Abstract: Objective To explore the dynamic expressions of serum miR-122 and miR-155 during the liver injury induced by valproate (VPA) in young mice and their relationship with liver injury. Methods Kunming mice aged 4 weeks were randomly divided into control groups (n=30) and experimental groups (n=56) according to random number table method. Seven experimental groups were given VPA 375 mg·kg-1·d-1 for 1 day, 3 days, 5 days, 7 days, 14 days, 21 days and 28 days consecutively. While five control groups were given 1 mL normal saline daily for 1 day, 7 days, 14 days, 21 days and 28 days. The serum samples and liver tissues of each group were collected. The pathological changes of liver tissue were observed by HE staining. The activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum were detected by automatic biochemical analyzer. The serum expression levels of miR-122 and miR-155 were detected by real-time quantitative polymerase chain reaction (qPCR). Results The histopathological results showed that liver cells had different degrees of vacuolar degeneration in the experimental groups. A small number of inflammatory cells were observed in the cytoplasm of hepatocytes on the day 3, 5, 7, a large number of hepatocytes were denatured and necrotic on day 21 and regenerated on day 28. It showed a trend of decreasing-increasing on ALT and AST. The expression level of miR-122 was down-regulated in the experimental group after administration, decreased to the lowest level on day 7 (decreased by 81%), and then up-regulated. However, the expression trend of miR-155 was opposite to that of miR-122, reached the peak on day 7, which was 2.88 times that of the control group. MiR-122 was positively correlated with ALT and AST (rs= 0.965 and 0.900, respectively, P＜0.05), while miR-155 was negatively correlated with AST (rs=-0.811, P＜0.05). Conclusion MiR-122 and miR-155 are involved in the occurrence of VPA drug-induced liver injury and are expected to become the early warning indicators.

Key words: valproic acid, chemical and drug induced liver injury, gene expression, microRNAs, miR-122, miR-155