Baotou Medical College
National Natural Science Foundation of China (82170408); Beijing Natural Science Foundation (7222142)
【摘要】目的：左向右分流型先心病相关肺动脉高压患者预后要显著好于特发性肺动脉高压，但具体机制不清。本项目旨在制作特发性肺动脉高压与先心病合并肺动脉高压大鼠模型，比较两种模型在肺血管重构和心脏重构方面的异同。方法：雄性SD大鼠分成3组：对照组（n=8），单纯野百合碱（MCT）组（50mg/kg）模拟特发性肺动脉高压(n=8)；颈部动静脉分流手术 MCT组（50mg/kg）模拟左向右分流型先心病合并肺动脉高压(n=8)。造模后3周行超声心动图检测、左右心导管测压和肺组织病理学染色，比较大鼠心肺表型。结果：与对照组相比，单纯MCT组和手术 MCT组大鼠在术后3周右室肥厚、右室功能障碍，平均肺动脉压、肺血管重构等多项指标上均无明显差异。但在左心相关多项指标上，手术 MCT组大鼠显著优于单纯MCT组。与对照组相比，手术 MCT组大鼠舒张期左室腔径（LVID;d）未降低，左心射血分数(EF%)未升高；手术 MCT组大鼠右心等容收缩期心室内压上升最大速率(MAX dp/dt)和等容舒张期心室内压下降最大速率(MIN dp/dt)均低于单纯MCT组。结论：左向右分流手术不能改变MCT诱导产生的肺动脉高压和右心重构，但能够产生左心代偿作用，可能有利于患者预后。本项目动物模型模型为研究特发性肺动脉高压及先心病相关肺动脉高压的不同病理机制建立基础。
【Abstract】Objective: The prognosis of patients with left-to-right shunt congenital heart disease associated pulmonary hypertension is significantly better than that of idiopathic pulmonary hypertension, but the specific mechanism is unclear. The purpose of this project is to make a rat model of idiopathic pulmonary hypertension and congenital heart disease with pulmonary hypertension, and compare the similarities and differences between the two models in pulmonary vascular remodeling and cardiac remodeling. Methods: Male SD rats were divided into three groups: control group (n=8), monocrotaline (MCT) group (50mg/kg) to simulate idiopathic pulmonary hypertension (n=8); Cervical arteriovenous shunt surgery monocrotaline (MCT) group (50mg/kg) simulated left to right shunt congenital heart disease with pulmonary hypertension (n=8). Three weeks after the establishment of the model, echocardiography, left and right cardiac catheter pressure measurement and lung histopathological staining were performed to compare the cardiac and pulmonary phenotypes of the rats. Results: Compared with the control group, there was no significant difference between the MCT group and the operation MCT group in the right ventricular hypertrophy, right ventricular dysfunction, mean pulmonary artery pressure, pulmonary vascular remodeling and other indicators 3 weeks after operation. But in many indexes related to left heart, the rats in the operation MCT group were significantly better than those in the simple MCT group. Compared with the control group, the left ventricular lumen diameter (LVID; d) and left ventricular ejection fraction (EF%) in the operation MCT group did not decrease in the diastolic period; The maximum rate of increase of right ventricular internal pressure (MAX dp/dt) and the maximum rate of decrease of left ventricular internal pressure (MIN dp/dt) in the operation MCT group were lower than those in the simple MCT group. Conclusion: Left to right shunt surgery can not change MCT-induced pulmonary hypertension and right heart remodeling, but can produce left heart compensation, which may be beneficial to the prognosis of patients. The animal model of this project establishes the basis for studying the different pathological mechanisms of idiopathic pulmonary hypertension and pulmonary hypertension associated with congenital heart disease.