基质金属蛋白酶-9抑制剂巴马司他对心肺转流急性肺损伤的保护作用  

Protective role of MMP-9 inhibitor batimastat in acute lung injury after cardiopulmonary bypass

作　　者：葛圣林[1] 龚文辉[3] 张成鑫[1] 张雷[2] 韩培华[1] 张胜权[4] 冯俊波[1] 周德存[5] 

机构地区：[1]安徽医科大学第一附属医院心脏血管外科,合肥230022 [2]安徽医科大学第一附属医院麻醉科,合肥230022 [3]安徽医科大学第二附属医院心胸外科 [4]安徽医科大学分子生物学实验室 [5]安徽省立新安医院心胸外科

出　　处：《中华外科杂志》2010年第1期57-61,共5页Chinese Journal of Surgery

基　　金：基金项目：安徽省自然科学基金资助项目（070413070）（志谢感谢安徽大学医学分子生物学实验室,第一附属医院麻醉科、病理科和动物实验室的大力支持.此外还要感谢占红英灌注师在CPB灌注方面给予的技术帮助）

摘　　要：目的研究外源性基质金属蛋白酶-9（MMP-9）抑制剂巴马司他在心肺转流急性肺损伤中的保护作用。方法30只健康杂种幼犬随机分为对照组、低剂量组和高剂量组。低剂量组术前连续3d每天腹腔注射巴马司他10mg／kg，高剂量组术前连续3d每天腹腔注射巴马司他30mg／kg。分别计算术前和术后肺泡-动脉氧分压差（A—aDO2）和呼吸指数（RI）。从手术前开始计时，分别于0、60、120和270min时采集静脉血样，酶联免疫吸附法测血浆MMP-9浓度，RT-PCR法测定血MMP-9mRNA表达变化。比色法测定支气管肺泡灌洗液（BALF）髓过氧化物酶活性，明胶酶谱法测定BALFMMP-9活性。计算肺湿／干质量比。光镜和电镜下观察肺组织形态学改变。结果270min时高剂量组血浆MMP-9浓度（17．36±1．18）μg/L，低于对照组的（30．47±2．22）μg/L（P〈0．05）。高剂量组术后A—aDO2和RI较对照组明显改善（P〈0．05），高剂量组肺湿／干质量比（2．8±0．5）较对照组（4．7±0．6）明显减低（P〈0．05），且肺组织的病理改变显著减轻；但三组间血MMP-9mRNA表达无明显差异（P〉0．05）。结论巴马司他通过降低MMP-9的浓度及活性，减轻细胞基底膜的降解，减轻肺泡白细胞浸润和肺水肿，起到肺保护的作用。Objective To investigate the protective effect of exogenous inhibitor of matrix metalloproteinases-9 （MMP-9）, batimastat, in the lung injury induced by cardiopulmonary bypass （CPB） in dogs. Methods Thirty healthy mongrel puppies were randomly divided into 3 groups：control group, lowdose group [ batimastat 10 mg/（ kg · d） for 3 days before operation ] and high-dose group [ batimastat 30 mg/（kg · d） for 3 days before operation] .The off-pump puppies＇ model of acute lung injury was established, and hemodynamic and respiratory parameters were monitored. The preoperative and postoperative alveolar-arterial oxygen difference （A-aDO2 ） and respiratory index （RI） were calculated. From the beginning of surgery, blood samples were taken at the time 0, 60, 120, and 270 min. Plasma concentrations of MMP-9 were measured by ELISA, and blood MMP-9 mRNA expressions were determined by RT-PCR. The myeloperoxidase （MPO） activity of centrifugal bronchoalveolar lavage fluid were measured by Colorimetry. And MMP-9 activity was determined by Gelatin zymography. Light and electronic microscope were used to observe the morphological changes of lung tissue. A small piece of left lung tissue was taken, weighed and baked to calculate the wet weight （W/D） index. Results After cardiopalmouary bypass, the concentrations of MMP-9 and mRNA expressions of the control group were increased significantly, and lung injury was apparent. At 270 rain, the MMP-9 plasma concentration of high-dose group （17.36± 1.18） μg/L was significant reducing than control group （30. 47 ± 2.22） μg/L （ P 〈 0. 05 ）. After operation, A-aDO2 and RI of high-dose group were significantly improved than control group （ P 〈 0. 05 ）. The W/D index of thehigh-dose group （2.8 ± 0. 48 ） was significantly lower than that of control group （4. 7 - 0. 6） （ P 〈 0. 05 ）. And the pathological changes of lung tissue were significantly improved in the high-dose group. However, there was no significant difference in

关 键 词：心肺转流术 呼吸窘迫综合征 成人 基质金属蛋白酶9 

分 类 号：R654.2[医药卫生—外科学] R655.3[医药卫生—临床医学]