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