Effect of naringenin on right ventricular remodeling induced by hypoxic pulmonary hypertension

doi:10.11958/20242178

Abstract

Abstract:

Objective To investigate the effect of naringenin (NAR) on right ventricular remodeling induced by hypoxic pulmonary hypertension (HPH) and its related mechanism. Methods SD rats were randomly divided into the control group (NC), the NC+NAR group,the HPH group and the HPH+NAR group, with 15 rats in each group. HPH model was established in a low-pressure hypoxic artificial chamber. After the successful construction of the model, rats in the NC+NAR group and the HPH+NAR group were given NAR 100 mg/ (kg·d) gavage once a day for 4 weeks, while rats in the NC group and the HPH group were given the same volume of normal saline once a day for 4 weeks. Right ventricular free wall thickness (RVEDWT) and end-diastolic right ventricular diameter (RVEDD) were measured by echocardiography. Right ventricular systolic pressure (RVSP) and mean pulmonary artery pressure (mPAP) were measured by cardiac catheter. Right ventricular mass ratio (RV/BW) and right ventricular hypertrophy index (RVHI) were calculated. Masson and Sirius staining of right ventricle was used to calculate the collagen volume fraction (CVF). TUNEL staining was used to evaluate the apoptosis of right ventricular cardiomyocytes. The contents of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) in right ventricular myocardium were detected. The expression of Rho associated kinase (ROCK) protein was detected by Western blot assay. Results Compared with the NC group and the NC+NAR group, mPAP, RVSP, RVEDWT, RV/BW, RVHI, right ventricular CVF, right ventricular myocardial cell apoptosis rate, MDA content and ROCK1 and ROCK2 protein expression in right ventricular myocardial tissue were increased in the HPH group. RVEDD and SOD activity in right ventricular myocardium were decreased (P<0.05). Compared with the HPH group, mPAP, RVSP, RVEDWT, RV/BW, RVHI, right ventricular CVF, right ventricular myocardial cell apoptosis rate, MDA content, ROCK1 and ROCK2 protein expression in right ventricular myocardial tissue were decreased in the HPH+NAR group, and RVEDD and SOD activity in right ventricular myocardium were increased (P<0.05). Conclusion NAR can reduce HPH-induced right ventricular remodeling, and its mechanism may be related to inhibiting ROCK signaling pathway and further improving apoptosis and oxidative stress in right ventricular myocardium.

Key words: hypoxia, hypertension, pulmonary, rho-associated kinases, apoptosis, oxidative stress, Naringenin, myocardial fibrosis

CLC Number:

R544，R541.3

Figures/Tables 9

References 23

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组别	RVEDD	RVEDWT
NC组	2.63±0.11	0.38±0.06
NC+NAR组	2.57±0.18	0.37±0.08
HPH组	1.34±0.14^ab	0.93±0.08^ab
HPH+NAR组	2.02±0.19^c	0.66±0.09^c
F	251.400^＊＊	173.800^＊＊

组别	RVEDD	RVEDWT
NC组	2.63±0.11	0.38±0.06
NC+NAR组	2.57±0.18	0.37±0.08
HPH组	1.34±0.14^ab	0.93±0.08^ab
HPH+NAR组	2.02±0.19^c	0.66±0.09^c
F	251.400^＊＊	173.800^＊＊

组别	mPAP	RVSP
NC组	19.33±2.52	24.84±2.60
NC+NAR组	21.01±2.65	25.83±4.19
HPH组	41.03±4.02^ab	48.21±2.67^ab
HPH+NAR组	30.67±3.51^c	34.60±2.99^c
F	143.800^＊＊	180.800^＊＊

组别	mPAP	RVSP
NC组	19.33±2.52	24.84±2.60
NC+NAR组	21.01±2.65	25.83±4.19
HPH组	41.03±4.02^ab	48.21±2.67^ab
HPH+NAR组	30.67±3.51^c	34.60±2.99^c
F	143.800^＊＊	180.800^＊＊

组别	RVHI	RV/BW/（g/kg）
NC组	0.31±0.01	0.70±0.03
NC+NAR组	0.30±0.02	0.68±0.04
HPH组	0.41±0.02^ab	0.94±0.05^ab
HPH+NAR组	0.37±0.02^c	0.81±0.02^c
F	124.200^＊＊	158.800^＊＊