多西环素对大鼠体外循环后肺内MMP-9与TIMP-1.docVIP

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 王常田　程晓峰　张雷　吴海卫　许飚　李德闽 南京军区南京总医院心胸外科 210002 【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Western-blot法测定BALF中MMP-9TIMP-1的蛋白活性RT-PCR法测定肺组织MMP-9TIMP-1mRNA的表达BALF的中性粒细胞CPB组BALF中MMP-9活性明显升高，CPB后6小时表达最强，组MMP-9活性较CPB组有明显下降-1的活性在CPB组和组于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mRNA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均有显著增大，T2时间点组MMP-9/TIMP-1mRNA比值较CPB组明显下降术后早期肺内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TIMP-1的表达而间接抑制MMP-9mRNA表达改善MMP-9/TIMP-1比例失衡 【关键词】基质金属蛋白酶-9，组织基质金属蛋白酶抑制剂 Effect of doxycycline on MMP-9 and TIMP-1 activity and mRNA expression in lung after cardiopulmonary bypass with a rat model WANG Changtian ,CHENG Xiaofeng, ZHANG Lei, WU Haiwei, XU Biao, LI Demin Department of Thoracic and Cardiovascular Surgery ,Nanjing General Hospital of Nanjing Command, Nanjing 210002 【Abstract】　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 significan