Effect of fenofibrate on right ventricular hypertrophy in rats with high-altitude heart disease and its mechanisms
10.3969/j.issn.1000-4718.2025.06.012
- VernacularTitle:非诺贝特对高原性心脏病大鼠右心室肥大的影响及其机制
- Author:
Xiaoying ZHANG
1
;
Qi SI
;
Jiajia WU
;
Shadi LI
Author Information
1. 西藏民族大学医学院,西藏民族大学藏药检测技术教育部工程研究中心,西藏藏医药研究中心藏药活性成分及药理机制研究联合实验室,陕西 咸阳 712082
- Publication Type:Journal Article
- Keywords:
fenofibrate;
high-altitude heart disease;
right ventricular hypertrophy;
glucolipid metabolism
- From:
Chinese Journal of Pathophysiology
2025;41(6):1153-1161
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To investigate the effect of fenofibrate(FF)on the heart of rats with high-altitude heart dis-ease-induced right ventricular hypertrophy(H-RVH),and to explore the mechanisms and associated signaling pathways.METHODS:A total of 36 six-week-old male SD rats were randomly divided into control,model(H-RVH),and FF inter-vention(H-RVH+FF)groups with 12 rats each.A rat model of H-RVH was established by single subcutaneous injection of Sugen 5416(20 mg/kg)and exposure to a hypoxic condition(5 000 m above sea level)for 21 d in all groups except the control group.The rats in H-RVH+FF group were given FF(60 mg·kg-1·d-1)through gavage,while those in control and model groups received equal volume of saline once daily for 21 d.Rat heart gross morphology was observed,and the heart volume and weight,right ventricular weight and other hypertrophy indexes were measured in each group at the end of the experiment.A right heart floating catheter was used for measuring pulmonary artery and right ventricular pressure.Cardi-ac function was checked through cardiac ultrasonography.The serum levels of atrial natriuretic peptide(ANP),N-termi-nal pro-brain natriuretic peptide(NT-proBNP),free fatty acids(FFA),and myocardial tissue glucose(Glu)in all groups of rats were detected.The protein expression of peroxisome proliferator-activated receptor α(PPARα),fatty acid binding protein 1(FABP1),carnitine palmitoyl transferase 1a(CPT1a),pyruvate dehydrogenase kinase(PDK),and pyruvate dehydrogenase(PDH)were detected through Western blot.RESULTS:(1)Compared with the control group,the H-RVH group showed a significant increase in heart morphology and weight and increases in heart weight/body weight(HW/BW),heart volume,right ventricular weight/heart weight(RVW/HW),and Fulton index(FI)(P<0.05).Cardiac mor-phology,volume,heart weight,and HW/BW significantly decreased in the fenofibrate intervention group compared with the H-RVH group(P<0.05).RVW/HW and FI also decreased.(2)The right heart float catheter test showed that the mean right ventricular pressure(mRVP)and mean pulmonary artery pressure(mPAP)significantly increased in the H-RVH group compared with the control group(P<0.01).The increases in mRVP and mPAP were reversed in rats in the fe-nofibrate intervention group compared with the H-RVH group.(3)Cardiac ultrasonography showed that compared with the control group,the H-RVH group had significantly increased right ventricular anterior wall(RVAW)and right ventricular posterior wall(RVPW)thickness(P<0.01),significantly decreased right ventricular end-diastolic diameter(RVEDD),and right ventricular end-diastolic length(RVEDL)(P<0.01).In addition,pulmonary artery acceleration time(PAAT)was reduced,ejection time(PAET)was prolonged,and PAAT/PAET ratio decreased(P<0.01).Compared with the H-RVH group,the fenofibrate intervention group showed significant decreases in RVAW and RVPW(P<0.05),increases in RVEDD and RVEDL,and an increase in PAAT/PAET ratio.(4)The kit assay showed that the levels of ANP and NT-Pro BNP in serum were significantly higher in the H-RVH group than in the control group(P<0.05),while the levels of both were lower in the fenofibrate intervention group.The levels of serum FFA and myocardial tissue Glu levels(P<0.05)were significantly higher in the H-RVH group than in the control group.The levels of serum FFA and myocardial tissue Glu level were significantly lower in the fenofibrate intervention group than in the H-RVH group(P<0.05).(5)Western blot results showed that the expression levels of PPARα,FABP1,CPT1a,and PDH in the myocardial tissues of rats in the H-RVH group were significantly reduced(P<0.01),whereas the expression level of PDK significantly increased relative to those of the control group(P<0.01).All the effects on the above indices in the H-RVH group can be significantly re-versed by fenofibrate intervention(P<0.05).CONCLUSION:Fenofibrate exerts a protective effect on the hearts of rats with right ventricular hypertrophy associated with high-altitude heart disease by activating PPARα/FABP1/CPT1a,en-hancing fatty acid oxidation,inhibiting PDK,and activating PDH to promote the aerobic oxidation of glucose.Hence,the medication can ameliorate glucose-lipid metabolism disorders.
