脂氧素受体激动剂BML-111对左向右分流大鼠肺动脉压力影响及其机制的研究

摘要

目的:观察脂氧素受体激动剂BML-111对左向右分流大鼠肺动脉压力的影响及与基质金属蛋白酶(MMP-2、9)及组织途径抑制物(TIMP-1)的关系.方法:将SD大鼠30只分为C组、P组、B组,P组和B组大鼠行建立左颈总动脉-颈外静脉吻合,吻合饲养6周后,B组每天腹腔注射1mg/kg BML-111连续4周,P组每天腹腔注射等量生理盐水.实验测量指标:各组大鼠体重增长速度、平均肺动脉压力、右心室收缩压、右室(RV)/(左室LV+室间隔S)、肺小动脉中膜厚度百分比、肺血管纤维化程度比、肺组织MMP-2、MMP-9、TIMP-1的水平.结果:P组、B组与C组相比平均肺动脉压力、右心室收缩压、RV/(LV+S)、肺小动脉中膜厚度百分比、肺血管纤维化程度比、肺组织MMP-2、MMP-9、TIMP-1的水平均高于P组,体重增长速度低于C组(P＜0.05);B组与P组相比,平均肺动脉压力、右心室收缩压、肺小动脉中膜厚度百分比、肺血管纤维化程度比、肺组织MMP-2、MMP-9、TIMP-1低于P组,体重高于P组(P＜0.05).结论:脂氧素受体激动剂BML-111减轻肺动脉高压的作用机制可能与降低MMP-2、9和TIMP-1的表达有关.%Objective :To observe the the effect of lipoxin receptor agonist BML-111 on pulmonary arterial hypertension of left to right shunt rats and the relationship with matrix metalloproteinase-2 ,9 (MMP-2 ,9) and tissue inhibitors of metalloproteinases-1 (TIMP-1). Methods :30SD rats were selected and randomly divided into three groups : C group , P group and B group , Both the P group and B group processed left common carotid artery-external jugular vein shunt, six weeks later, B group performed intraperitoneal injection of BML-111 llmg/kg o d while P group received same volume of saline , After four weeks , all the rats were selected to performed the experiment . The observation contain the growth speed of body weight , mean pulmonary arterial pressure , right ventricle systolic pressure , the weight ratio of right ventricle to left ventricle plus septal , the ratio of medial hypertrophy of small pulmonary arteries and fibrosis , the expression of MMP-2、MMP-9、TIMP-1 in pulmonary tissue . Results :the P group and B group had higher mean pulmonary arterial pressure , right ventricle systolic pressure , the weight ratio of right ventricle to left ventricle plus septal, the ratio of medial hypertrophy of small pulmonary arteries and fibrosis , MMP-2 ,9 , TIMP-1 and lower growth of body weight compared with C group (P<0 .05). The B group had lower mean pulmonary arterial pressure , right ventricle systolic pressure, higher growth of body weight, the ratio of medial hypertrophy of small pulmonary arteries and fibrosis , MMP-2 ,9 , TIMP-1 and higher growth speed of body weight, compared with P group(P<0 .05) . Conclusion :Lipoxin receptor agonist BML-111 can ameliorate pulmonary arterial hypertension of left to right shunt of rats , partly reason may be attribute to the reduction the level of MMP-2 ,9 and TIMP-1 of pulmonary tissue .