纳米氧化铈体内代谢特点及其辐射防护作用

Metabolic characteristics and radio-protective function of nano cerium oxide

目的观察纳米氧化铈(nano-CeO_2)在大鼠体内的代谢和分布特点,探讨其辐射防护作用。方法 (1)取18只无特定病原体(SPF)级SD大鼠随机分为3组。实验组和血药浓度组大鼠分别一次性予剂量为1.0 g/kg体质量的nano-CeO_2混悬液灌胃,对照组予等体积蒸馏水灌胃。在不同时间点,血药浓度组大鼠经眼眶静脉取血,采集实验组大鼠尿液与粪便;采集染毒后24.0 h实验组和对照组大鼠的不同器官组织样品,采用电感耦合等离子体-质谱法检测生物样品中的铈水平。(2)将72只SPF级BALB/c小鼠随机分为6组,低、中和高剂量组小鼠分别予剂量为100、300、900 mg/kg体质量的nano-CeO_2混悬液灌胃,阴性对照组、照射对照组和阳性药物对照组小鼠均予等体积蒸馏水灌胃,1次/d;连续灌胃14 d后,除阴性对照组外,其余5组小鼠均给予一次性钴-60γ射线源全身照射,照射剂量为3.5 Gy,剂量率为1 Gy/min,阳性药物对照组照射前30 min予一次性腹腔注射剂量为200 mg/kg体质量的氨磷汀。照射后,各组小鼠继续予相应灌胃处理,1次/d,每组小鼠分别于照射后3和8 d随机抽取6只,采集周围静脉血检测白细胞计数和淋巴细胞计数。结果 (1)染毒后4.0 h,大鼠血液中铈水平达到峰值,染毒后8.0 h尿液和粪便中排泄的铈水平达到峰值。染毒后24.0 h,实验组大鼠大脑中铈水平高于对照组(P<0.05);实验组大鼠中,胸骨、十二指肠、大脑中的铈水平均高于肾脏和心脏(P<0.05),胸腺和肺脏中铈水平均高于肾脏(P<0.05)。(2)小鼠周围血白细胞计数和淋巴细胞计数在染毒处理和染毒时间的交互效应上均无统计学意义(P>0.05)。低、中剂量组小鼠白细胞计数分别低于阴性对照组和阳性药物对照组(P<0.05),高剂量组小鼠白细胞计数分别低于照射对照组、阳性药物对照组和中剂量组(P<0.05),3个剂量组小鼠淋巴细胞计数均低于阳性药物对照组(P<0.05)。结论 nano-CeO_2在体内主要蓄积器官可能为胸骨、十二指肠、大脑、胸腺和肺脏。辐射诱导后,nano-CeO_2具有一定程度的提升周围血白细胞数量的作用。

Objective To observe the in vivo metabolism and distribution characteristics of nano-cerium oxide （nano-CeO2） in rats, and to explore the radio-protective effect of nano-CeO2.Methods i） A total of 18 specific pathogen free （SPF） SD rats were randomly divided into 3 groups.Rats of experiment group and CeO2 blood group were gavaged with 1.0 g/kg body weight （bw） nano-CeO2 suspension.Rats of control group were gavaged with double distilled water （DDW） in equal volume.At different time-points after treatment, venous blood was collected from the rats＇＇ eye socket in CeO2 blood group, meanwhile urine and excrement of rats of experiment group were also collected.Organ and tissue samples of experiment group and control group were collected 24.0 hours after treatment.The concentrations of cerium in biological samples were detected by inductively coupled plasma mass spectrometry.ii） A total of 72 SPF BALB/c mice were randomly divided into 6 groups.Mice of low-, medium-and high-dose groups were gavaged with 100, 300 and 900 mg/kg bw nano-CeO2 suspension respectively.Mice of negative control group, irradiation control group and drug positive control group were gavaged with DDW in equal volume once daily.After 14 days, mice of the other 5 groups were exposed by 60Co γ-rays once with 3.5 Gy （1 Gy/min） except the negative control group.Mice of drug positive control group were given intraperitoneal injection with 200 mg/kg bw amifostine half an hour before irradiation.After exposure, mice were treated by the above gavages once daily.After 3 and 8 days, 6 mice were randomly selected to collect the peripheral blood for the count of white blood cell （WBC） and lymph cell measuring.Results i） The cerium concentration in blood reached peak value in 4.0 hours after exposure of nano-CeO2, and the cerium concentration of urine and excrement reached maximum in 8.0 hours after exposure.After 24.0 hours of exposure, the cerium concentration of brain in experiment group was higher than that of control group （P〈0.05）.Among the experiment group, the cerium concentrations of sternum, duodenum and brain were higher than that of kidney and heart （P〈0.05）, meanwhile the cerium concentrations of thymus and lung were higher than that of kidney （P〈0.05）.ii） There was no statistical difference in interactive effect of WBC count and lymph cell counts between nano-CeO2 exposure ways and time （P〉0.05）.The WBC counts of the low-and medium-dose groups were lower than those of the negative control group and the drug positive control group （P〈0.05）.The WBC count of high-dose group was lower than those of irradiation control group, drug positive control group and medium-dose group （P〈0.05）.The lymph cell counts of the 3 dose groups were lower than that of drug positive control group （P〈0.05）.Conclusion The nano-CeO2 is mainly cumulated in organs such as sternum, duodenum, brain, thymus and lung.After induced by radiation, nano-CeO2 has a certain degree of promotion role in increasing the WBC counts.