Effects of subchronic 2,5-hexanedione exposure on expressions of myelin protein zero and neurofilament protein in rat sciatic nerve tissue
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摘要: 目的观察2,5-己二酮(2,5-HD)暴露对大鼠坐骨神经组织超微结构及P0(myelin protein zero)和神经丝(neurofilament, NF)表达影响, 探讨它们之间的关联性。方法成年雄性SD大鼠40只, 随机分成对照组(生理盐水)和低、中、高剂量染毒组(100、200、400 mg/kg腹腔注射2,5-HD), 每组10只, 每周连续5 d, 1次/d。染毒5周后处死动物, 取坐骨神经, 电镜观察形态学改变, RT-PCR 和 Western blot 检测 P0、NF-L、NF-M 和 NF-H 基因和蛋白表达水平。结果随染毒剂量升高, 大鼠坐骨神经髓鞘形状渐不规则, 并出现内折现象;轴索形状渐不规则, 部分发生萎缩;神经丝数量渐少, 排列稀疏。与对照组比较, 400 mg/kg 2,5-HD 组大鼠坐骨神经 P0 mRNA 表达量(0.75±0.03)、NF-L、NF-M 和 NF-H mRNA 表达量[分别为(0.35±0.07)、(0.25±0.04)、(0.37±0.05)]明显下降(P<0.05);与对照组比较, 400 mg/kg 2,5-HD 组大鼠坐骨神经 P0 蛋白表达量(0.79±0.04)、NF-L、NF-M 和 NF-H 蛋白表达量[分别为(0.26±0.02)、(0.12±0.03)、(0.22±0.02)]明显降低(P<0.05)。结论亚慢性 2,5-HD 暴露导致的外周神经病变可能与 P0 和 NF 表达异常有关, 这些蛋白可能是 2,5-HD 攻击外周神经系统的靶点。
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关键词:
- 2,5-己二酮(2,5-HD) /
- 坐骨神经 /
- 超微结构 /
- 髓鞘蛋白P0 /
- 神经丝(NF)
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.-
Key words:
- 2,5-hexanedione /
- sciatic nerve /
- ultrastructure /
- myelin protein zero /
- neurofilament
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