【摘要】 目的研究外源性基质金属蛋白酶-9(matrix metalloproteinases-9,MMP-9)抑制剂多西环素(Doxycycline)对体外循环(CPB)引起肺损伤的保护作用。方法将20只健康杂种幼犬(体重10～12kg),采用随机数字表法随机分为对照组(n=10)和实验组(n=10);对照组:CPB前后不采取任何肺保护措施;实验组:CPB术前3d每天饲料拌食多西环素(30mg/kg体重)。采用酶联免疫吸附(ELISA)法检测血浆MMP-9浓度;监测两组犬血流动力学和呼吸参数,计算术前和术后肺泡-动脉氧分压差(A-aDO2)和呼吸指数(RI);比色法测定支气管肺泡灌洗液(BALF)髓过氧化物酶(MPO)活性;考马斯亮蓝G-250法测定BALF总蛋白。CPB后,在光学显微镜和电子显微镜下观察肺组织形态学改变;计算肺组织干湿重系数(W/D)。结果两组犬血浆MMP-9浓度随CPB时间延长而显著增高,CBP150min和270min时实验组血浆中MMP-9含量较对照组显著下降(9.45±5.29ng/mlvs.18.66±5.90ng/ml,t=3.664,P=0.005;16.63±2.90ng/mlvs.26.17±5.96ng/ml,t=5.216,P=0.001)。实验组MPO活性,BALF中总蛋白浓度,肺组织W/D,术后A-aDO2和RI均较对照组均明显减低,差异有统计学意义(t=5.622,P=0.000;t=5.081,P=0.001;t=2.266,P=0.050;t=4.927,P=0.001;t=6.679,P=0.000)。肺组织病理和电子显微镜显示实验组损伤明显减轻。结论多西环素通过抑制MMP-9的分泌,降低细胞基底膜的降解,减轻肺泡白细胞浸润和肺水肿,可起到对肺的保护作用。更多还原

【Abstract】 Objective To study the protective effect of exogenous matrix metalloproteinases-9(MMP-9) inhibitor Doxycycline against lung injury during cardiopulmonary bypass(CPB) in dogs. Methods Twenty healthy mongrel puppies(weighed 10 -12 kg) were divided into control group (n=10) and experimental group(n=10) with random number table. In control group, no measure was taken to protect lung before and after CPB. In experimental group, the feeding food was mixed with Doxycycline (30 mg/kg, body weight) daily for three days before operation. Enzyme-linked immunosorbent assay(ELISA) was used to measure the plasma concentration of MMP-9. Hemodynamic and respiratory parameters in two groups were monitored. The preoperative and postoperative alveolar-arterial oxygen partial pressure difference (A-aDO2) and respiratory index(RI) were calculated. The myeloperoxidase(MPO)activity of bronchoalveolar lavage fluid(BALF)was determined by colorimetry. The total protein of BALF was measured by Coomassie Brilliant Blue G-250. After CPB, light microscope and electronic microscope were used to observe the morphological changes of lung tissue. The dry to wet weight index(W/D) was calculated. Results In both groups, the plasma concentrations of MMP-9 increased significantly as the time of CPB prolonged. The plasma MMP-9 at 150 min and 270 min after CPB in experimental group decreased significantly than those in control group (9.45±5.29 ng/ml vs. 18.66±5.90 ng/ml, t=3.664, P=0.005; 16.63±2.90 ng/ml vs. 26.17±5.96 ng/ml, t=5.216, P= 0.001). MPO activity, total protein of BALF, W/D, postoperative A-aDO2 and RI in experimental group decreased significantly than those in control group. There were significant differences between two groups(t=5.622, P=0.000; t=5.081, P=0.001; t=2.266, P=0.050; t=4.927, P=0.001; t=6.679,P=0.000). The lung histopathology and electronic microscope showed that the lung injury reduced significantly. Conclusion Doxycycline plays a role in lung protection by inhibiting the secretion of MMP-9, reducing the degradation of cell basement membrane, pulmonary neutrophil infiltration and pulmonary edema.更多还原