琥珀酸促进野百合碱诱导的心肺小动脉间质纤维化

发布时间：2018-04-29 16:40

  本文选题：肺动脉高压 + 早期纤维化　； 参考：《南京医科大学学报(自然科学版)》2017年09期

【摘要】：目的:探讨琥珀酸能否促进野百合碱诱导的肺动脉高压大鼠模型心肺小动脉间质纤维化,并初步探索其机制。方法:4~5周龄健康雄性SD大鼠30只,体重120~180 g,随机分为对照组、野百合碱(monocrotaline,MCT)组、野百合碱和琥珀酸(succinic acid,SUC)联合使用组(MCT+SUC组),每组10只。MCT组和MCT+SUC组予腹腔注射MCT建造大鼠肺小动脉高压模型,MCT+SUC组继续予SUC干预4周。4周后,利用漂浮导管检测平均肺动脉压(mean pressure of pulmonary artery,mPAP)、右心室收缩压(right ventricular systolic pressure,RVSP)、肺动脉收缩压(systolic blood pressure,SBP)和肺动脉舒张压(diastolic blood pressure,DBP)等血流动力学指标。安乐死后取组织测定右室肥厚指数,行HE染色观察心脏和肺组织小动脉的肌化情况,Masson、天狼星红染色观测心脏和肺小动脉周围纤维化情况,Western blot和免疫组织化学检测心脏组织血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)、血小板衍生因子-BB(platelet derived growth factor,PDGF-BB)和成纤维细胞生长因子-2((fibroblast growth factor 2,FGF2)等蛋白表达水平。结果:MCT组、MCT+SUC组大鼠均表现食量减少、倦卧等症状,MCT+SUC组大鼠出现唇周紫绀、气促等表现较早。MCT+SUC组RVSP、mPAP、肺动脉SBP和肺动脉DBP、右室肥厚指数、心肺小动脉中层增厚程度均明显大于MCT组(P均0.05)。HE染色显示,MCT组心肺小动脉轻度增厚,MCT+SUC组心脏小动脉壁增厚程度较MCT组更加明显,局部心肌组织炎性细胞浸润增加。天狼星红染色与Masson染色结果显示,MCT+SUC组心肺小动脉周围间质内胶原纤维异常增生,MCT组心肺小动脉周围未见胶原纤维异常增生。Western blot和免疫组织化学结果显示,MCT+SUC组和MCT组肺组织AngⅡ、PDGF-BB、FGF2蛋白表达水平变化与对照组相比均有不同程度的升高,MCT+SUC组较MCT组上升水平更加明显。结论:SUC可以促进MCT诱导的心肺小动脉间质纤维化的形成,其机制可能是上调FGF2和PDGF-BB等促纤维化的细胞因子,AngⅡ表达升高,导致心肺小动脉间质纤维化的形成。
[Abstract]:Aim: to investigate whether succinic acid can promote the interstitial fibrosis of pulmonary arterioles induced by monocrotaline in rats with pulmonary hypertension and to explore its mechanism. Methods Thirty healthy male Sprague-Dawley rats of 5 weeks old, weighing 120,180 g, were randomly divided into control group and monocrotaline monocrotaline (MCTT) group. Monocrotaline and succinic acidosis suc) were used in each group with 10 rats in each group. MCT group and MCT SUC group were given intraperitoneal injection of MCT to construct pulmonary arteriolar hypertension in rats. The SUC group was treated with SUC for 4 weeks. The mean pressure of pulmonary arterial pressure (mean pressure of pulmonary), right ventricular systolic pressure (RVSPV), systolic blood pressure (SBP) and pulmonary diastolic blood pressure (DBP) were measured by floating catheter. The right ventricular hypertrophy index was measured after euthanasia. He staining was used to observe the muscularization of the arterioles in heart and lung tissue, Sirius red staining was used to observe the fibrosis around the heart and pulmonary arterioles, and immunohistochemistry was used to detect angiotensin 鈪，

本文编号：1820734