二烯丙基一硫对正己烷中毒大鼠周围神经损伤的干预效果

Study on the effect of diallyl sulfide on peripheral nerve injury in n-hexane intoxicated rats

目的探讨二烯丙基一硫(DAS)对正己烷中毒大鼠周围神经损伤的干预效果。方法成年雄性Wistar大鼠68只,随机选取50只分为5组:空白对照组、DAS对照组(100 mg/kg·bw)、正己烷模型组、DAS低剂量干预组(50 mg/kg·bw)、DAS高剂量干预组(100 mg/kg·bw)。正己烷染毒建立大鼠周围神经损伤模型,使用不同剂量的DAS进行干预,监测大鼠的行为学改变及吡咯加合物变化,并进行血清吡咯加合物的代谢分析,评价干预效果。另选18只大鼠随机分配到正己烷模型组、DAS低剂量干预组、DAS高剂量干预组中,每组各6只,作为卫星组,于第4周进行血清吡咯加合物的代谢动力学研究。结果从第2周开始,与空白对照组比较,正己烷模型组、DAS低剂量干预组、DAS高剂量干预组大鼠体重均降低,差异均有统计学意义(P<0.01)。在第7周实验终点,与正己烷模型组比较,DAS高剂量干预组体重增加(P<0.05),DAS低剂量干预组体重差异无统计学意义(P>0.05)。正己烷模型组、DAS低剂量干预组、DAS高剂量干预组大鼠依次在染毒第2、3、5周开始出现步态异常。在实验终点,与空白对照组比较,正己烷模型组、DAS低剂量干预组、DAS高剂量干预组大鼠步态评分均增高(P<0.01),正己烷模型组、DAS低剂量干预组大鼠转棒潜伏期均缩短(P<0.01)。与DAS对照组比较,DAS高剂量干预组大鼠转棒潜伏期差异无统计学意义(P>0.05)。与正己烷模型组比较,DAS低剂量和DAS高剂量组大鼠转棒潜伏期均增加,差异均有统计学意义(P<0.01)。与空白对照组比较,正己烷模型组、DAS低剂量干预组大鼠的平均神经传导速度均提高,差异均有统计学意义(P<0.01)。与空白对照组比较,DAS对照组和DAS高剂量干预组神经传导速度差异均无统计学意义(P>0.05)。与正己烷模型组比较,DAS低剂量和高剂量干预组大鼠神经传导速度均提高,差异均有统计学意义(P<0.01)。在第7周实验终点,与空白对照组比较,正己烷模型组、DAS低剂量干预组、DAS高剂量干预组大鼠血清、尿、毛发吡咯加合物浓度均升高(P<0.01),DAS对照组大鼠血清、尿、毛发吡咯加合物浓度差异均无统计学意义(P>0.05)。在第7周实验终点,与DAS低剂量干预组比较,DAS高剂量干预组大鼠血清、尿、毛发吡咯加合物浓度均降低,差异均有统计学意义(P<0.05)。大鼠血清吡咯加合物在9~12 h达到峰值,之后开始下降。与正己烷模型组比较,DAS低剂量和高剂量干预组大鼠血清吡咯加合物的半衰期变短、曲线下面积减少,差异均有统计学意义(P<0.05)。结论DAS可能拮抗正己烷引起的大鼠周围神经病变。

Objective To investigate the antagonistic effect of diallyl sulfide(DAS)against peripheral nerve injury induced by n-hexane in rats.Methods A total of 68 adult male Wistar rats were selected,among which 50 were randomly selected and divided into blank control group,DAS control group(100 mg/kg·bw),n-hexane model group,low-dose DAS intervention group(50 mg/kg·bw),and high-dose DAS intervention group(100 mg/kg·bw).A rat model of peripheral nerve injury was established by n-hexane exposure,and the rats were treated with DAS at different doses.The changes in pyrrole adducts and behavior were observed,a metabolic analysis was performed for serum pyrrole adducts,and the intervention effect was evaluated.The remaining 18 rats were randomly assigned to the n-hexane model group,the low-dose DAS intervention group,and the high-dose DAS intervention group,with 6 rats in each group,as satellite groups used for the toxicokinetic analysis of serum pyrrole adducts.Results Compared with the blank control group,the n-hexane model group and low-and high-dose DAS intervention groups had a significant reduction in body weight since week 2(P<0.01).Compared with the n-hexane model group at the end of the experiment at week 7,the high-dose DAS intervention group had a significantly higher body weight(P<0.05),while there was no significant difference in body weight between the n-hexane model group and the low-dose DAS intervention group(P>0.05).The n-hexane model group developed gait abnormality at week 2 of poisoning,while the low-and high-dose DAS intervention groups developed gait abnormality at weeks 3 and 5 of poisoning,respectively.At the end of the experiment,the n-hexane model group and the low-and high-dose DAS intervention groups had a significantly higher gait score than the blank control group(P<0.01).At the end of the experiment,the n-hexane model group and the low-dose DAS intervention group had significantly shorter latency in rotarod test than the blank control group(P<0.01),while there was no significant difference in latency between the DAS control group and the high-dose DAS intervention group(P>0.05).Compared with the n-hexane model group,the low-and high-dose DAS intervention groups had a significant increase in latency in rotarod test(P<0.01).Compared with blank control group,the n-hexane model group and the low-dose DAS intervention group had a significant increase in mean nerve conduction velocity(P<0.01),while there was no significant difference between the blank control group and the DAS control group or high-dose DAS intervention group(P>0.05),and compared with the n-hexane model group,the low-and high-dose DAS intervention groups had a significant increase in nerve conduction velocity(P<0.01).Compared with the blank control group at the end of the experiment at week 7,the n-hexane model group and the low-and high-dose DAS intervention groups had significant increases in the concentration of pyrrole adducts in serum,urine,and hair(P<0.01),while there was no significant difference between the blank control group and the DAS control group(P>0.05),and the high-dose DAS intervention group had a significantly lower concentration of pyrrole adducts in serum,urine,and hair than the low-dose DAS intervention group(P<0.05).Serum pyrrole adducts reached the peak level at 9-12 hours and then started to decrease.Compared with the n-hexane model group,the high-and low-dose DAS intervention groups had a significantly shorter half-life period of serum pyrrole adducts(P<0.01).Compared with the n-hexane model group,the high-and low-dose DAS intervention groups had a significant reduction in the area under the curve of serum pyrrole adducts(P<0.05).Conclusion DAS can antagonize peripheral nerve injury induced by n-hexane.