[Rutin activates AMPKα to ameliorate liver damage caused by perfluorooctanoic acid in mice].

OBJECTIVE: To study the protective effect and mechanism of rutin on perfluorooctanoic acid(PFOA)-induced liver damage in mice.

METHODS: A total of 24 male ICR mice were randomly divided into 3 groups, 8 in each group: control group(ctrl group: ddH_2O), perfluorooctanoic acid group(PFOA group: PFOA 20 mg/(kg·d)), rutin intervention group(rutin+PFOA group: PFOA 20 mg/(kg·d)+rutin 20 mg/(kg·d)), normal diet, oral gavage, daily observation, weighting, and recording. After 14 days of treatment, the liver was quickly stripped and weighted after blood sampling and execution. Part of the liver tissue is fixed in 4% paraformaldehyde for HE staining and PAS staining; glutamic-pyruvic transaminase(GPT) activity in the sera samples and triglyceride(TG), total cholesterol(TC), malondialhyde(MDA) content in hepatic tissue homogenate, as well as the activity of some enzymes were assayed; Using western blot to detect adenylate activated protein kinase α(AMPKα) and phosphorylated adenylate-activated protein kinase α(p-AMPKα) expression levels.

RESULTS: PFOA caused a significant decrease in the weight of mice, a significant increase in liver weight and liver relative body weight coefficient(P& lt; 0.05), hepatocyte cord dissociation, hepatocyte swelling, dissolution, and obvious damage, and PAS staining positive result were significantly reduced. The GPT activity of the PFOA group was 204.63±11.26 U/L, which was significantly higher than that of the control group(28.80±4.51 U/L)(P& lt; 0.05); The contents of TG, TC and MDA in the liver tissues of mice were 4.89±0.51 mmol/g prot, 8.06±0.84 mmol/g prot and 315.38±60.79 nmol/mg prot, respectively, which were significantly higher than those of the control group(P& lt; 0.05); The activity of T-SOD was 4175.56±334.96 U/mg prot, which was significantly lower than that of the control group(P& lt; 0.05); After rutin intervention, compared with PFOA exposure group, the weight of the mice did not change significantly(P& gt; 0.05), however, the liver weight and the relative weight coefficient of the liver were significantly reduced(P& lt; 0.05), and the hepatocytes swollen and cell lysis were attenuated, the structure of cell cord changed clear, the positive PAS staining cells were significantly increased, the GPT activity of the rutin intervention group was 168.75±18.32 U/L, which was significantly lower than that of the PFOA group(P& lt; 0.05); The contents of TC and MDA in the liver tissues of mice were 4.25±0.77 mmol/g prot and 211.27±44.44 nmol/mg prot, respectively, which were significantly lower than those in the PFOA group(P& lt; 0.05); The T-SOD activity was 7368.88±673.09 U/mg prot, which was significantly higher than that of the PFOA group(P& lt; 0.05). There was no significant difference in AMPKα protein expression in the liver tissues of the three groups. Compared with the PFOA group, the p-AMPKα protein expression in the PFOA+rutin group was significantly up-regulated.

CONCLUSION: PFOA exposure can cause liver damage and lipid accumulation in mice. Rutin has a certain protective effect on this damage, which may be related to rutin& apos; s activation of AMPKα protein expression to effectively correct TG levels and enhance the activity of antioxidant enzymes.