Abstract: ObjectiveTo explore the changes in ultrastructure and the expressions of myelin protein zero(P₀) and neurofilament protein(NF) in sciatic nerve tissue of rats subchronically exposed to 2,5-hexanedione(2,5-HD) and the relationship between the changes.MethodsForty adult male Sprague-Dawley rats were randomly divided into four groups(10 in each group) and treated with 2,5-HD saline solution at dose of 0,100,200,and 400 mg/kg by intraperitoneal injection for 5 days a week.After 5 weeks'treatment,the rats were executed and the sciatic nerve tissues were divided.Morphological changes in the tissues were observed with electron microscopy.Expressions of P₀,NF-L,NF-M and NF-H(for low,middle,and high molecular weight neurofilament protein) were analyzed with real-time reverse transcription PCR(RT-PCR) and Western blot.ResultsWith the increased exposure,the myelin sheath became irregular in shape and some of them enfolded; the axon also became irregular in shape and some of them appeared atrophy; while,the neurofilament decreased in number and arranged scattered.In 400 mg/kg 2,5-HD exposed group,the P₀ mRNA expression was 0.75±0.03 and the NF-L,NF-M,and NF-H mRNA expressions decreased by 0.35±0.07,0.25±0.04,and 0.37±0.05,respectively,when compared with those of the control group(P<0.05 for all).The protein expressions of P₀ was 0.79±0.04,and the NF-L,NF-M,and NF-H protein expressions decreased by 0.26±0.02,0.12±0.03,and 0.22±0.02,respectively(P<0.05 for all).ConclusionP₀ and NFs may be involved in the peripheral nervous damage induced by 2,5-HD exposure and they may be the target molecules of the toxincant.