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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P0mRNA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。
Objective To investigate the effect of 2,5-hexanedione (2,5-HD) exposure on the ultrastructure of the sciatic nerve and the expression of myelin protein zero and neurofilament (NF) in rats and to explore the relationship between them . Methods Forty adult male Sprague-Dawley rats were randomly divided into control group (saline) and low, medium and high dose exposure groups (100, 200, 400 mg / kg intraperitoneal injection of 2,5-HD) Continuous for 5 days a week, 1 time / d. The rats were sacrificed 5 weeks after the operation. The sciatic nerve was taken and the morphological changes were observed by electron microscope. The gene and protein expressions of P0, NF-|ÊL, NF-|ÊB and NF-|ÊB were detected by RT-PCR and Western blot. Results With the increase of exposure dose, the shape of myelin sheath of sciatic nerve in rats gradually became irregular and showed an internal fold. The shapes of axons gradually became irregular and some of them shrank. The number of neurofilaments gradually decreased and arranged sparsely. Compared with the control group, the expression of P0 mRNA in the sciatic nerve of the 400 mg / kg 2,5-HD group was (0.75 ± 0.03), the expression of NF-κB, NF-κB and NF-κB mRNA were [0.35 ± 0.07 (P0.05 ± 0.05). Compared with control group, the expression of P0 protein in sciatic nerve of 400 mg / kg 2,5-HD group (0.79 ± 0.04) and NF- L, NF-κB and NF-κB were significantly decreased (P <0.05), respectively (0.26 ± 0.02, 0.12 ± 0.03, 0.22 ± 0.02) Conclusion Peripheral neuropathy caused by sub-chronic 2,5-HD exposure may be related to the abnormal expression of P0 and NF. These proteins may be targets of 2,5-HD attack on the peripheral nervous system.