文章摘要
王常田,程晓峰,张雷,吴海卫,许飚,李德闽.多西环素对大鼠体外循环后肺内MMP-9和TIMP-1活性和基因表达的影响[J].南京医科大学学报,2014,(1):
多西环素对大鼠体外循环后肺内MMP-9和TIMP-1活性和基因表达的影响
Effect of doxycycline on MMP-9 and TIMP-1 activity and mRNA expression in lung after cardiopulmonary bypass with a rat model
投稿时间:2013-07-02  修订日期:2013-07-02
DOI:10.7655/NYDXBNS201401022
中文关键词: 基质金属蛋白酶-9,组织基质金属蛋白酶抑制剂-1,多西环素,体外循环
英文关键词: Matrix Metalloproteinase-9,Tissue inhibitor of metalloproteinases -1, Doxycycline, Cardiopulmonary Bypass
基金项目:
作者单位E-mail
王常田 中国人民解放军南京军区南京总医院心胸外科 wct35037@163.com 
程晓峰 中国人民解放军南京军区南京总医院心胸外科  
张雷 中国人民解放军南京军区南京总医院心胸外科  
吴海卫 中国人民解放军南京军区南京总医院心胸外科  
许飚 中国人民解放军南京军区南京总医院心胸外科  
李德闽 中国人民解放军南京军区南京总医院心胸外科 dr.demin@126.com 
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中文摘要:
      目的:探讨多西环素对大鼠体外循环后肺内基质金属蛋白酶-9和组织基质金属蛋白酶抑制剂-1活性和基因表达的影响。方法:健康雄性SD大鼠36只随机分为对照组(A组)、体外循环组(B组)和治疗组(C组),分别于手术结束时(T1)和手术结束后6小时(T2)收集支气管肺泡灌洗液(BALF)和肺组织标本。Western-blot法测定BALF中MMP-9和TIMP-1的蛋白活性,RT-PCR法测定肺组织MMP-9和TIMP-1mRNA的表达。结果:治疗组大鼠肺组织水肿减轻,BALF的中性粒细胞减少;CPB组BALF中MMP-9活性明显升高,CPB后6小时表达最强,治疗组MMP-9活性较CPB组有明显下降,TIMP-1的活性在CPB组和治疗组于CPB结束后呈较弱的增强趋势,两组间相同时间点的表达差异不明显;CPB组和治疗组MMP-9mRNA表达增强,但治疗组MMP-9mRNA的表达在相应时间点较治疗组下降;TIMP-1mRNA在治疗组表达增强,且T2时间点显著增强;MMP-9/TIMP-1mRNA在CPB组和治疗组均有显著增大,但治疗组中T2时间点组MMP-9/TIMP-1mRNA比值较CPB组明显下降。结论:CPB可以引起大鼠术后肺内MMP-9的活性和基因表达增强,导致术后早期肺内MMP-9/TIMP-1mRNA表达失衡,多西环素可以抑制CPB后大鼠肺组织内MMP-9蛋白水平和mRNA的表达,还可能上调TIMP-1的表达而间接抑制MMP-9mRNA表达,改善MMP-9/TIMP-1的比例失衡。
英文摘要:
      Objective:This study was aimed to investigate the effect of doxycycline on the activity and mRNA expression of MMP-9 and TIMP-1 in CPB by a rat model. Methods: Male Sprague-Dawley rats were randomly divided into 3 groups (n=12, respectively): sham group, CPB group, and CPB Dox group. The rats were executed at the termination of CPB (T1), 6h after termination of CPB (T2) respectively. BALF and lung tissues were harvested at T1 and T2. The lung wet/dry ratio (W/D) was measured. Neutrophil in BALF was counted. The activity of MMP-9 and TIMP-1 was detected by Western-blot analysis. The expression of MMP-9 and TIMP-1 in lung tissue was detected by RT-PCR. Results: The edema of lung tissue significantly reduced in CPB Dox group compared with CPB group, and neutrophils were less than CPB group. The activity of MMP-9 by Western-blot in CPB Dox group decreased significantly compared with CPB group and the activity of TIMP-1 was a weaker increasing trend in CPB and CPB Dox group. The expression of MMP-9 mRNA by RT-PCR was significantly increased after CPB in CPB and CPB Dox group, but significantly decreased at T2 time point in CPB Dox group. The ratio of MMP-9/TIMP-1 was significantly increased in CPB and CPB Dox group, but in CPB Dox group was significantly lower than in CPB group at T2 time. Conclusions: CPB could induce the activity and mRNA of MMP-9 of lung increased, causing the ratio of MMP-9/TIMP-1 imbalanced severely at the early postoperative. Doxycycline could inhibit the expression of MMP-9 activity and mRNA in rat lung tissue after CPB, and might increase the expression of TIMP-1 in rats after CPB, and inhibit the expression of MMP-9mRNA indirectly, which could improve the ratio of MMP-9/TIMP-1 imbalance.
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