维生素 C 治疗百草枯中毒大鼠的量效关系

目的：探讨维生素C治疗百草枯(paraquat，PQ)中毒大鼠的疗效及量效关系。方法：将40只Sprague-Dawley(SD)大鼠随机分为对照组、中毒组和维生素C1组、C2组，每组10只。通过胃内一次性灌注150 mg/kg PQ，建立PQ中毒SD大鼠模型。中毒组给予30 mg/kg甲基强的松龙、2.5 mg/kg环磷酰胺腹腔注射；维生素C1组、C2组在中毒组基础上给予两种浓度的维生素C(5，500 mg/kg)，以生理盐水稀释成5 mL/kg，股静脉注射；对照组仅以生理盐水进行相应处理。于实验后36 h检测大鼠血浆中丙二醛、肝肾功能，并行动脉血气分析，采血后处死大鼠取肺组织行病理切片、湿干重比等检查；取肝组织行比色法检测谷胱甘肽过氧化物酶(glutathione peroxidase，GSH-PX)，Western印迹检测Bcl-2表达等。结果：维生素C1组中丙二醛低于中毒组，GSH-PX高于中毒组，肝肾功能较中毒组有明显改善(均P<0.01)；维生素C2组丙二醛高于中毒组，其肝肾功能较中毒组也呈恶化趋势(均P<0.01)。中毒组中Bcl-2较对照组表达减低，维生素C1组中Bcl-2较中毒组表达增强，而维生素C2组中Bcl-2较中毒组表达减弱(均P<0.01)。但维生素C1组、C2组在肺功能、湿干重比、病理学等与中毒组差异无统计学意义(均P>0.05)。结论：低剂量维生素C可能通过抗氧化、抑制PQ导致的细胞凋亡等途径对PQ中毒大鼠的肝肾功能有部分的保护作用，而高剂量维生素C反而有促氧化作用；同时，维生素C未呈现出对PQ中毒时肺的保护作用。

Dose-effect relationship between vitamin C andparaquat poisoning rats

Objective: To explore the dose-effect relationship between vitamin C and paraquat (PQ) poisoning rats.Methods: A total of 40 Sprague-Dawley (SD) rats were randomly divided into 4 groups: a controlgroup, a PQ poisoning group, a vitamin C group 1 and a vitamin C group 2 (n=10 in each group).150 mg/kg PQ was perfused into rat stomach to establish PQ poisoning rat model. In PQ poisoning group, 30 mg/kg methylprednisolone and 2.5 mg/kg cyclophosphamide were injected peritoneallyon the basis of PQ poisoning rat model. In vitamin C1 and C2 group, vitamin C was injected ata dosage of 5 or 500 mg/kg, respectively. The control group only received normal saline (NS).The malondialdehyde (MDA), liver and kidney function as well as arterial blood gas in the bloodwere examined 36 h later. At the end, the rats were killed and took the liver tissues for pathologicalexamination and weight ratio calculation. The glutathione peroxidase (GSH-PX), ctychrome C (CytC) in the liver tissues were detected by chromatometry, and the Bcl-2 was detected by Western blot.Results: Compared with the PQ poisoning group, the MDA and Cyt C were decreased, theGSH-PX was increased, and liver and kidney functions were improved in the vitamin C group 1(all P<0.01); but in the vitamin C group 2, the MDA increased and liver/kidney functions wereimpaired (all P<0.01). The expression of Bcl-2 in the PQ poisoning group was lower than that in thecontrol group; compared with the PQ poisoning group, it was increased in the vitamin C1 group,while it was decreased in the vitamin C group 2 (both P<0.01). There was no obvious difference inthe lung function, wet/dry weight ratio and pathological changes between the poisoning group andexperimental groups (all P>0.05).Conclusion: Vitamin C at the low dose shows a certain degree of protection for the liver andkidney in the PQ poisoning rats model through it antioxidative activity and anit-apoptosis activity,while vitamin C at the high does may promote oxidation. Meanwhile, vitamin C doesn’t showprotective effect on lung in the PQ poisoning rats.