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建立稳定的肺动脉高压小鼠模型的新方法OA

A novel approach for developing a stable pulmonary arterial hypertension mouse model

中文摘要英文摘要

目的 利用野百合碱(monocrotaline,MCT)建立稳定的肺动脉高压(pulmonary hypertension,PH)小鼠模型.方法 选择6~8周龄的雄性C57BL/6小鼠,通过每周腹腔注射1次MCT,连续注射3周.在最后一次注射后的第10、20、30天对小鼠进行检测,利用 0.55 mm × 20 mm 一次性输液针头经肋间肌穿刺小鼠右心室,通过medlab生物信号采集系统检测小鼠的右心室收缩压(right ventricular systolic pressure,RVSP),分离心脏,称小鼠体质量(body mass,BM),右心室(right ventricular,RV),左心室加室间隔(left ventricular+septum,LV+S)的质量,计算右心室肥厚指数(right ventricular hypertrophy index,RVHI)=RV/BM以及富尔顿指数(RV/LV+S),取肺组织病理切片并作苏木素-伊红(HE)染色,肺血管内皮细胞标志性蛋白 CD31 和 α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)的免疫荧光(immunofluorescence,IF)染色,观察肺血管结构改变.结果 MCT组小鼠在3个检测时间点的RVSP、RVHI以及RV/LV+S,均显著高于对照组小鼠,HE染色也可观察到肺血管壁的明显增厚,IF染色观察到CD31的表达量降低,而α-SMA的表达量升高.结论 每周1次,连续3周腹腔注射固定剂量的MCT,可以构建周期30 d稳定的肺动脉高压小鼠模型.

Objective To develop a reliable mouse model of pulmonary hypertension(PH)using monocrotaline(MCT).Methods Female C57BL/6 mice aged 6~8 weeks were selected and administered MCT through intraperitoneal injection once weekly for three weeks.On days 10,20,and 30 after the final injection,the mice were evaluated.A 0.55 mm x 20 mm disposable infusion needle was inserted through the intercostal muscles to access the right ventricle,and the right ventricular systolic pressure(RVSP)was recorded with the medlab biological signal acquisition system.The heart was dissected,the body mass(BM),right ventricle(RV),and left ventricle plus septum(LV+S)were measured,and then the right ventricular hypertrophy index(RVHI)=RV/BM and fulton index(RV/LV+S)were calculated.Lung tissue sections were prepared for pathological analysis.Then,immunofluorescence(IF)staining was performed for hematoxylin-eosin(HE)and α-smooth muscle actin(α-SMA)to examine changes in pulmonary vascular structure.Results At each of the three time points,RVSP,RVHI,and RV/LV+S values in MCT group mice were markedly higher than those in the control group.HE staining confirmed significant thickening of the pulmonary vascular walls,while IF staining revealed the expression levels of α-SMA proteins were significantly increased whereas the expression levels of CD31 proteins were significantly decreased.Conclusions Administering a consistent dose of MCT via weekly intraperitoneal injections for three weeks can create a stable mouse model of pulmonary hypertension over 30 d.

郭思佳

福建省肺干细胞重点实验室,泉州市特级人才创新实验室,福建医科大学附属第二医院,福建泉州 362000

生物科学

肺动脉高压野百合碱小鼠模型腹腔注射肋间肌穿刺α-SMA

pulmonary hypertensionmonocrotalinemouse modelintraperitoneal injectionintercostal muscle punctureα-SMA

《中国实验动物学报》 2026 (2)

213-219,7

福建省自然科学基金项目(2024J01672),福建省卫生领域科技创新联合项目(2024Y9366).Funded by Fujian Provincial Natural Science Foundation(2024J01672),Scientific and Technological Innovation Joint Capital Projects in the Health Field of Fujian Province(2024Y9366).

10.3969/j.issn.1005-4847.2026.02.006

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