1. School of Public Health, Xinjiang Medical University, Urumqi, Xinjiang 830011, China; 2. Xinjiang Center for Disease Control and Prevention, Urumqi, Xinjiang 830002, China
Abstract：Objective To examine the effect of chronic exposure to sodium arsenite on liver damages in rats. Methods Fifty-six healthy adult SD rats (28 males and 28 females) were randomly divided into 4 groups. Rats in the low-, medium- and high-dose groups were given sodium arsenite solutions at doses of 2, 10 and 50 mg/L for successive 24 weeks, while animals in the control group were given deionized water. The rat body and liver weights were measured and the liver coefficient was estimated. The urine arsenic level was detected using atomic fluorescence spectrometry, and hepatic tissue sections were stained with uranium acetate and lead citrate for morphological observations under an electron microscope. Results The body weights of both male and female rats appeared a tendency towards a rise with the duration of exposure to sodium arsenite (male rat: Wald χ2=3 610.621, P<0.001; female rat: Wald χ2=2 186.217, P<0.001, and there were no significant differences in the rat body weight 24 weeks post-exposure to sodium arsenite in each group, while there was an interaction between time and group (male rat: Wald χ2=15.874, P=0.001; Wald χ2=9.460, P=0.024). There were significant differences in the rat liver weight and liver coefficient in each group (male rat: F=18.964 and 29.968, both P<0.001; female rat: F=11.919 and 15.070, both P<0.001), with the lowest liver weight (10.17±1.15) g and liver coefficient (1.99±0.21)% measured in male rats in the high-dose group, and the highest liver weight (12.91±1.29) g and liver coefficient (4.10±0.56)% in female rats in the high-dose group. The median urine arsenic levels (interquartile range) were 25.60 (30.27), 146.56 (101.06), 1 034.68 (600.06) and 3 796.98 (19 966.89) μg/L in rats in the control, low-dose, medium-dose and high-dose groups, respectively (χ2=50.211, P<0.001), and the urine arsenic level was significantly higher in the medium- and high-dose groups than in the control group (both P<0.001). Hepatic edema was seen in rats in the low- and medium-dose groups, and hepatic edema, focal hepatic cell necrosis, hyperplasia of bile capillaries and peri-bile capillary endolysis were observed in rats in the high-dose group. Conclusions Chronic exposure to arsenic may cause morphological alterations of rat hepatic tissues, and the rat hepatic damage aggravates with the dose of exposure to arsenic.
[1] 狄春红,章云衡,谭晓华,等.砷对巨噬细胞胆固醇流出及ABCA1、ABCG1、SRBI基因表达的影响[J].预防医学,2021,33(10):977-982. DI C H,ZHANG Y H,TAN X H,et al.Arsenic on cholesterol efflux and the expression of ABCA1,ABCG1 and SRBI[J].Prev Med,2021,33(10):977-982. [2] LOOMIS D,GUHA N,HALL A L,et al.Identifying occupational carcinogens:anupdate from the IARC Monographs[J].Occup Environ Med,2018,75(8):593-603. [3] 姚金印,李忠哲,高琳,等.地方性砷中毒所致皮肤损伤及其发病机制研究进展[J].中华地方病学杂志,2018,37(2):160-164. YAO J Y,LI Z Z,GAO L,et al.Skin lesions caused by endemic arsenicosis and pathogenesis:a review[J].Chin J Epidemiol,2018,37(2):160-164. [4] 曾磊,汪永萍.全球两亿人饮用水砷超标[J].生态经济,2018,34(11):6-9. ZENG L,WANG Y P.Arsenic in drinking water of 200 million people worldwide[J].Ecol Econ,2018,34(11):6-9. [5] 窦文静,刘梦瑶,许何丽,等.丹参酮ⅡA磺酸钠对饮水砷暴露诱导小鼠肝脏毒性的拮抗作用[J].环境与健康杂志,2020,37(4):298-301. DOU W J,LIU M Y,XU H L,et al.Antagonistic effects of tanshinone ⅡA sodium sulfonate on liver toxicity induced by arsenic exposure through drinking water[J].J Environ Health,2020,37(4):298-301. [6] 中华人民共和国国家质量监督检验检疫总局.实验动物配合饲料通用质量标准:GB 14924.1—2001[S].北京:中国标准出版社,2002. General Administration of Quality Supervision,Inspection and Quarantine of the People's Republic of China.Laboratory animals-General quality standard for formula feeds:GB 14924.1-2001[S].Beijing:Standards Press of China,2002. [7] 高艳芳,郭有,欧阳璐,等.亚砷酸钠致人肝细胞凋亡及NF-κB信号通路影响的研究[J].毒理学杂志,2016,30(5):346-348,345. GAN Y F,GUO Y,OUYANG L,et al.Effects of sodium arsenite on human hepatocyte apoptosis and NF-κB signaling pathway[J].J Toxicol,2016,30(5):345-348. [8] 张海洋,管小菊,毛广运,等.代谢组学在砷中毒研究的进展和趋势[J].预防医学,2016,28(6):591-594. ZHANG H Y,GUAN X J,MAO G Y,et al.The progress and trend of metabonomics applied in arsenism research[J].Prev Med,2016,28(6):591-594. [9] 高艳芳,邹丽君,郭鲜妮,等.低砷染毒对小鼠的一般作用研究[J].毒理学杂志,2017,31(5):381-383. GAO Y F,ZHOU L J,GUO X N,et al.Study on the general effect of low arsenic exposure on mice[J].J Toxicol,2017,31(5):381-383. [10] 李文波,郎曼,迪力娜尔·买买提,等.亚砷酸钠致成年SD大鼠皮肤损伤的研究[J].医学研究杂志,2021,50(4):55-58. [11] 时明阳,胡倩,毕顶念,等.Dicer1、miR-155表达在亚砷酸钠致大鼠肝损伤中的作用[J].环境与职业医学,2021,38(6):643-648. SHI M Y,HU Q,BI D N,et al.Roles of Dicer1 and miR-155 expression in sodium arsenite-induced liver damage in rats[J].Environ Occup Med,2021,38(6):643-648. [12] 黄佳,张玲,林勤,等.亚砷酸钠染毒对SD大鼠肝脏的损伤作用及血清相关蛋白的表达[J].中国地方病防治杂志,2019,34(4):377-379. HUANG J,ZHANG L,LIN Q,et al.Effects of sodium arsenite on liver injury and expression of serum-associated proteins in SD rats[J].Chin J Control Endemic Dis,2019,34(4):377-379. [13] 高怡,仇玉兰,田凤洁,等.饮水砷暴露大鼠血砷、尿砷和组织砷含量测定分析[J].山西医科大学学报,2011,42(1):33-36. GAO Y,QIU Y L,TIAN F J,et al.Determination and analysis of arsenic in blood,urine and tissues of rats exposed to arsenic in drinking water[J].J Shanxi Med Univ,2011,42(1):33-36. [14] 徐梦伟,任冬燕,孙高峰,等.亚砷酸钠对SD大鼠脏器损伤的实验研究[J].新疆医科大学学报,2018,41(2):193-198. XU M W,REN D Y,SUN G F,et al.Experimental study on organs injury in SD rats induced by sodium arsenite[J].J Xinjiang Med Univ,2018,41(2):193-198. [15] 李述刚,徐上知,牛强,等.三氧化二砷染毒小鼠肝脏中砷甲基化水平与肝脏氧化应激的关系[J].环境卫生学杂志,2015,5(2):89-93,98. LI S G,XU S Z,NIU Q,et al.Relationship between arsenic methylation and oxidative stress in mice liver induced by arsenic trioxide[J].J Environ Hyg,2015,5(2):89-93,98. [16] 高怡,仇玉兰,田凤洁,等.低浓度饮水砷暴露大鼠体内各脏器组织中砷的分布[J].环境与健康杂志,2011,28(2):125-127. GAO Y,QIU Y L,TIAN F J,et al.Organs distribution of arsenic in rat exposed to low-level arsenic through drinking water[J].J Environ Health,2011,28(2):125-127. [17] 李伟,李冰.环境砷暴露对机体损伤的研究进展[J].环境与健康杂志,2016,33(9):836-841. LI W,LI B.Health effects of long-time arsenic exposure:a review of recent studies[J].J Environ Health,2016,33(9):836-841. [18] 孔畅,杨林生,李海蓉,等.内蒙古某饮水型砷中毒病区人群体内砷蓄积与砷代谢的年内变化特征[J].环境化学,2018,37(11):2335-2341. KONG C,YANG L S,LI H R,et al.Annual variations of arsenic accumulation and metabolism in the inhabitants of drinking-water type endemic arsenism area,Inner Mongolia[J].Environ Chem,2018,37(11):2335-2341. [19] WANG J,HU W,YANG H,et al.Arsenic concentrations,diversity and co-occurrence patterns of bacterial and fungal communities in the feces of mice under sub-chronic arsenic exposure through food[J/OL].Environ Int,2020,138[2022-06-18].https://doi.org/10.1016/j.envint.2020.105600. [20] 王晓飞,沈运旺,朱珏,等.长期砷暴露的大鼠尿液代谢组学研究[J].分析化学,2019,47(7):1045-1053. WANG X F,SHEN Y W,ZHU J,et al.Metabolomics study of rat urine with long term arsenic exposure[J].Chin J Anal Chem,2019,47(7):1045-1053. [21] 张露露,吴顺华,李静.亚砷酸钠致大鼠肝纤维化的实验观察[J].环境与健康杂志,2015,32(11):953-957,1035. ZHANG L L,WU S H,LI J.Sodium arsenite caused rat liver fibrosis:an experimental study[J].J Environ Health,2015,32(11):953-957,1035. [22] 曾丹,罗鹏,丁锴,等.亚砷酸钠致大鼠肝功能损伤和肝纤维化形成及其机制探讨[J].环境与健康杂志,2015,32(10):859-862,941. ZENG D,LUO P,DING K,et al.Liver function damage and mechanism of fibrosis induced by sodium arsenite in rats[J].J Environ Health,2015,32(10):859-862,941. [23] 万亭池,程勇,安仙蓉,等.亚慢性砷暴露对大鼠肝脏自噬作用影响[J].中国公共卫生,2021,37(4):686-689. WAN T C,CHENG Y,AN X R,et al.Effects of subchronic arsenic exposure on liver autophagy in rats[J].Chin J Public Health,2021,37(4):686-689.
