基于重复测量探讨亚砷酸钠致小鼠肝损伤的研究

职业与健康 ›› 2025, Vol. 41 ›› Issue (10): 1346-1350.

基于重复测量探讨亚砷酸钠致小鼠肝损伤的研究

丁汶萌¹, 黄菲², 卫泽群¹, 吴顺华^1,3

1.新疆医科大学公共卫生学院劳动卫生与环境卫生学教研室,新疆乌鲁木齐 830054;
2.新疆医科大学附属肿瘤医院病理中心,新疆乌鲁木齐 830000;
3.新疆社会主义学院,新疆乌鲁木齐 830063

收稿日期:2025-02-14 修回日期:2025-02-27 出版日期:2025-05-15 发布日期:2025-12-18
通信作者: 吴顺华,教授,E-mail：wushunhua@126.com
作者简介:丁汶萌,男,在读硕士研究生,研究方向为环境与健康。
基金资助:
国家自然科学基金项目（82160650）

Study on liver injury induced by sodium arsenite in mice based on repeated measurements

DING Wenmeng¹, HUANG Fei², WEI Zequn¹, WU Shunhua^1,3

1. Occupational and Environmental Health Teaching and Research Office,School of Public Health,Xinjiang Medical University,Urumqi,Xinjiang 830054,China;
2. Pathology Center,The Affiliated Tumor Hospital of Xinjiang Medical University,Urumqi,Xinjiang 830000,China;
3. Xinjiang Institute of Socialism,Urumqi,Xinjiang 830063,China

Received:2025-02-14 Revised:2025-02-27 Online:2025-05-15 Published:2025-12-18
Contact: WU Shunhua,Professor,E-mail：wushunhua@126.com

摘要/Abstract

摘要： 目的了解砷致小鼠肝损伤中砷暴露浓度与染毒时间的交互作用,为砷致肝损伤的防治提供新的思路。方法以96只SPF级Balb/c雄性小鼠为研究对象,标准体质量,随机数字法分成4组,每组24只。经口饮用含亚砷酸钠的水慢性染毒,其对照、低、中、高浓度组砷染毒浓度分别为0、10、20、40 mg/L。染毒时间9个月,期间染毒3、6、9个月时每组各处理8只小鼠。测量小鼠体质量、肝重以及血清肝功指标丙氨酸氨基转移酶（alanine aminotransferase,ALT）、天冬氨酸氨基转移酶（aspartate aminotransferase,AST）和白蛋白（albumin,ALB）,通过重复测量探讨时间和砷对小鼠肝损伤的影响。Masson染色了解小鼠肝组织纤维化状况。结果不同染毒时间小鼠体质量差异有统计学意义（P<0.05）,染毒6及9个月,不同砷染毒组小鼠肝重、肝脏器系数及lgALT差异均有统计学意义（均P<0.05）,染毒3个月不同砷染毒组小鼠lgAST差异有统计学意义（P<0.05）。重复测量方差分析结果显示,主体内效应分析,时间对小鼠体质量、肝脏器系数、ALB的影响显著（F_组内=287.315、8.620、10.156,均P<0.05）。交互作用分析,小鼠体质量、肝重的砷暴露浓度与染毒时间存在交互作用（F_交互=3.005、3.205,均P<0.05）。主体间效应分析,不同浓度砷染毒小鼠的体质量、肝重、肝脏器系数、lgALT、lgAST比较,差异均有统计学意义（F_组间=8.221、19.084、5.995、11.445、6.290,均P<0.05）。Masson染色结果显示小鼠肝组织纤维化状况与砷暴露浓度和染毒时间呈正相关。结论慢性砷暴露可致小鼠肝损伤、肝纤维化,与砷的暴露浓度和染毒时间密切相关,在体质量、肝重指标中发现砷暴露浓度与染毒时间存在交互作用,为地砷病的防治提供了新的思路。

关键词: 肝损伤, 肝纤维化, 亚砷酸钠, Balb/c小鼠, 重复测量

Abstract: Objective To explore the interactive effects of arsenic exposure concentration and exposure duration on arsenic-induced liver injury in mice,and to provide new ideas for the prevention and treatment of arsenic-induced liver injury. Methods A total of 96 SPF-grade male Balb/c mice with standard body weight were randomly divided into four groups,each consisting of 24 mice,using a random number method. They were chronically exposed to sodium arsenite through oral consumption of water,with arsenic concentrations in the control,low,medium,and high dose groups being 0,10,20,and 40 mg/L,respectively. The exposure period was 9 months,during which 8 mice from each group were treated at 3,6,and 9 months. The body weight and liver weight of the mice were measured,as well as the serum liver function indicators alanine aminotransferase（ALT）,aspartate aminotransferase （AST）,and albumin（ALB）. The effects of time and arsenic on liver injury in mice were investigated through repeated measurements. Masson staining results showed fibrosis in mouse liver tissue. Results There was a statistically significant differences in mouse body weight at different exposure times（P<0.05）. At 6 and 9 months of exposure,there were statistically significant differences in liver weight,liver organ coefficient,and lgALT among mice in different arsenic exposure groups（all P<0.05）. At 3 months of exposure,there was a statistically significant difference in lgAST among mice in different arsenic exposure groups（P<0.05）. Repeated measures ANOVA results showed that in within-subject effect analysis,mice body weight,liver organ coefficient,and ALB showed a time-dependent trends（F_within-group=287.315,8.620,10.156,all P<0.05）. The interaction analysis showed that there was an interaction between arsenic exposure concentration and exposure time of mice body weight and liver weight（F_interaction=3.005,3.205,both P<0.05）. The inter-subject effect analysis showed that there were statistically significant differences in body weight,liver weight,liver organ coefficient,lgALT,and lgAST among mice exposed to different concentrations of arsenic（F_{between-groups}=8.221, 19.084,5.995,11.445,6.290,all P<0.05）. The results of Masson staining showed that the fibrosis status of mouse liver tissue was positively correlated with arsenic exposure concentration and time. Conclusion Chronic arsenic exposure can cause liver injury and fibrosis in mice,which is closely related to the exposure concentration and duration of arsenic,and the interaction between arsenic exposure concentration and time was found in body weight and liver weight indicators,which provides a new thought for the prevention and treatment of endemic arsenism.

Key words: Liver injury, Liver fibrosis, Sodium arsenite, Balb/c mice, Repeated measurements

中图分类号:

R-332

丁汶萌, 黄菲, 卫泽群, 吴顺华. 基于重复测量探讨亚砷酸钠致小鼠肝损伤的研究. [J]职业与健康, 2025, 41(10): 1346-1350.

DING Wenmeng, HUANG Fei, WEI Zequn, WU Shunhua. Study on liver injury induced by sodium arsenite in mice based on repeated measurements. [J]OCCUPATION AND HEALTH, 2025, 41(10): 1346-1350.

参考文献

[1] RAHAMAN M S,RAHMAN M M,MISE N,et al.Environmental arsenic exposure and its contribution to human diseases,toxicity mechanism and management[J].Environ Pollut,2021,289:117940.
[2] BJØRKLUND G,RAHAMAN M S,SHANAIDA M,et al.Natural dietary compounds in the treatment of arsenic toxicity[J].Molecules,2022,27(15):4871.
[3] SU Q,HE Y,PAN H,et al.Toxicity of inorganic arsenic to animals and its treatment strategies[J].Comp Biochem Physiol C Toxicol Pharmacol,2023,271:109654.
[4] HEJAZI S,MOOSAVI M,MOLAVINIA S,et al.Epicatechin ameliorates glucose intolerance and hepatotoxicity in sodium arsenite-treated mice[J].Food Chem Toxicol,2024,192:114950.
[5] LI Z,LI H,WANG D,et al.S-glutathionylation in hepatocytes is involved in arsenic-induced liver fibrosis through activation of the NLRP3 inflammasome,an effect alleviated by NAC[J].Sci Total Environ,2024, 947:174534.
[6] YANG H,MO M,YANG L,et al.A novel quinazoline derivative prevents and treats arsenic-induced liver injury by regulating the expression of rec Q family helicase[J].Int J Mol Sci,2023,24(21):15521.
[7] 孙殿军,高彦辉,刘辉.中国70年地方病防治成效及展望[J].中国公共卫生,2019,35(7):793-796.
[8] 尉红,王正辉,雷延庆,等.改水后10~16年饮水型地方性砷中毒病区居民恶性肿瘤死亡分析[J].中华地方病学杂志,2022,41(1):21-26.
[9] 王楠兰,田继贵,鲁杨,等.氧化苦参碱对慢性染砷大鼠肝损伤的影响[J].环境与健康杂志,2024,41(7):579-583.
[10] 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.
[11] 丁关鑫,黄佳,林勤,等.慢性亚砷酸钠染毒对大鼠肝损伤的研究[J].预防医学,2022,34(9):887-892.
[12] 姚芹,吴顺华,郑玉建,等.亚砷酸钠亚慢性染毒对小鼠肝和脑组织抗氧化水平的影响[J].环境与健康杂志,2009,26(5):401-403.
[13] 王雨洁,马腾,徐诗晴,等.慢性砷暴露所致小鼠胰岛素抵抗及肝脏中miR-155表达的变化[J].环境与健康杂志,2023,40(3):189-194,283.
[14] LV Q,WANG J,YANG H,et al.Didymin ameliorates ulcerative colitis-associated secondary liver damage by facilitating Notch1 degradation[J].Phytomedicine,2024,134:155561.
[15] SOOKOIAN S,PIROLA C J.Liver enzymes,metabolomics and genome-wide association studies:From systems biology to the personalized medicine[J].World J Gastroenterol,2015,21(3):711.
[16] FERRI E,ROSSI P D,SCICHILONE M,et al.Liver enzymes in a cohort of community-dwelling older persons:Focus on sex contribution[J].Nutrients,2022,14(23):4973.
[17] MONDAL S,DAS S,MAHAPATRA P K,et al.Morin encapsulated chitosan nanoparticles(MCNPs) ameliorate arsenic induced liver damage through improvement of the antioxidant system and prevention of apoptosis and inflammation in mice[J].Nanoscale Adv,2022,4(13):2857-2872.
[18] BARANGI S,MEHRI S,MOOSAVI Z,et al.Melatonin attenuates liver injury in arsenic-treated rats:The potential role of the Nrf2/HO-1,apoptosis,and miR-34a/Sirt1/autophagy pathways[J].J Biochem Mol Toxicol,2024,38(1):e23635.
[19] FU X,YANG Y,ZHANG D.Molecular mechanism of albumin in suppressing invasion and metastasis of hepatocellular carcinoma[J].Liver Int,2022,42(3):696-709.
[20] HUANG F,DING G,YUAN Y,et al.PTEN overexpression alters autophagy levels and slows sodium arsenite-induced hepatic stellate cell fibrosis[J].Toxics,2023,11(7):578.