机构地区:[1]内蒙古科技大学包头医学院,内蒙古包头014040 [2]中国医学科学院,北京协和医学院,阜外医院肺血管医学重点实验室,心血管疾病国家重点实验室,国家心血管病中心,北京100037 [3]包头医学院第二附属医院心内科,内蒙古包头014030 [4]浙江大学医学院附属邵逸夫医院全科医学科,杭州310016 [5]衢州市柯城区人民医院,浙江衢州324000
出 处:《中国比较医学杂志》2023年第10期1-7,共7页Chinese Journal of Comparative Medicine
基 金:国家自然科学基金(82170408);北京市自然科学基金(7222142);北京市自然科学基金面上项目(7222142);心血管疾病国家重点实验室重点项目(2022ZD-05)。
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患者,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(monocrotaline, MCT)组(50 mg/kg)模拟特发性肺动脉高压(n=8);颈部动静脉分流手术+MCT组(50 mg/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周进行超声心动图检测、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(left ventricular internal diame, LVID;d)未降低,左心射血分数(ejection fraction, 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(maximal ventricular pressure rising rate, dp/dt Max)和等容舒张期心室内压下降最大速率(maximal rate of decrease of ventricular pressure, dp/dt Min)均低于单纯MCT组(P<0.05)。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。Objective The prognosis of patients with left-to-right shunt congenital heart disease-associated pulmonary hypertension is significantly better than that of patients with idiopathic pulmonary hypertension,but the specific mechanism is unclear.The purpose of this study was to establish 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 terms of pulmonary vascular remodeling and cardiac remodeling.Methods Male SD rats were divided into three groups:control group(n=8),monocrotaline(MCT)group(50 mg/kg)to simulate idiopathic pulmonary hypertension(n=8),and cervical arteriovenous shunt surgery+monocrotaline(MCT)group(50 mg/kg)to simulate left-to-right shunt congenital heart disease with pulmonary hypertension(n=8).Three weeks after establishment of the model,echocardiography,left and right cardiac catheter pressure measurements,and lung histopathological staining were performed to compare cardiac and pulmonary phenotypes of the rats.Results Compared with the control group,no significant difference was found between the MCT and the operation+MCT groups in terms of the right ventricular hypertrophy,right ventricular dysfunction,mean pulmonary artery pressure,pulmonary vascular remodeling,or other indicators at 3 weeks after the operation.However,many indexes related to left heart in rats of the operation+MCT group were significantly better than those in the simple MCT group.Compared with that in the control group,the left ventricular lumen diameter(and left ventricular ejection fraction)in the operation+MCT group did not decrease in the diastolic period.The maximum rate of increase in right ventricular internal pressure and the maximum rate of decrease in left ventricular internal pressure in the operation+MCT group were lower than that in the simple MCT group.Conclusions Left-to-right shunt surgery cannot change MCT-induced pulmonary hypertension or right heart remodeling,but can produce left hea
关 键 词:先天性心脏病相关肺动脉高压 特发性肺动脉高压 肺血管重构 动物模型
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