创伤弧菌脓毒症大鼠肝脏MMP-2、MMP-9及TIMP-2基因表达及抗菌药物干预对其的影响  

Expression of matrix metalloprotease2/9 and tissue inhibitor of metallo-proteinase-2 in the liver tissue of rats with vibrio vulnificus sepsis and the effects of antibacterial agents on these genes

作　　者：李景荣[1] 熊术道[2] 梁欢[1] 卢中秋[1] 

机构地区：[1]温州医学院附属第一医院急诊科 [2]复旦大学上海医学院免疫学系,上海200032

出　　处：《中国临床药理学与治疗学》2009年第4期410-415,共6页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：浙江省科技厅科研基金资助项目(2005C30009);浙江省医药卫生科学研究基金计划(2007B145);温州市科技局课题(Y20060243)

摘　　要：目的:观察创伤弧菌脓毒症SD大鼠肝脏间质金属蛋白酶-2(MMP-2)、MMP-9以及金属蛋白酶组织抑制剂(TIMP-2)基因表达的变化规律以及联用头孢哌酮钠和左氧氟沙星对其基因表达的影响。方法:清洁级SD雄性大鼠110只,随机分为正常对照组(CN组,n=10)、创伤弧菌脓毒症模型组(VV组,n=50)及脓毒症模型+药物干预组(AA组,n=50)。观察大鼠行为学改变,RT-PCR检测各组MMP-2、MMP-9以及TIMP-2基因mRNA水平表达的变化。结果:创伤弧菌感染后早期MMP-2及MMP-9基因mRNA水平表达明显上调,TIMP-2表达呈下降(与对照组比较,P<0.05);抗生素干预后,MMP-2及MMP-9基因表达可见下调(与VV组比较,P<0.05),TIMP-2表达上调(与VV组比较,P<0.05)。结论:MMP-2、MMP-9基因表达上调及TIMP-2基因表达下调参与了创伤弧菌脓毒症的病理生理过程,联用头孢哌酮钠及乳酸左氧氟沙星等抗生素可以下调MMP-2、MMP-9基因表达,上调TIMP-2基因表达,从而减轻创伤弧菌脓毒症临床症状。AIM： To observe the gene expression of matrix metalloprotease 2/9 （MMP-2/9） and tissue inhibitor of metalloproteinase-2 （TIMP-2） in the liver tissues of rats with vibrio vulnificus sepsis and the effects of cefoperazone godium in combination of levofloxacin on the expression of gene MMP2/9 and TIMP-2. METHODS： 110 depuratory grade Sprague-Dawley male rats were randomly divided into three groups, normal control group （CN group, n = 10）, vibrio vulnificus sepsis model groups （VV group, n = 50） and vibrio vulnificus sepsis model treated with cefoperazone godium in combination of levofloxacin （AA groups, n = 50）. The ethological changes were observed in all group rats. The expression of MMP2/9 and TIMP2 mRNA were detected by reverse transcriptive polymerase chain reaction （RT-PCR）. RESULTS： The levels of gene expression of MMP2/9 were markedly up-regulated and TIMP-2 were down-regulated at early time in all VV groups （via CN group, P 〈 0.05）. However, the levels of gene expression of MMP2/9 were down-regulated and TIMP-2 were up-regulated after interruption by antibiotics （via VV group, P 〈 0.05）. CONCLU- SION： The up-regulation of MMP-2/9 and down-regulation of TIMP-2 are associated with the pathophysiological processes of vibrio vulnificus sepsis, the treatment with cefoperazone sodium in combination with levofloxacin may down-regulate the expressions of MMP-2/9 and up-regulate TIMP-2 gene expression in the liver tissue of rats with vibrio vulnificus sepsis, and relieve the clinical symptoms.

关 键 词：创伤弧菌 脓毒症 基质金属蛋白酶 抗生素 

分 类 号：R965.2[医药卫生—药理学]