脂氧素受体激动剂BML-111对左向右分流型肺动脉高压大鼠作用的影响

Effect of lipoxin receptor agonist BML-111 on rats with pulmonary hypertension induced by left-to-right shunt

目的观察脂氧素受体激动剂BML-111对肺动脉高压大鼠肺动脉压力和肺组织炎症的影响。方法选择SD大鼠30只,随机分为三组:C组、PH组、B组,PH组和B组大鼠行建立左颈总动脉-颈外静脉吻合加左侧股动脉-股静脉吻合,吻合饲养六周后,PH组每天腹腔注射生理盐水,B组每天腹腔注射1mg·kg-1·d-1BML-111连续四周,C组每天腹腔注射等量生理盐水。实验测量指标: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、小动脉肌化程度、新生内膜厚度百分比、肺组织匀浆炎症因子IL-6、TNF-α、MCP-1的水平。结果 PH组和B组平均肺动脉压力、右心室收缩压、RV/(LV+S)、肺小动脉中膜厚度百分比、小动脉肌化程度、新生内膜厚度百分比高于C组(P<0.05),PH组和B组大鼠肺组织匀浆IL-6、TNF-α、MCP-1的含量高于C组(P<0.05);B组平均肺动脉压力、右心室收缩压、肺小动脉中膜厚度百分比、新生内膜厚度百分比低于PH组(P<0.05),B组大鼠肺组织匀浆IL-6、TNF-α、MCP-1均低于PH组(P<0.05)。结论脂氧素受体激动剂BML-111可减轻左向右分流型肺动脉高压大鼠肺动脉压力,其机制可能与减轻肺周围组织炎症反应有关。

Objective To observe the effect of BML-111 on pulmonary arterial pressure and inflammation of rats with pulmonary hypertension induced by left-to-right shunt. Methods Thirty SD rats were randomly divided into three groups： C group, PH group and B group. Both PH group and B group applied left common carotid artery-ex- ternal jugular vein shunt and left femoral artery-vein shunt. Six weeks later, rats in B group received intraperitoneal in- jection of BML-111 1 mg. kg-~. dl, while those in PH group received saline injection for four weeks. The rats in C group were treated by intraperitoneal injection of saline. The MPAP, RVSP, RV/（LV＋S）, the ratio of media thickness of pulmonary arterioles, distal arteriole muscularization and the count of neointimal proliferation, and the level of IL-6, TNF-ct, MCP-1 of pulmonary tissue were compared between the three groups. Results Compared with C group, the PH ~oup and B group has significantly higher levels of MPAP, RVSP, RV/（LV＋S）, the ratio of media thickness of pulmonary arterioles, distal arteriole muscularization and the count of neointimal proliferation, and significantly high- er levels of IL-6, TNF-c~, MCP-1 in pulmonary tissue （/~〈0.05）. Compared with B group, the PH group has higher levels of MPAP, RVSP, the ratio of media thickness of pulmonary arterioles and the count of neointimal proliferation, IL-6, TNF-a, MCP-1 in pulmonary tissue （P 〈 0.05）. Conclusion BML-111 can ameliorate pulmonary arterial hy- pertension. The mechanism might be attributed to the reduction of the inflammation of pulmonary tissue.