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.
Wei Sheng Yan Jiu. 2020 Jul;49(4):527-533. doi: 10.19813/j.cnki.weishengyanjiu.2020.04.001.
To explore the effect of combined oral exposure of titanium dioxide nanoparticles(TiO_2 NPs) and glucose on blood glucose homeostasis in young SD rats.
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 TiO_2 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(HbA1 c), insulin, C-peptide and glucagon. At the same time, the pancreatic pathology of rats was observed.
TiO_2 NPs were anatase crystals, closely spherical shape, with an average particle size of(24±5)nm. Exposure of TiO_2 NPs alone had little effect on blood glucose homeostasis. Blood glucose decreased on the 16 th exposure day at dose of 10 mg/kg TiO_2 NPs, and postprandial blood glucose(2 h) decreased after 30 days of TiO_2 NPs exposure at doses of 2 and 50 mg/kg in male rats(P<0. 05). The combined effect of oral exposure of TiO_2 NPs and glucose on blood glucose homeostasis was more obvious than that of TiO_2 NPs alone. Blood glucose decreased on the 9 th exposure day at dose of 10 mg/kg TiO_2 NPs+glucose in female rats, and postprandial blood glucose(2 h) decreased at dose of 2 and 50 mg/kg TiO_2 NPs+glucose after 30 days of exposure in male rats(P<0. 05). Blood glucose decreased on the 9 th day after 10 mg/kg TiO_2 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 TiO_2 NPs+glucose for 30 days, including the decrease of insulin in female rats, as well as the decrease of insulin and the increase of glucagon in male rats(P<0. 05). The interaction analysis showed that TiO_2 NPs and glucose had significant synergistic effect on postprandial blood glucose(60 min) in male rats(P<0. 05). No abnormality was found in the pathological observation of pancreas in rats of experimental groups.
Subacute combined oral exposure of TiO_2 NPs and glucose could affect the blood glucose homeostasis of young SD rats, resultsing in temporary hypoglycemia and impaired glucose tolerance, as well as adaptive changes of blood glucose-regulating hormones. The male rats were more sensitive. Compared with the exposure of TiO_2 NPs alone, the combined exposure of TiO_2 NPs and glucose induced more significant effects. Significant synergistic effect between them occurred on postprandial blood glucose.
探讨二氧化钛纳米颗粒（TiO₂ NPs）与葡萄糖联合经口暴露对幼年SD大鼠血糖稳态的影响。
将80只4周龄的幼年SD大鼠随机分为8组（每组10只，雌雄各半）。大鼠每天经口给予0、2、10和50 mg/kg的TiO₂ NPs，同时分别给予或不给予1.8 g/kg葡萄糖，连续30天。实验期间每周监测血糖。亚急性暴露（30天）后进行口服葡萄糖耐量试验（OGTT），并检测与血糖稳态相关的生物标志物，包括糖化血清蛋白（GSP）、糖化血红蛋白（HbA1c）、胰岛素、C肽和胰高血糖素的含量。同时，观察大鼠胰腺病理情况。
TiO₂ NPs为锐钛矿晶体，呈近球形，平均粒径为（24±5）nm。单独暴露TiO₂ NPs对血糖稳态影响较小。在10 mg/kg TiO₂ NPs剂量下，第16天暴露时血糖降低；在2和50 mg/kg TiO₂ NPs剂量下，雄性大鼠暴露30天后餐后血糖（2小时）降低（P<0.05）。TiO₂ NPs与葡萄糖联合经口暴露对血糖稳态的影响比单独暴露TiO₂ NPs更明显。在雌性大鼠中，10 mg/kg TiO₂ NPs+葡萄糖剂量下，第9天暴露时血糖降低；在雄性大鼠中，2和50 mg/kg TiO₂ NPs+葡萄糖剂量下，暴露30天后餐后血糖（2小时）降低（P<0.05）。雌性大鼠在10 mg/kg TiO₂ NPs+葡萄糖暴露9天后血糖降低。雄性大鼠暴露30天后，糖化血清蛋白降低，餐后血糖（30和60分钟）以及OGTT曲线下面积增加（P<0.05）。仅在10 mg/kg TiO₂ NPs+葡萄糖联合暴露30天后发现血糖调节激素发生变化，包括雌性大鼠胰岛素降低，以及雄性大鼠胰岛素降低和胰高血糖素升高（P<0.05）。交互作用分析显示TiO₂ NPs与葡萄糖对雄性大鼠餐后血糖（60分钟）有显著协同作用（P<0.05）。实验组大鼠胰腺病理观察未见异常。
TiO₂ NPs与葡萄糖亚急性联合经口暴露可影响幼年SD大鼠的血糖稳态，导致暂时低血糖和糖耐量受损，以及血糖调节激素的适应性变化。雄性大鼠更敏感。与单独暴露TiO₂ NPs相比，TiO₂ NPs与葡萄糖联合暴露诱导的效应更显著。它们在餐后血糖上存在显著协同作用。
