二巯丙磺钠对百草枯急性中毒大鼠肺组织基质金属蛋白酶-9 mRNA及其金属蛋白酶组织抑制剂-1 mRNA表达的影响  

Effect of sodium captopropane sulfonic on expressions of matrix metalloproteinase-9 mRNA and tissue-inhibitor of metalloproteinase-1 mRNA in lungs of paraquat poisoning rats

作　　者：韩国强[1,2] 邱俏檬[3] 卢中秋[3] 贺晓燕[3] 洪广亮[3] 何飞[3] 梁欢[3] 

机构地区：[1]温州医学院附属第二医院 [2]温州医学院附属育英儿童医院PICU [3]温州医学院附属第一医院急诊科,浙江温州325000

出　　处：《中国药理学与毒理学杂志》2010年第1期25-29,共5页Chinese Journal of Pharmacology and Toxicology

基　　金：浙江省医学扶植重点建设学科计划资助项目(07-F04);浙江省高校科研计划重点项目资助(Z200803373);浙江省自然科学基金资助项目(Y-2080977)~~

摘　　要：目的探讨二巯丙磺钠(DMPS)救治百草枯(PQ)急性中毒大鼠作用机制。方法120只雄性SD大鼠随机分为正常对照组,DMPS(200mg.kg-1,ip)对照组,PQ急性中毒(20mg.kg-1,ip)1,3,7,14和28d组以及DMPS干预(先给DMPS,15min后再给PQ)1,3,7,14和28d组。应用RT-PCR技术检测PQ急性中毒组大鼠及DMPS干预组大鼠肺组织中基质金属蛋白酶9(MMP-9)mRNA和金属蛋白酶1组织抑制剂(TIMP-1)mRNA的表达。结果PQ急性中毒组早期肺组织毛细血管扩张充血,炎症细胞浸润,后期出现较大范围慢性炎症病灶,纤维组织增生。与正常对照组比,MMP-9mRNA明显升高,分别为1.13±0.06,1.32±0.04和1.10±0.06,0.85±0.06和0.75±0.05,TIMP-1mRNA明显升高,分别为1.14±0.08,1.29±0.05,1.61±0.09,1.83±0.13和1.73±0.08;7,14和28d MMP-9mRNA/TIMP-1mRNA比值明显低于正常对照,分别为0.68±0.03,0.46±0.04和0.43±0.06;DMPS干预后,MMP-9mRNA1,3和7d和TIMP-1mRNA1,3,7,14和24d表达低于PQ中毒组,MMP-9mRNA分别为1.05±0.03,1.17±0.05和0.93±0.09;TIMP-1mRNA分别为10.0±0.07,1.15±0.09,1.09±0.06,1.16±0.08和1.23±0.09;MMP-9mRNA/TIMP-1mRNA比值略低于DMPS对照组,但高于PQ中毒组,分别为0.85±0.05,0.63±0.04和0.58±0.02(均P<0.05)。结论DMPS可能通过下调大鼠肺组织MMP-9mRNA和TIMP-1mRNA表达,上调肺组织MMP-9mRNA/TIMP-1mRNA比值发挥救治PQ中毒作用。OBJECTIVE To study the changes in matrix metalloproteinase-9（MMP-9） mRNA,tissue-inhibitor of metalloproteinase-1（TIMP-1） mRNA and the ratio of MMP-9 mRNA/TIMP-1 mRNA in the lungs of paraquate poisoning rats,and to investigate the protective effects of sodium dimercaptopropane sulfonate（DMPS,Unithiol）.METHODS One hundred and twenty male SD rats were divided into 12 groups（n=10） randomly：normal control,DMPS control,PQ poisoning 1,3,7,14 and 28 d model groups,（DMPS＋PQ） 1,3,7,14 and 28 d groups.PQ poisoning model was established by intraperitoneal injecting paraquate.The expression of MMP-9 mRNA and TIMP-1 mRNA in lung tissues was detected by RT-PCR.RESULTS ①By observing the changes of action and observing the lung tissues sections,the rats＇ PQ poisoning models was successfully established.②The histopathology of lung showed infiltration of inflammatory cell in acute phase（within 2 weeks）,the inflammation decreased gradually after 2 weeks,hyperplasia of collagen and pulmonary fibrosis were instead.Howerer,the pathological changes were alleviated obviously in the（DMPS＋PQ） groups.③Compared with the PQ groups,the expression of MMP-9 mRNA and TIMP-1 mRNA in lungs diminished greatly in the DMPS＋PQ groups after rats injected DMPS（P〈0.05）;the ratio of MMP-9/TIMP-1 mRNA was bigger at 7,14 and 28 d in the DMPS＋PQ groups after rats injected DMPS.CONCLUSION Down-regulation of the expression of MMP-9 mRNA and TIMP-1 mRNA and up-regulation ratio of MMP-9 mRNA/TIMP-1 mRNA by DMPS may be one of mechanisms by which pulmonary injury and pulmonary fibrosis are prevented in the acute paraquate poisoning.

关 键 词：二巯丙磺钠 百草枯 基质金属蛋白酶9 金属蛋白酶1组织抑制剂 基因表达 

分 类 号：R595.4[医药卫生—内科学]