用野百合碱诱导的肺动脉高压雄性大鼠的右心室结构与功能变化  

Structural and functional changes of right ventricle in male rats with monocrotaline-induced pulmonary arterial hypertension

作　　者：李慧茹 谢新 华玉美多 李占强[1] 芦殿香[1,3] LI Huiru;XIE Xin;Huayumeiduo;LI Zhanqiang;LU Dianxiang(Research Center for High Altitude Medicine,Qinghai University,Key Laboratory of Ministry of Education forHigh Altitude Medicine,Laboratory for High Altitude Medicine in Qinghai Province,Key Laboratory of Applicationand Foundation for High Altitude Medicine Research in Qinghai Province(Qinghai-Utah Joint Research Key Labfor High Altitude Medicine),Qinghai University,Xining 810001,China;College of Eco-environmental Engineering,Qinghai University,Chengdu 610081,China;Affiliated Hospital of Chengdu University,Xining 810016,China)

机构地区：[1]青海大学高原医学研究中心,高原医学教育部重点实验室,青海省高原医学实验室,青海省高原医学应用基础重点实验室(青海-犹他高原医学联合重点实验室),西宁810001 [2]青海大学生态环境工程学院,成都610081 [3]成都大学附属医院,西宁810016

出　　处：《中国高原医学与生物学杂志》2024年第2期83-89,共7页Journal of Chinese High Altitude Medicine & Biology

基　　金：国家自然科学基金(82060786)。

摘　　要：目的观测用野百合碱(monocrotaline,MCT)诱导的肺动脉高压(pulmonary arterial hypertension,PAH)雄性大鼠的右心室(right ventricle,RV)结构与功能变化情况,以进一步验证其诱发肺动脉高压的机制。方法将SD雄性大鼠随机分为对照组、模型组,每组12只。模型组大鼠接受单次40 mg·kg-1的MCT皮下注射。注射MCT第0周、2周、3周、4周末时检测超声心动图,评价右心室功能和右心室-肺动脉(RV-PA)耦合情况。注射MCT第4周时采用右心导管术检测大鼠平均肺动脉压(mPAP),取脏器并称重,计算脏器系数及右心室肥厚指数(RVHI);采用HE染色法观察肺小动脉病理形态学变化,计算管腔面积占血管总面积的百分比(WA%)、管壁厚度占血管外半径的百分比(WT%);采用HE、Masson染色法观察右心室心肌细胞的肥大程度和纤维化程度。结果与0周相比,2周时,模型组大鼠右心室游离壁厚度(RVFW)增加、平均肺动脉压(mPAP)升高(P<0.05),三尖瓣环平面收缩期位移(TAPSE),肺动脉加速时间(PA-AT)和右心室流出道速度时间积分(RVOT-VTI)及PAT/PET、TAPSE/mPAP降低(P<0.05);3周时,右心室内径(RVID)增加、TAPSE/PAT升高(P<0.05)。与对照组比,模型组大鼠mPAP、RVHI升高(P<0.05)。模型组大鼠肺小动脉管壁增厚,中膜平滑肌细胞增生,管腔狭窄,WA%、WT%升高(P<0.05);RV心肌细胞肥大,心肌纤维化(P<0.05)。模型组大鼠心、肺增大(P<0.05)。结论用MCT诱导的PAH雄性大鼠的右心室结构与功能均发生变化,导致肺动脉高压。Objective To observe the structural and functional changes of right ventricle in male rats with pulmonary arterial hypertension(PAH)induced by monocrotaline(MCT),and to further clarify the mechanism of PAH.Methods SD rats were randomly divided into control group and model group with twelve rats in each group.The rats in the model group received a single subcutaneous injection of MCT at a dose of 40 mg· kg~(-1).Echocardiography was performed at 0,2,3 and 4 weeks after MCT injection to evaluate right ventricule function and right ventricle-pulmonary artery(RV-PA)coupling.At 4 weeks of MCT injection,mean pulmonary artery pressure(mPAP)was measured by right heart catheterization.Organs were removed and weighed to calculate organ coefficient and right ventricular hypertrophy index(RVHI).HE staining was used to observe the pathomorphological changes of pulmonary arterioles.The percentage of lumen area to the total vessel area(WA%)and the percentage of wall thickness to the outer radius of the vessel(WT%)were calculated.HE and Masson staining were adopted to observe the degree of hypertrophy and fibrosis of RV cardiomyocytes.Results Compared with 0 week,RVFW and mPAP in the model group were increased(P<0.05). The levels of TAPSE, PA-AT, RVOT-VTI and PAT/PET,TAPSE/mPAP were decreased(P<0.05).RVID and TAPSE/PAT increased at 3 weeks(P<0.05).Compared with the control group,mPAP and RVHI were increased in the model group(P<0.05).In the model group,the wall of pulmonary arterioles was thickened,the media smooth muscle cells were proliferated and the lumen was narrowed.Besides,WA% and WT% were increased(P<0.05).Cardiomyocyte hypertrophy and myocardial fibrosis were observed in RV(P<0.05).The heart and lung of the model group were enlarged(P<0.05).Conclusion Pulmonary arterial hypertension induced by MCT is caused by the changes in right ventricle structure and function in rats with PAH.

关 键 词：野百合碱 肺动脉高压 雄性 大鼠 右心室 结构 功能 变化 

分 类 号：R965[医药卫生—药理学]