Inhibition effect of perillyl alcohol on pulmonary vascular remodeling in hypoxia-induced pulmonary hypertension rats and its mechanism
10.3867/j.issn.1000-3002.2025.08444
- VernacularTitle:紫苏醇对低氧性肺动脉高压大鼠肺血管重构的抑制作用及机制
- Author:
Yiwen WANG
1
;
Haijun BAI
;
Zhanqiang LI
;
Dianxiang LU
;
Xingmei NAN
;
Zhanting YANG
Author Information
1. 青海大学医学院公共卫生系,青海 西宁 810001
- Publication Type:Journal Article
- Keywords:
hypoxia-induced pulmonary hypertension;
perillyl alcohol;
pulmonary vascular remodeling;
pulmonary vascular fibrosis;
ACE2-Ang(1-7)-Mas axes;
ACE-AngⅡ-AT1R axes
- From:
Chinese Journal of Pharmacology and Toxicology
2025;39(8):569-580
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the impact of perilla alcohol on pulmonary vascular remod-eling in hypoxia-induced pulmonary hypertension(HPH)rats and to assess its regulatory effects on the angiotensin-converting enzyme 2(ACE2)-angiotensin(1-7)[Ang(1-7)]-mas proto-oncogene receptor(Mas)and ACE-angiotensinⅡ(AngⅡ)-angiotensin type 1 receptor(AT1R)axes.METHODS An HPH rat model was established by keeping them in a hypobaric chamber that simulated an altitude of 5 000 m for 28 d.Male SD rats were randomly divided into the control group,hypoxia group,hypoxia+sildenafil group(ig administration of 30 mg·kg-1),and hypoxia+perillyl alcohol groups(ig administration of 25,50 and 100 mg·kg-1 respectively).After 28 d,the levels of glutamic-oxaloacetic transaminase(GOT),glutamic-pyruvic transaminase(GPT),and blood urea nitrogen(BUN)in rat serum were measured to evaluate the toxic effects of perillyl alcohol on rat organs.Mean pulmonary artery pressure(mPAP)was measured via right ventricular catheterization.HE staining was used to observe the patho morphological changes of pulmonary vessels in HPH rats and measure the percentages of the vascularwall area[WA(%)],wall thickness[WT(%)],lumen area[LA(%)].The right ventricular hypertrophy level and α-smooth muscle actin(α-SMA)expression level were detected by immunohistochemistry and immunofluorescence.Western blotting was used to detect the protein expression levels of α-SMA,ACE,AT1R,AngⅡ,ACE2 and Mas in lung tissues of rats.Enzyme-linked immunosorbent assay(ELISA)was employed to mea-sure the content of Ang(1-7)in lung tissues.RESULTS Compared with the control group,the serum levels of GOT,GPT and BUN in the hypoxia group rats were significantly increased,but were signifi-cantly decreased by perillyl alcohol and sildenafil intervention.Compared with the control group,mPAP,WA(%),WT(%),right ventricular inner diameter(RVID),right ventricular free wall thickness(RVFWT)and fibrosis levels were significantly increased in the hypoxia group,while LA(%)was signifi-cantly decreased.Besides,the protein expression levels of α-SMA,ACE,AT1R and AngⅡ in lung tissues were significantly elevated while those of ACE2 and Mas,as well as Ang(1-7)content were signifi-cantly decreased in hypoxia group compared to the control group.Following intervention with perillyl alcohol and sildenafil,the protein expression levels of ACE and AngⅡin lung tissues of HPH rats were significantly decreased compared to the model group while those of ACE2 and Mas receptor,along with the content of Ang(1-7),were significantly increased.Perillyl alcohol significantly reduced the protein expression level of AT1R while sildenafil had no significant effect.CONCLUSION Perillyl alcohol can lower mPAP levels by improving pulmonary vascular remodeling and reducing pulmonary vascular fibrosis in HPH rats.The mechanism may be related to the regulatory effects on the ACE-AngⅡ-AT1R and ACE2-Ang(1-7)-Mas axes.
