百草枯中毒大鼠的肝损伤及抗氧化药物对其保护作用  

The paraquat-induced liver injury in rats and the protective effect of antioxidative drugs on it

作　　者：高艳敏[1] 赵雄[1] 丁佳[1] 刘俊平[1] 田艳[1] 倪鎏达[2] 范竹萍[1] 

机构地区：[1]上海交通大学医学院附属仁济医院健康保健中心,上海市消化疾病研究所,200025 [2]上海解放军第八五医院南京军区肝病临床研究中心

出　　处：《肝脏》2009年第3期210-213,共4页Chinese Hepatology

基　　金：上海市重点学科建设项目(Y0205);全军医药卫生科研基金

摘　　要：目的研究百草枯(PQ)对肝脏的损伤作用及其机制,并用抗氧化药物N-乙酰半胱氨酸(NAC)和谷胱甘肽(GSH)干预,观察药物对PQ中毒大鼠的肝脏保护作用并探讨药物作用机制。方法33只清洁级SD大鼠随机分为4组:PQ单纯染毒组、NAC防治组、GSH防治组和正常对照组。单纯染毒组一次性灌胃给予PQ100mg/kg染毒;防治组分别于染毒前半小时、染毒后半小时及持续7d内同一时间分别腹腔注射NAC150mg/kg、GSH100mg/kg。各组在染毒后第1、3、7天采血取样,检测血浆及肝组织匀浆中的ALT、AST水平及SOD活力、GSH-Px活力和MDA含量。结果PQ染毒后第1天各组大鼠血浆及肝组织匀浆中的ALT、AST水平及MDA含量较正常对照组明显升高(P<0.05),而防治组明显低于单纯染毒组(P<0.05);各组大鼠血浆及肝匀浆SOD及GSH-Px活力均较正常对照组下降(P<0.05),但防治组明显高于单纯染毒组(P<0.05)。实验结束时防治组血浆及肝匀浆中ALT、AST水平和MDA含量明显低于单纯染毒组(P<0.05),SOD活力、GSH-Px活力防治组明显高于单纯染毒组(P<0.05),部分指标NAC组优于GSH组(P<0.05)。结论氧应激在PQ致大鼠肝损伤中发挥重要作用,NAC和GSH对改善PQ中毒患者肝细胞抗氧化能力有积极作用。Objective To study the mechanism of paraquat leading to liver injury and the protective effect of glutathione （GSH） and N-acetyl-L cysteine （NAC） on it. Methods Thirty-three SD rats were randomly divided into 4 groups： paraquat exposure group, GSH treatment group, NAC treatment group and normal control group. Gastric perfused with paraquat 100 mg/kg once, two treatment groups were exposed to GSH 100 mg/kg, NAC 150 mg/kg by intraperitoneal injection in half an hour before and after gastric perfusion and continuing 7 days. To detect the levels of ALT, AST, the vitality of SOD and GSH-PX, MDA content, rats were sacrificed to obtain blood and liver samples in the day 1,3,7. Results The levels of plasma and liver homogenate ALT, AST increased obviously compared with control group at first day（P〈0.05）. But the levels of liver enzymes and MDA decreased in NAC and GSH treatment groups compared with PQ group （P 〈0.05）. The SOD and GSH-PX vitality decreased in all groups compared with normal control group（P〈0. （15）. But both improved in NAC and GSH group compared with PQ group. In the end of experiment, the levels of liver enzymes and MDA decreased in NAC and GSH treatment groups compared with PQ group（P〈0.05）, and the SOD and GSH-PX vitality increased strikingly compared with PQ group（P〈0.05）. NAC was superior to GSH for improving some indicators. Conclusion Oxidative stress played a important role in PQ induced liver injury and NAC and GSH can improve the hepatic antioxidant ability.

关 键 词：急性肝损伤 百草枯 还原型谷胱甘肽 N乙酰半胱氨酸 氧化还原系统 

分 类 号：R595.4[医药卫生—内科学]