2,5-己二酮对大鼠神经组织中低分子量神经丝降解的影响

摘要

Objective To investigate the effect of 2,5-hexanedione (HD) on degradation of lowmolecular-weight neurofilaments (NF-L) in nervous tissue of rats,and to explore the molecular mechanism of nhexane neuropathy.Methods Fifty male Wistar rats were randomly divided into one-week poisoning group (n=10),two-week poisoning group (n=10),three-week poisoning group (n=10),four-week poisoning group (n=10),and control group (n=10).In the four poisoning groups,a rat model of n-hexane neuropathy was established by intraperitoneal injection of HD (400 mg/kg/d).The change in the sciatic nerve ultrastructure of each rat was observed under an electron microscope.The progression of HD-induced peripheral neuropathy was evaluated using a gait scooring system.The degradation rates of NF-L in the sciatic nerve and spinal cord of each rat were measured by Western Blotting.Results The rats showed decrease in muscle strength and abnormal gait after two weeks of HD poisoning and mild or moderate paralysis after four weeks of HD poisoning.The sciatic nerve showed degenerative change,according to electron microscope observation.Compared with the control group,the two-week poisoning group,three-week poisoning group,and four-week poisoning group had the NF-L degradation rates decreased by 25.8%,70.4%,and 69.7%,respectively,in the supernatant fraction of sciatic nerve,and by 14.7%,64.6%,and 67.3%,respectively,in the sediment fraction of sciatic nerve,all showing a significant difference (P＜0.01).Compared with the control group,the one-week poisoning group had the NF-L degradation rate decreased by 33.87% in the supernatant fraction of spinal cord,the four-week poisoning group had the NF-L degradation rate increased by 16.2% in the supernatant fraction of spinal cord,and the one-week poisoning group and two-week poisoning group had the NF-L degradation rates decreased by 46.3% and 13.0% in the sediment fraction of spinal cord,all showing a significant difference (P＜0.01).Conclusion HD poisoning significantly inhibits NF-L degradation in the sciatic nerve,which may be associated with NF degeneration and accumulation in the axons of patients with n-hexane neuropathy.%目的 研究2,5-己二酮(HD)对大鼠神经组织中低分子量神经丝(NF-L)降解的影响,探讨正己烷中毒性神经病发生的可能机制.方法 雄性Wistar大鼠50只随机分为1、2、3、4周染毒组和对照组,每组10只.经腹腔注射HD(400 mg/kg)染毒动物,剂量为,建立正己烷中毒性神经病模型.电子显微镜观察大鼠坐骨神经的超微结构变化,步态评分评价大鼠周围神经病症状的进展,免疫印迹法(Westem blot)检测坐骨神经和脊髓组织中NF-L降解率的变化.结果 HD染毒2周后,大鼠逐渐出现肌力降低、步态异常等表现,至染毒4周结束时大鼠呈现轻中度瘫痪,电子显微镜观察显示坐骨神经出现退行性病变.与对照组相比较,2、3、4周染毒组大鼠坐骨神经上清和沉淀组分中NF-L降解率均呈进行性下降,其中上清NF-L降解率分别下降25.8％、70.4％和69.7％,沉淀中NF-L降解率分别下降14.7％、64.6％和67.3％,差异均有统计学意义(P＜0.01).在脊髓组织中,与对照组相比较,1周染毒组脊髓上清中NF-I,降解率下降33.87％,4周染毒组脊髓上清中NF-L降解率升高16.2％,1、2周染毒组脊髓沉淀中NF-L降解率分别下降46.3％和13.0％,差异均有统计学意义(P＜0.01).结论 HD染毒显著抑制了坐骨神经中NF-L的降解,这可能与正己烷中毒性神经病轴突中NF变性堆积有关.