纳米二氧化钛与葡萄糖亚急性联合经口染毒对幼年大鼠血糖稳态的影响  

Effect of subacute combined oral exposure of titanium dioxide nanoparticles and glucose on blood glucose homeostasis in young SD rats

作　　者：陈章健[1] 韩硕 郑湃 周淑佩 贾光[1] Chen Zhangjian;Han Shuo;Zheng Pai;Zhou Shupei;Jia Guang(Department of Occupational and Enviromental Health Sciences,School of Public Health,Peking University Health Science Center,Beijing 100191,China;Department of Laboratory Animal Science,Peking University Health Science Center,Beijing 100191,China)

机构地区：[1]北京大学医学部公共卫生学院劳动卫生与环境卫生学系,北京100191 [2]北京大学医学部实验动物科学部,北京100191

出　　处：《卫生研究》2020年第4期527-533,共7页Journal of Hygiene Research

基　　金：国家重点研发计划(No.2017YFC1600204);国家自然科学基金(No.81703257)。

摘　　要：目的探讨纳米二氧化钛(titanium dioxide nanoparticles,TiO2 NPs)与葡萄糖联合染毒对幼年大鼠血糖稳态的影响。方法80只4周龄清洁级SD大鼠按体重随机分为8组(每组10只,雌雄各半)。每天灌胃给予0、2、10和50 mg/kg TiO2 NPs,分别加或不加1.8 g/kg葡萄糖。实验期间每周监测大鼠血糖变化。亚急性染毒30天后进行口服糖耐量试验(oral glucose tolerance test,OGTT),并检测血糖稳态相关指标,包括血液中糖化血清蛋白(glycosylated serum protein,GSP)、糖化血红蛋白(glycosylated hemoglobin,HbA1c)、胰岛素、C肽和胰高血糖素的含量,同时观察大鼠胰腺病理改变。结果TiO2 NPs晶型为锐钛矿,近球形,粒径为(24±5)nm。TiO2 NPs单独染毒对血糖稳态的影响较小,仅雄性大鼠10 mg/kg染毒组第16天时血糖降低,2和50 mg/kg染毒组30天后餐后2 h血糖降低,差异均具有统计学意义(P<0.05)。TiO2 NPs与葡萄糖联合染毒比单独染毒对血糖稳态的影响显著,10 mg/kg染毒组雌性大鼠第9天血糖降低,雄性大鼠30天后糖化血清蛋白下降,餐后30 min和60 min血糖升高及OGTT曲线下面积增加,差异均具有统计学意义(P<0.05)。10 mg/kg TiO2 NPs与葡萄糖联合染毒组雌性大鼠胰岛素降低,雄性大鼠胰岛素降低和胰高血糖素上升,差异均具有统计学意义(P<0.05)。交互作用分析发现,在雄性大鼠中,TiO2 NPs和葡萄糖在影响餐后60 min血糖时存在明显的协同作用(P<0.05)。各实验组大鼠胰腺病理未发现异常。结论亚急性TiO2 NPs和葡萄糖联合经口染毒可以对幼年SD大鼠血糖稳态产生影响,造成暂时性的血糖降低、糖耐量受损以及血糖调节激素适应性变化。效应具有性别差异,雄性大鼠更加敏感。相比TiO2 NPs单独染毒,其与葡萄糖联合染毒可产生更显著的影响。两者在影响餐后血糖上存在明显的协同作用。OBJECTIVE To explore the effect of combined oral exposure of titanium dioxide nanoparticles(TiO2 NPs)and glucose on blood glucose homeostasis in young SD rats.METHODS Eighty 4-week-old young SD rats were randomly divided into 8 groups(10 rats in each group,half male and half female).The rats were exposed to TiO2 NPs through intragastric administration at 0,2,10 and 50 mg/kg with or without 1.8 g/kg glucose daily for 30 days.Blood glucose was monitored weekly during the experiment.Oral glucose tolerance test(OGTT)was carried out after subacute exposure(30 days),and the biomarkers related to blood glucose homeostasis were detected,including the contents of glycosylated serum protein(GSP),glycosylated hemoglobin(HbA1c),insulin,C-peptide and glucagon.At the same time,the pancreatic pathology of rats was observed.RESULTS TiO2 NPs were anatase crystals,closely spherical shape,with an average particle size of(24±5)nm.Exposure of TiO2 NPs alone had little effect on blood glucose homeostasis.Blood glucose decreased on the 16th exposure day at dose of 10 mg/kg TiO2 NPs,and postprandial blood glucose(2 h)decreased after 30 days of TiO2 NPs exposure at doses of 2 and 50 mg/kg in male rats(P<0.05).The combined effect of oral exposure of TiO2 NPs and glucose on blood glucose homeostasis was more obvious than that of TiO2 NPs alone.Blood glucose decreased on the 9th exposure day at dose of 10 mg/kg TiO2 NPs+glucose in female rats,and postprandial blood glucose(2 h)decreased at dose of 2 and 50 mg/kg TiO2 NPs+glucose after 30 days of exposure in male rats(P<0.05).Blood glucose decreased on the 9th day after 10 mg/kg TiO2 NPs+glucose exposure in female rats.The glycosylated serum protein decreased and postprandial blood glucose(30 and 60 min)as well as the area under curve of OGTT increased in male rats after 30 days of exposure(P<0.05).The changes of blood glucose-regulating hormones were only found after the combined exposure of 10 mg/kg TiO2 NPs+glucose for 30 days,including the decrease of insulin in female rats,as well as t

关 键 词：纳米二氧化钛 联合染毒 幼年大鼠葡萄糖稳态 协同作用 

分 类 号：R114[医药卫生—卫生毒理学] R587.1[医药卫生—公共卫生与预防医学]