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

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/kgBML-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。

The effect and mechanism of lipoxin receptor agonist BML-111 on of pulmonary arterial pressure of left to right shunt rats model

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 11mg/kg·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.