不同剂量X射线对小鼠肝损伤及氧化应激的影响

Impacts of X-rays at varying doses on liver injury and oxidative stress in mice

目的研究不同剂量X射线对小鼠肝损伤及氧化-抗氧化水平的变化。方法将54只8周龄雄性C57BL/6J小鼠分为对照组、2和4 Gy辐照组,每个组又分为照后1、3、7 d组,共分9组,每组6只。照后进行解剖,称量小鼠体重,并计算肝脏指数。检测小鼠肝脏组织病理学变化。检测小鼠外周血细胞计数、天门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)和碱性磷酸酶(ALP),采用分光光度法检测肝脏组织超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量和还原型谷胱甘肽(GSH)含量。结果与对照组相比,照后1、3、7 d小鼠体重显著降低(F=84.03、27.11、25.50,P<0.001),肝脏指数显著升高(F=28.40、17.75,P<0.05)。病理观察出现肝损伤,并呈现剂量-时间效应关系。外周血白细胞、中性粒细胞、淋巴细胞1、3、7 d均显著降低(F=8.42~22.91,P<0.05),且呈现随辐射剂量增加而降低的趋势;4 Gy组照后1 d的AST、ALT水平显著升高(H=7.24、7.82,P<0.05),ALP在照后1、3 d显著升高(F=11.86、9.75,P<0.05),照后1、3、7 d,小鼠MDA和SOD水平呈现先升后降的趋势,GSH水平先降后升;照后1、3、7 d,肝脏MDA水平与组织病理损伤程度呈正相关(r=0.30,P<0.001)。结论不同剂量X射线辐射可影响小鼠肝损伤水平、病理程度、外周血细胞计数、肝功能指标水平和肝脏氧化-抗氧化水平,呈现一定的剂量-时间效应关系。

Objective To investigate the changes in liver injury and oxidative-antioxidant level in mice exposed to X-rays at varying doses.Methods Fifty-four 8-week-old male C57BL/6J mice were divided into three groups,namely the control,2 Gy irradiation,and 4 Gy irradiation groups.Then,each of the groups was further divided by days post-irradiation(i.e.,1,3,and 7 d),and so nine sub-groups(n=6).After irradiation was performed as planned,all the mice were dissected and weighed,and their liver indexes were calculated to determine any histopathological changes in the liver.The peripheral blood cell count and the levels of aspartate aminotransferase(AST),alanine aminotransferase(ALT),and alkaline phosphatase(ALP)were detected.Furthermore,spectrophotometry was also used to determine the superoxide dismutase(SOD)activity,the malondialdehyde(MDA)concentration,and the reduced glutathione(GSH)concentration in liver tissues.Results Compared to the control group,mice undergoing irradiation exhibited a significant reduction in body weight(F=84.03,27.11,25.50,P<0.001),but significantly increased liver indexes(F=28.40,17.75,P<0.001)at 1,3,and 7 d post-irradiation.Pathological observations of these mice revealed liver injury,which proved related to dose and time course.The counts of leukocytes,neutrophils,and lymphocytes in peripheral blood decreased significantly(F=8.42-22.91,P<0.05),trending downward with an increase in the radiation dose.For mice in the 4 Gy irradiation group,their AST and ALT levels increased significantly at 1 d post-irradiation(H=7.24,7.82,P<0.05),and their ALP levels rose notably at 1 and 3 d post-irradiation(F=11.86,9.75,P<0.05).Furthermore,their MDA and SOD levels initially rose and then dropped but their GSH levels exhibited an opposite trend at 1,3,and 7 d post-irradiation.There was a positive correlation between their MDA levels in the liver and the degree of damage to histopathological lesions at 1,3,and 7 d post-irradiation(r=0.30,P<0.001).Conclusions A model for radiation-induced liver injury of mice was preliminarily established in this study.It can be concluded that X-rays at varying doses affect the severity of liver injury,pathological grade,peripheral blood cell count,liver function index,and liver oxidative and antioxidant levels of mice,presenting a certain relationship between dose and time course effects.