正己烷外周神经系统损伤早期效应标志物研究
Study on Early Effect Biomarkers of Peripheral Nervous System Damage Induced by n-Hexane
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摘要:
目的 探讨血清中髓鞘碱性蛋白(MBP)、神经元特异性烯化酶(NSE)、神经生长因子(NGF)、神经丝蛋白(NF)作为正己烷外周神经系统损伤的早期效应标志物的意义。 方法 选取56只清洁级SD大鼠分为0、104、417、1667mg(/kg& #183;d)剂量组,经口亚慢性给予正己烷,染毒18周,通过特异性症状和病理检查验证外周神经损伤情况,同时检测大鼠血清中MBP、NSE、NGF、NF的水平。 结果 正己烷染毒大鼠出现了典型的多发性外周神经病的症状,病理检查证实神经损害。血清中NSE在染毒1周含量即开始明显上升, P<0.05,最大上升幅度为122.94%;血清中NF在染毒2周开始含量明显上升, P<0.05,最大上升幅度为193.35%;大鼠血清中MBP水平、血清NGF水平仅在个别时间点有改变。步态评分与血清NSE、NF、NGF、MBP的Pearson相关系数分别为0.608(P<0.05)、0.595(P<0.05)、-0.284(P>0.05)、0.179(P>0.05);以NSE和NF计算出来的正己烷毒效应基准剂量(bench mark dose, BMD)、基准剂量可信区间下限(bench mark dose lower confidence limit, BMDL)分别约为150、105 mg(/kg& #183;d)。 结论 正己烷致大鼠神经系统损伤的敏感性指标以血清NSE、NF灵敏度最高,浓度上升早于动物步态症状的出现,改变幅度大,可作为较好的正己烷毒效应标志物;血清NGF、血清MBP作为正己烷毒效应标志物的意义仍需进一步探讨。 Abstract:Objective To determine the valuable significance of myelin basic protein (MBP), neuron-specific enolase (NSE), nerve growth factor(NGF), and neurofilament(NF) in serum as early effect biomarkers of peripheral nervous system damage induced by n-hexane. Methods n-Hexane was administered by gavage to rats sub-chronically. Peripheral nerve damage was verified by specific symptoms and pathological examination. Simultaneously MBP, NSE, NGF, and NF levels in serum of rats were detected. Results Typical symptoms of multiple peripheral neuropathy appeared in rats exposed to n-hexane, nerve damage was confirmed by pathological examination. Serum NSE and NF levels significantly increased starting from 1st or 2nd week after intoxicated in different dose groups, respectively (P < 0.05), the maximum raise were 122.94% and 193.35% respectively. Serum NGF and MBP levels changed only in very few time points. Pearson correlation coefficient between gait score and serum NSE, NF, NGF, MBP were 0.608 (P < 0.05), 0.595 (P < 0.05), -0.284 (P > 0.05), and 0.179 (P > 0.05)respectively. Bench mark dose (BMD) and bench mark dose lower confidence limit (BMDL)calculated according to NSE and NF were about 150 mg (/kg& #183; d) and 105 mg (/kg& #183; d). Conclusion Serum NSE, NF were the most sensitive indicators of peripheral nervous system damage, whose increase preceded the symptom manifested in the animals intoxicated and changed substantially, so they could be used as good biomarkers of toxic effect induced by n-hexane. NGF had poor sensitivity in this study. Significance of MBP remained to be verified if used as a biomarker of toxic effect induced by n-hexane.
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