自由基清除剂Tempol对小鼠放射性下颌腺损伤防护机制的研究  

Mechanism of the prevention effect of a free radical scavenger, Tempol, on radiation-induced dysfunction in the submandibular gland of mouse

作　　者：王金凤[1] 孙新臣[2] 康亚辉[1] 王忠明[1] 杨曦[2] 蔡晶[3] 张曲[1] 何向锋[3] 马建新[1] 

机构地区：[1]蚌埠医学院附属连云港第二人民医院放疗科,连云港222000 [2]江苏省人民医院放疗科 [3]南通市肿瘤医院放化疗科

出　　处：《中华放射医学与防护杂志》2014年第3期176-179,共4页Chinese Journal of Radiological Medicine and Protection

摘　　要：目的 探讨不同浓度自由基清除剂Tempol （TPL）对C57bl/6小鼠下颌腺放射性损伤的防护作用及作用机制.方法 120只雄性C57bl/6小鼠,随机数字表法分为空白对照组、单纯照射组、25 mg/kg TPL组、200 mg/kg TPL、25 mg/kg TPL＋照射和200 mg/kg TPL＋照射组,共6个组,每组20只.两个联合治疗组在15 Gy照射前10 min腹腔注射给药.观察给药后30 d小鼠存活率、体重和照射后3和30 d小鼠唾液流率及下颌腺组织细胞凋亡及照射后3d下颌腺组织总超氧化物歧化酶活性、总谷胱甘肽和丙二醛（MDA）含量及Bcl-2、Bax、Caspase-3蛋白表达水平.结果 照射后3和30 d单纯照射组小鼠唾液腺流率分别为5.67±1.05,5.27±1.34,与TPL 200 mg/kg＋照射组比较,明显降低,差异有统计学意义（F=226.4,215.3,P＜0.05）,而与TPL25 mg/kg＋照射组比较,差异无统计学意义;此外,TPL 200 mg/kg预处理降低照射后细胞的凋亡和组织MDA的含量（F=175.2,P＜0.05）,增加总谷胱甘肽（GSH）的含量和总超氧化物歧化酶（SOD）的活性（F=244.5、205.5,P＜0.05）,增加Bcl-2蛋白水平,降低Bax和活化Caspase-3蛋白水平.结论 200 mg/kg TPL对C57 bl/6小鼠下颌腺组织具有放射保护作用,其机制可能为减轻组织氧化应激和调节线粒体凋亡信号通路,而25 mg/kg TPL没有此保护作用.Objective To explore the possible mechanism of the prevention effect of Tempol （TPL） on radiation-induced submandibular gland dysfunction using a C57bl/6 mouse model. Methods One-hundred twenty male C57bl/6 mice were randomly divided into six groups： blank control group, radiation group, 25 mg/kg TPL group, 200 mg/kg TPL group, 25 mg/kg TPL ± radiation group and 200 mg/kg TPL ± radiation group. 25 mg/kg and 200 mg/kg TPL was injected to mice enteroeoelia 10 min before 15 Gy X-ray radiation. Survival rate and weight change of the mice were observed 30 d after radiation. Salivary flow rate and mandibular gland apoptosis were detected at 3 and 30 d after radiation. Total superoxide dismutase activity, total glutathione and malondialdehyde content and Bcl-2, Bax, Caspase 3 expression levels were detected at 3 d after radiation. Results Salivary flow rates at 3 and 30 days in the radiation group were 5.67 × 1.05 and 5.27 ± 1.34, lower than that of 200 mg/kg TPL ± radiation group （13.12± 1. 17,13.09 ±2.71） significantly （F=226.4, 215.3, P 〈0.05） but had no significant difference （P 〉0. 05） compared with 25 mg/kg TPL ± radiation group （6.44 ± 1.09,5.48± 1.79）. Pretreatment of mice with 200 mg/kg TPL could reduce radiation induced apoptosis and the content of MDA in tissue but increased the GSH content. The TPL also increased the activity of SOD, the expression of Bcl-2 protein level, but reduced the levels of Bax and cleaved Caspase-3 protein. Conclusions 200 mg/kg TPL could protect C57bl/6 mice salivary glands from radiation injury probably by alleviating oxidative stress and regulating the mitochondrial pathway of apoptosis except 25 mg/kg TPL.

关 键 词：放射性损伤 自由基 氧化应激 下颌腺 

分 类 号：R818[医药卫生—放射医学]