Expression of Janus kinase/signal transduction and transcriptional activation (JAK1 and STAT3) in liver of fluorosis rats / 中华地方病学杂志

ABSTRACT

Objective To explore the role of Janus kinase/signal transduction and transcriptional activation (JAK/STAT) pathway in rat liver damaged by excessive fluorine.Methods Thirty-six healthy Sprague-Dawley (SD) rats were randomized by weight and divided into three groups (6 males and 6 females per group)a control group (drunk water containing NaF ＜1 mg/L) and two fluorosis groups (drunk water containing NaF of 5 mg/L and 50 mg/ L).After 6 months of experiment treatment,the fluorine contents of urine and bone were detected by fluorine-ion electrode method.The rats liver function was determined by automatic blood chemical analyzer.The protein expression of Janus kinase (JAK1),signal transducer and activator of transcription (STAT3),B-cell lymphoma/ leukemia-2 (Bcl-2) and Bcl-associated x protein (Bax) were detected by immunohistochemistry (IHC) and protein imprinting (Western blotting).The activity of superoxide dismutase (SOD),glutathione peroxidase (GSH-PX) and the content of lipid peroxide (LPO) in liver tissue were determined with oxidative stress kit.Results The fluorine contents in the urine and bone in low-[(1.90 ± 0.12)mg/L,(210.37 ± 15.81)mg/kg] and high-dose [(2.20 ± 0.17)mg/L,(222.84 ± 10.21)mg/kg] fluoride groups were higher than those of control group [(1.74 ± 0.11)mg/L;(165.48 ± 10.37) mg/kg,F =33.840,69.149,P ＜0.05];the activity of serum alanine aminotransferase (ALT) and aspartate transaminase (AST) in high-dose fluorosis group [(69.83 ± 11.18),(167.56 ± 50.85) U/L] was higher than those of control group [(42.67 ± 7.07),(126.31 ± 16.76)U/L,F =32.135,4.984,all P ＜0.05];the protein expression of JAK1,STAT3 and Bax (1.56 ± 0.31,1.49 ± 0.49,1.41 ± 0.55) in high-dose fluorosis group were significantly higher than those of control group(1.01 ± 0.11,1.04 ± 0.15,0.87 ± 0.21,F=10.923,5.361,5.009,all P＜0.05),and Bcl-2 (0.61 ± 0.15) was significantly lower in high-dose fluorosis group than control group (1.04 ± 0.17,F =16.017,P ＜0.05);the activities of SOD and GSH-PX [(7.22 ± 0.88),(7.23 ± 2.47)U/mg prot] were significantly lower in high-dose fluorosis group than control group [(9.52 ± 1.51),(12.01 ± 5.16)U/mg prot,F =11.627,4.824,all P ＜0.05],and the contents of LPO [(9.23 ± 2.24)μmol/g prot] was significantly higher in high-dose fluorosis group than control group [(6.09 ± 1.55)μmol/g prot,F =7.457,P ＜0.05].Conclusion JAK/STAT signaling pathway and the oxidative stress,apoptosis may be the pathogenesis of liver damage in chronic fluorosis.