Abstract: ObjectiveTo explore the role of hedgehog(Hh) signaling pathway in excessive fluorine-induced liver injury in rats.MethodsThirty-six healthy Sprague-Dawley(SD) rats were randomly divided into three groups(6 males and 6 females in each group):a control group and two low- and high-dose fluorine groups exposed to 5,50 mg/L fluorine in drinking water.After 6 months,urine and bone fluorine contents were detected using fluorine ion electrode method.Indicators of liver function were determined with automatic blood chemical analyzer.The protein and mRNA expressions of Indian hedgehog(Ihh),smoothened protein(Smo),and glioma-associated oncogene homolog 1(Gli1) were detected with immunocytochemistry,Western blot,and real-time-PCR.The activity of total superoxide dismutase(T-SOD), glutathione peroxidase(GSH-PX), glutamine synthetase(GS), and the content of lipid peroxide(LPO) were determined with oxidative stress kit.ResultsCompared with the control group,urine and bone fluoride contents of the fluorine exposure groups increased;the rats in high-dose fluorine exposure group showed significantly increased activity of serum alanine transaminase(73.42±6.98 U/L),aspartate transaminase(161.08±8.59 U/L),increased protein and mRNA expressions of Ihh(71.41±4.18 and 1.20±0.17),Smo(83.83±5.26 and 3.13±0.19),Gli1(81.14±25.44 and 5.35±0.52),and increased content of LPO(10.29±1.81 μmol/gprot) and significantly decreased activity of SOD(5.08±0.64 U/mgprot),GSH-PX(5.53±0.83 U/mgprot),and GS(19.22±1.84 U/mgprot)(all P<0.05).ConclusionHh signaling pathway and oxidative stress may be involved in the pathogenesis of fluorosis liver injury.