.05).Both paraquat group and curcumin intervention group showed increase in MDA content,decreases in SOD and CAT activities,increases in HO-1 and NQO-1 activities,and increases in the protein and mRNA levels of Nrf2,in comparison with the control group (P<0.05 for all except HO-1 activity in paraquat group on day 7).In comparison with the parquet group on the same day,the curcumin intervention group showed decrease in MDA content,increases in the activities of SOD,CAT,HO-1,and NQO-1,and increases in the mRNA and protein levels of Nrf2 on days 1,3,and 7 (P<0.05).The pathological examination revealed that the damage of liver tissue in the paraquat group was the most serious on the 3rd day after paraquat exposure,and the damage was consistently alleviated by curcumin intervention on days 1,3,and 7,as compared with the paraquat group.Conclusion Oxidat
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