肺动脉灌注含巴马司他肺保护液对体外循环犬肺的保护作用及机制探讨

Protective effect and mechanism of continuous pulmonary artery perfusion with batimastat solution on dogs' lung injury during cardiopulmonary bypass

目的探讨肺动脉持续灌注含巴马司他的肺保护液对体外循环中犬肺的保护作用,并探讨其机制。方法16只杂种犬,随机分为A、B组,各8只。常规建立体外循环,A组用不含巴马司他的肺保护液,B组用含巴马司他30mg/kg的肺保护液,流量30ml/(kg.min)灌注肺动脉。记录两组犬手术前后血气分析结果,计算肺泡—动脉氧分压差(A-aDO2)和呼吸指数(RI)。分别于转流前、停体外循环即刻、转流后1h、转流后2h采集静脉血,比色法测定血浆髓过氧化物酶(MPO)活性。体外循环结束后,取左上肺标本,光镜和电镜下观察肺组织形态学改变;取小块左肺组织称重烘烤计算肺组织湿重系数(W/D)。支气管肺泡灌洗液离心取上清液(BALF),ELISA法测MMP-9浓度,考马斯亮蓝G-250法测总蛋白。结果转流后B组A-aDO2和RI明显低于对照组(P<0.05)。两组血浆MPO活性相比,B组明显低于A组(P<0.05),。B组肺湿干比重(W/D)、BALF总蛋白含量和MMP-9含量均低于A组(P均<0.05)。肺组织病理显示肺灌注组损伤明显减轻。结论肺动脉持续灌注含巴马司他的肺保护液通过降低血MMP-9浓度和减少中性粒细胞集聚来降减轻体外循环中的肺损伤。

Objective To investigate the protective effect of pulmonary artery infusion with matrix metalloproteinasc inhibitor batimastat solution on lung injury induced by CPB. Methods 16 healthy mongrel puppies were randomly divided into A and B groups. The pulmonary perfusion solution with non-batimastat was used in group A and the pulmonary perfusion solution containing hatimastat 30 mg/kg was used in group B. Hemodynamie and respiratory parameters were monitored, then A-aDO2 and RI were calculated. The plasma of myeloperoxidase （MPO） activities were measured by colorimetry in four moments in the course of the operation. After the end of CPB, fight and electronie microscopes were used to observe the morphological changes of lung tissue. A small piece of left lung tissue was taken to weigh and bake to calculate the wet weight index （W/D）. BALF concentrations of MMP-9 were measured by ELISA, and the total proteins of BALF were measured by Coomassie Brilliant Blue G-P30. Results After cardiopulmonary bypass, the A-aDO2 and RI of batimastat peffusion group were significantly lower than the control group （ P 〈 0.05 ）. There were statistically significant difference between two plasma MPO activity overall （ P 〈 0.05）, and batimastat lung pedusion group was significantly lower than the control group. The lung wet dry weight （ W/D）, total protein in BALF and MMP-9 concentrations of batimastat perfusion group was lower than the control group （ P 〈 0.05 ）. And the pathological changes of lung tissue were significantly improved in the batimastat lung perfusion group. Conclusion Pulmonary artery infusion with batimastat protective solution can obviously reduce lung injury after cardiopulmonary bypass by reducing blood concentrations of MMP-9 and reducing the infiltration of neutrophils .