Galectin-3拮抗剂改良柑橘果胶对肺动脉高压大鼠的作用

Effect of Galectin-3 antagonist modified citrus pectin on pulmonary hypertension in rats

目的通过使用Galectin-3特异性配体拮抗剂改良柑橘果胶(modified citrus pectin,MCP)对肺动脉高压(PAH)动物模型进行干预,探讨MCP对PAH的治疗效果。方法SD大鼠随机分为对照组、野百合碱(MCT)组、MCT+生理盐水组(MCT+saline)、MCT+MCP组。MCT组通过皮下注射MCT构建PAH模型,MCT+MCP组在注射MCT后使用MCP溶液灌胃。MCT+saline组在注射MCT后使用生理盐水灌胃。对照组在常规条件下饲养。对各组大鼠进行血流动力学、心脏形态、组织学及蛋白质表达等方面的检测。同时还检测PAH患者与健康对照者血浆中的Galectin-3水平。结果PAH患者血浆Galectin-3水平较健康受试者显著升高(P<0.05)。MCP能显著降低MCT诱导的PAH大鼠的肺动脉平均压、右室收缩压及大鼠右室/(左室+室间隔)重量比。PAH大鼠肺动脉血管重构明显,MCP能显著减轻PAH大鼠肺动脉血管重构,但MCP并不能减轻Galectin-3在肺血管外膜中的表达。MCP能显著减少PAH大鼠肺组织中的collagenⅠ、collagenⅢ蛋白含量,但MCP并不能减轻Galectin-3蛋白在PAH大鼠肺组织中的表达。结论MCP能够减低PAH大鼠的肺动脉压力,显著减轻PAH大鼠的肺动脉血管重构,表明Galectin-3在PAH的发病机制中起重要作用,靶向干预Galectin-3可能为PAH治疗提供新的思路。

Objective To investigate the therapeutic effects of modified citrus pectin(MCP)on pulmonary arterial hypertension(PAH)by using a Galectin-3-specific ligand antagonist in an animal model of PAH.Methods Sprague-Dawley(SD)rats were randomly divided into four groups:Control,Monocrotaline(MCT),MCT+Saline,and MCT+MCP.PAH was induced in the MCT group by subcutaneous injection of monocrotaline,while the MCT+MCP group received MCP solution orally after MCT injection.The MCT+Saline group received saline orally after MCT injection.Rats in the Control group were maintained under standard conditions.Various parameters including hemodynamics,cardiac morphology,histology,and protein expression were evaluated in each group.Additionally,Galectin-3 levels in plasma were measured in PAH patients and healthy controls.Results Plasma Galectin-3 levels were significantly elevated in PAH patients compared to healthy controls.MCP significantly reduced mean pulmonary artery pressure,right ventricular systolic pressure,and right ventricle/(left ventricle+septum)weight ratio in MCT-induced PAH rats.MCP significantly alleviated pulmonary arterial vascular remodeling in PAH rats,although it did not reduce Galectin-3 expression in the pulmonary vascular adventitia.MCP significantly reduced collagen I and collagen III protein content in lung tissues of PAH rats but did not alleviate Galectin-3 protein expression in lung tissues.Conclusion MCP effectively reduces pulmonary artery pressure and alleviates pulmonary arterial vascular remodeling in PAH rats,suggesting that Galectin-3 plays an important role in the pathogenesis of PAH.Targeted intervention against Gal-3 may provide a new therapeutic approach for PAH treatment.