CYP2E1在大蒜油拮抗正己烷神经损伤中的作用

目的 研究CYP2E1在大蒜油(garlic oil,GO)阻止正己烷(n-hexane)致大鼠周围神经损伤的作用及其机制.方法 雄性Wistar大鼠50只,随机分为正常对照组、GO对照组、正己烷模型组、GO低剂量加正己烷组和高剂量加正己烷组(n=10).模型组及GO低、高剂量组大鼠分别给予2000 mg/kg正己烷灌胃;GO低、高剂量组大鼠在正己烷灌胃前1h分别给予40、80 mg/kg GO灌胃,GO对照组给予80 mg/kg,每周6次,持续10周.每2周测步态评分,监测大鼠周围神经损伤情况.于第10周末,断头处死大鼠,检测肝组织中CYP2E1表达及活力的改变,以及血清中2,5-己二酮(2,5-HD)含量的变化.结果 与正常对照组相比,GO对照组大鼠肝脏中CYP2E1含量及活力分别下降83.1％和48.3％,且差异均有统计学意义(P＜0.01);与正常对照组相比,模型组大鼠肝脏中CYP2E1含量及活力分别升高122.5％和72.2％,且差异均有统计学意义(P＜0.01);与模型组相比,GO低、高剂量组大鼠肝脏中CYP2E1含量分别降低32.9％和39.1％,且CYP2E1活力分别降低27.4％和44.5％,差异均有统计学意义(P＜0.01);与模型组相比,GO低、高剂量组大鼠血清中2,5-HD含量分别下降47.7％和78.7％,且差异均有统计学意义(P＜0.01).各组步态评分显示,模型组及GO低、高剂量组均明显高于对照组,但GO低、高剂量组低于模型组,差异有统计学意义(P＜0.05).结论 GO能够有效拮抗正己烷的外周神经损伤,其机制可能与肝脏中CYP2E1含量及活力降低,使正己烷代谢为2,5-HD减少有关.

The role of CYP2E1 in the protection of garlic oil's from n-hexane-induced neurotoxicity

Objective To study the role of CYP2E 1 in the protective effects and mechanism of garlic oil (GO) on the peripheral nerve injuries induced by n-hexane.Methods Fifty male Wistar rats were randomly divided into five groups (n=10):the control,the GO (80 mg/kg) control,the n-hexane (2000 mg/kg) model,the low dose GO (40 mg/kg) plus n-hexane,and the high dose GO (80 mg/kg) plus n-hexane groups.All rats were treated by intragastric administration 6 times a week for 10 weeks.The gait scores were determined every two weeks for monitoring the peripheral neurotrosis.All rats were sacrificed in 10 weeks,the activities and expression levels of hepatic CYP2E 1 and 2,5-HD in serum were examined.Results As compared with control group,the content and activity of hepatic CYP2E1 in GO control group reduced by 83.1％ and 48.3％ respectively (P＜0.01),the content and activity of hepatic CYP2E1 in model group increased by 112.5％ and 72.2 ％respectively (P＜0.01).As compared with model group,the contents of hepatic CYP2E1 in low dose and high dose GO groups reduced by 32.9％ and 39.1％ respectively,the activities of hepatic CYP2EI in low dose and high dose GO groups reduced by 27.4％ and 44.5％ respectively (P＜0.01); the contents of serum 2,5-HD in low dose and high dose GO groups reduced by 47.7％ and 78.7％ respectively (P＜0.01).The gait scores in model,low dose and high dose GO groups were significantly lower than that in control group,but the gait scores in low dose and high dose GO groups were significantly lower than that in model group (P＜0.05).Conclusion Garlic oil can effectively reduce the peripheral neurotrosis induced by n-hexane due to the decreased content and activity of hepatic CYP2E 1,resulting in the reduced formation of 2,5-HD from n-hexane.