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 [CM(159mm]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. Key words: Cardiopulmonary bypass; Acute lung injury; Matrix metalloproteinase; Doxycycline; Lung protection

Citation： GONG Wenhui,GE Shenglin,ZHANG Chengxin,et al .. Effect of Matrix Metalloproteinase9 Inhibitor on Lung Injury during Cardiopulmonary Bypass in Dogs. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2010, 17(1): 36-40. doi: Copy