中国药理学通报2024，Vol.40Issue(1)：62-69,8.DOI:10.12360/CPB202307069
薄荷醇对低压低氧诱导小鼠肺动脉高压的作用及机制研究
Effect of menthol on hypobaric hypoxia-induced pulmonary arterial hypertension in mice and its mechanism
摘要
Abstract
Aim To study the effect of menthol on hy-pobaric hypoxia-induced pulmonary arterial hyperten-sion and explore the underlying mechanism in mice.Methods 10 to 12 weeks old wild type(WT)mice and TRPM8 gene knockout(TRPM8-/-)mice were randomly divided into control group,menthol group,hypobaric hypoxia group and hypobaric hypoxia plus menthol group.The pulmonary acceleration time(PAT)and pulmonary ejection time(PET)were ob-served by echocardiography,the right ventricular sys-tolic blood pressure(RVSP)were measured by right heart catheterization,and right ventricular hypertrophy index(RVHI)was calculated.In addition,the re-modeling of pulmonary arterioles(＜100 μm)was ob-served using HE staining,the expressions of Krüppel-like factor 4(KLF4)and proliferating cell nuclear an-tigen(PCNA)were detected by Western blot.Moreo-ver,the proliferation and migration of pulmonary artery smooth muscle cells(PASMCs)treated with hypoxia(3％O2)or hypoxia plus menthol(100 μmol·L-1)were measured.Results PAT and PAT/PET ratio in-creased(P＜0.05),while RVSP and RVHI de-creased(P＜0.05)in menthol treated wild-type mice.At the same time,the wild type mice showed re-duced pulmonary artery thickening and lumen stenosis(P＜0.05),increased KLF4 expression(P＜0.05),and decreased PCNA expression(P＜0.05).Menthol treatment did not affect PAT,PAT/PET,RVSP,RVHI,pulmonary vascular remodeling,KLF4 and PC-NA expression in TRPM8-/-mice(P＞0.05).Men-thol inhibited the proliferation and migration of PASMCs(P＜0.01,P＜0.05).Conclusion Men-thol ameliorates hypobaric hypoxia-induced pulmonary vascular remodeling and pulmonary arterial hyperten-sion by activating TRPM8 in mice.关键词
薄荷醇/瞬时受体电位通道M8/Krüppel样因子4/低压低氧性肺动脉高压/肺血管重构/肺动脉平滑肌细胞Key words
menthol/transient receptor potential melastatin 8(TRPM8)/Kruppel-like factor 4/hypo-baric hypoxia-induced pulmonary arterial hypertension/pulmonary vascular remodeling/pulmonary artery smooth muscle cells(PASMCs)分类
医药卫生引用本文复制引用
王武帅,胡陶,杨耀,何滢蓉,杨曦,段清华,杜萱,王强..薄荷醇对低压低氧诱导小鼠肺动脉高压的作用及机制研究[J].中国药理学通报,2024,40(1):62-69,8.基金项目
四川省自然科学基金资助项目(No 2022NSFSC0820) （No 2022NSFSC0820）
西部战区总医院院管课题(No 2021-XZYG-B28) （No 2021-XZYG-B28）
