Protective Role Of Mmp-9 Inhibitor Batimastat In Acute Lung Injury After Cardiopulmonary Bypass

Objective: To investigate the protective effect of exogenous inhibitor of matrix metalloproteinases-9 (MMP-9), Batimastat, in the lung injury induced by CPB in dogs.Methods: Thirty healthy mongrel puppies were randomly divided into 3 groups: control group, low-dose group (Batimastat 10mg/kg·d ip for three days before operation) and high-dose group (Batimastat 30mg/kg·d ip for three 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 A-aDO2 and RI were calculated. Plasma concentrations of MMP-9 were measured by ELISA, and blood MMP-9 gene expressions were determined by RT-PCR. The myeloperoxidase (MPO) activity of centrifugal bronchoalveolar lavage fluid (BALF) 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 index (W/D).Results: 1 The concentration of plasma MMP-9 in three groups increased with time, and the MMP-9 plasma concentration of high-dose group at 270 min was was significantly lower than the other groups (P <0.05). The mean levels of MMP-9 plasma in low-dose group was lower than the control group, but there was no statistically significant difference (P> 0.05) between them. 2 Three groups of serum MMP-9 gene expression tended to increase significantly with time (P <0.05), but there were no significant differences in the expression of the three groups (P> 0.05).3 The MMP-9 activity in bronchoalveolar lavage fluid of high-dose group significantly decreased compared with the control group, and low-dose group wee less significantly decreased than the high dose group.4 The MPO activity in high-dose group was lower than the control group (P <0.05), the MPO activity in low-dose group was also decreased, but there is no statistically significant difference (P> 0.05).5 Lung tissue water content was indicated with the lung WET/DRY weight ratio. The W/D value of high-dose group ( 2.8±0.5 ) was statistically significant lower than that of control group(4.7±0.6) and low dose group(4.4±1.1) (P <0.05).6 The A-aDO2 and RI of three groups preoperative was no significant difference (P> 0.05). The A-aDO2 and RI in the control group was highest, and that in the high-dose group was lowest after operation (P <0.05).7 There was the most serious in lung tissue of control group and the lightest serious in lung tissue of the high-dose group by light and electron lesion microscopy.Conclusion Batimastat plays a role in the protection of the lung injury of CBP by reducing the concentration and activity of MMP-9, the degradation of the cell membrane and pulmonary neutrophil infiltration and reduction of pulmonary edema.