CAJ | 학술논문

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.
목적 탐토불동농도자유기청제제Tempol (TPL)대C57bl/6소서하합선방사성손상적방호작용급작용궤제.방법 120지웅성C57bl/6소서,수궤수자표법분위공백대조조、단순조사조、25 mg/kg TPL조、200 mg/kg TPL、25 mg/kg TPL+조사화200 mg/kg TPL+조사조,공6개조,매조20지.량개연합치료조재15 Gy조사전10 min복강주사급약.관찰급약후30 d소서존활솔、체중화조사후3화30 d소서타액류솔급하합선조직세포조망급조사후3d하합선조직총초양화물기화매활성、총곡광감태화병이철(MDA)함량급Bcl-2、Bax、Caspase-3단백표체수평.결과 조사후3화30 d단순조사조소서타액선류솔분별위5.67±1.05,5.27±1.34,여TPL 200 mg/kg+조사조비교,명현강저,차이유통계학의의(F=226.4,215.3,P＜0.05),이여TPL25 mg/kg+조사조비교,차이무통계학의의;차외,TPL 200 mg/kg예처리강저조사후세포적조망화조직MDA적함량(F=175.2,P＜0.05),증가총곡광감태(GSH)적함량화총초양화물기화매(SOD)적활성(F=244.5、205.5,P＜0.05),증가Bcl-2단백수평,강저Bax화활화Caspase-3단백수평.결론 200 mg/kg TPL대C57 bl/6소서하합선조직구유방사보호작용,기궤제가능위감경조직양화응격화조절선립체조망신호통로,이25 mg/kg TPL몰유차보호작용.
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 enterocoelia 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.