血液灌流对急性百草枯中毒兔氧化应激和基质金属蛋白酶及其抑制物的影响  

Effects of hemoperfusion on oxidative stress, matrix metalloproteinases and their inhibitors in acute paraquat poisoning rabbits

作　　者：邱俏檬[1] 刘瑶[1] 宋芹[1] 葛赟洪[1] 广亮[1] 卢中秋[1] 梁欢[1] 李萌芳[1] 

机构地区：[1]温州医学院附属第一医院急诊科,325000

出　　处：《中华劳动卫生职业病杂志》2012年第2期89-96,共8页Chinese Journal of Industrial Hygiene and Occupational Diseases

基　　金：浙江省医学创新学科建设计划（11-CX26）;浙江省医学扶植重点学科（07.F04）;温州市科技计划项目（Y20080156）作者单位：通讯作者：卢中秋,E-mail：[e-mail]

摘　　要：目的 观察血液灌流（hemoperfusion,HP）对急性百草枯（PQ）中毒兔氧化指标和基质金属蛋白酶（MMP）-2、MMP-9及基质金属蛋白酶组织抑制因子-1（TIMP-1）的影响,探讨HP对急性PQ中毒兔的治疗作用及机制.方法 将78只日本大耳白兔随机分成正常对照组（N组）6只、PQ中毒组（PQ组）24只、HP治疗组24只、空白对照组（HP对照组）24只.后3组动物分为1、3、7、21d4个观察时间组,N组给予5 ml生理盐水灌胃；PQ组每只兔经口一次灌胃PQ （50 mg/kg）; HP治疗组兔经口一次灌胃PQ （50 mg/kg）后于1h内予活性炭HP治疗2h,HP对照组给予等量生理盐水灌注后1h内予无吸附柱灌流2h.分别测定不同处理后动物肺、肝脏、肾脏中丙二醛（MDA）含量及超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）的活力,并用免疫组化SP法检测MMP-2和MMP-9及TIMP-1表达.结果 随观察时间的延长,PQ组和HP治疗组兔肺、肝、肾组织中MDA含量呈下降趋势,SOD及GSH-Px活力呈上升趋势.PQ组与HP治疗组肺、肝、肾组织MMP-2、MMP-9、TIMP-1在第1天表达均增强,PQ组最为明显,随观察时间的延长,各种阳性表达仍呈较高水平.与N组比较,PQ中毒组和HP治疗组动物肺、肝、肾组织中SOD、GSH-Px活力明显降低,肺、肝、肾组织中MDA含量增高；肺、肝、肾组织中MMP-2、MMP-9、TIMP-1含量明显增加,差异均有统计学意义（P＜0.05,P＜0.01）.与PQ组比较,HP治疗组动物肺、肝、肾组织中SOD、GSH-Px活力明显升高,MDA含量降低；肺、肝、肾组织中MMP-2、MMP-9、TIMP-1含量降低,但高于N组,差异均有统计学意义（P＜0.01）.结论 急性PQ中毒引起的脏器损伤可能与氧化应激及基质金属蛋白酶异常变化有关,HP可能通过改善组织清除自由基的能力及下调兔肺、肝、肾组织中MMP-2、MMP-9和TIMP-1含量,上调组织中MMP-9/TIMP-1比值而发挥救治PQ中毒、保护脏器功能的作用.Objective To observe the effects of hemoperfusion on oxidative stress status and the levels of matrix metallo proteinase （MMP-2,MMP-9）,tissue inhibitor of metalloproteinase （TIMP-1） in lungs,livers and kidneys in paraquat poisoning rabbits,and to explore the mechanism of therapeutic effects induced by HP on acute paraquat poisoning.Methods Seveuty eight rabbits were randomly divided into normal control group （N group,n=6）,exposure groups （PQ group,n=24）,hemoperfusion treatment group （HP treatment group,n=24） and blank control group （HP group,n=24）.The PQ,HPQ and HP groups were divided into 4 observation time groups （ 1,3,7 and 21 d）.N group was exposed to 5 ml normal saline and PQ group was exposed to 50 mg/ kg PQ by oral gavage.In 1 h after PQ exposure,HPQ group was exposed to the activated carbon hemoperfusion for 2 h.The content or activity of MDA,SOD and GSH-Px in lungs,livers and kidneys were detected,the expression levels of MMP-2,MMP-9 and TIMP-1 were measured with immunohistochemical SP method for all groups.Results The contents of MDA in lungs,livers and kidneys of PQ and HPQ groups decreased and the activities of SOD and GSH-Px in lungs,livers and kidneys of PQ and HPQ groups increased with observation time.The expression levels of MMP-2,MMP-9 and TIMP-1 in PQ and HPQ groups enhanced on the first day,PQ group was most obvious.Along with the observation time extended,all kinds of positive expression were still high.Compared with normal control group,the activities of serum SOD and GSH-Px in PQ and HPQ groups declined significantly,but the contents of serum MDA increased; the expression levels of MMP-2,MMP-9 and TIMP-1 in lung,liver and kidney tissues increased obviously,the ration between MMP-9 and TIMP-1 significantly increased （P〈0.05）.Compared with PQ group,the activities of SOD and GSH-Px in HPQ group significantly increased,the content of MDA declined,the expression levels of MMP-2,MMP-9 and TIMP-1 in lung,liver and kidney tissues declined obviously,the ration betwe

关 键 词：灌流 百草枯 基质金属蛋白酶 金属蛋白酶类组织抑制剂 

分 类 号：R595.4[医药卫生—内科学]