西咪替丁对低剂量电离辐射致大鼠氧化应激的保护作用

摘要

Objects To study the protective effects of cimetidine against oxidative stress in rats induced by cumulative low-dose irradiation.Methods Sixty SD rats were randomly divided into 6 groups (10 each):normal control group,model control group,lentinan group [89mg/(kg.d)] and 3 dose groups of cimetidine.After oral administration,all the rats were exposed to γ-ray irradiation 8 hours/day for 12 days,and sacrificed on the 13th day.The activities of superoxide dismutase (SOD),glutathione peroxidase (GPx),catalase (CAT) and the content of malondialdehyde (MDA) in serum,liver,thymus and spleen were determined.By using the superoxide anion radical system,hydroxyl radical system,H2O2 radical system,oxidation system of linoleic acid induced by alkane radical system and diphenyl picryl hydrazinyl radical (DPPH) radical system,the antioxidation activities of cimetidine were detected.Results The activities of SOD in liver and thymus decreased significantly,the GPx activity in serum,liver and spleen decreased significantly and MDA level in serum,liver and spleen increased significantly after 0.3Gy cumulative ionizing radiation.Cimetidine enhanced the activities of antioxidant enzymes in serum and organs,and reduced the MDA level.In a certain concentration range,cimetidine had different scavenging effects onto these radical systems,and showed good performance in hydroxyl radical.Conclusion Cimetidine can effectively ameliorate the oxidative stress from low-dose cumulative irradiation by scavenging free radicals,increase the activity of antioxidant enzymes and reduce the content of lipid peroxidation products,thus presents a potential radio protective effect.%目的 研究西咪替丁对低剂量照射所致大鼠氧化应激损伤的保护作用.方法 研究分体内和体外实验.体内实验以SD大鼠作为研究对象,将60只大鼠按体重随机分为6组,即正常对照组、模型对照组、香菇多糖组(89mg/kg.d)及西咪替丁高中低三个剂量组(n=10).每天于给药后辐照,辐照时间8h,连续12d,第13天处死动物.检测大鼠血清、肝脏、胸腺和脾脏中的超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)及丙二醛(MDA).体外实验:采用超氧阴离子自由基体系、羟基自由基体系、过氧化氢自由基体系、烷基自由基引发的亚油酸氧化体系及二苯代苦味酰肼自由基(DPPH)自由基体系检测西咪替丁清除自由基的能力.结果 体内实验结果显示,给予累积剂量为0.3Gy的低剂量电离辐射照射后,大鼠肝脏、胸腺中抗氧化酶SOD的活力显著下降,血清、肝脏、脾脏中GSH-Px活力明显下降,血清、肝脏、脾脏中MDA含量明显升高.而西咪替丁能不同程度地提升血清和各器官组织中抗氧化酶的活力,降低MDA含量.体外实验结果显示,在一定浓度范围内,西咪替丁对超氧阴离子自由基、羟基自由基、烷基自由基和DPPH自由基均有不同程度的清除作用,对羟基自由基的清除能力最佳.结论 西咪替丁能有效清除自由基,通过增强抗氧化酶活力和降低脂质过氧化产物含量,减轻低剂量累积照射诱导的大鼠氧化应激,显示了较好的辐射防护作用.