Feixin Decoction Ameliorates Hypoxic Pulmonary Hypertension by Mediating Mitochondrial Damage via RELM-β/DRP1 Signaling Pathway
Objective Investigating the protective effects and potential mechanisms of Feixin Decoction in rats with hypoxic pulmonary hypertension(HPH).Methods Fifty male SD rats were randomly allocated into the control,model,Feixin Decoction groups(12.75 mg·kg-1、25.5 mg·kg-1、51 mg·kg-1)as well as the sildenafil positive control group(25mg·kg-1),each group consisting of 10 rats.They were exposed to a hypoxic chamber for 8 hours daily after oral administration for 3 weeks.The right ventricular systolic pressure(RVSP)was assessed via right heart catheterization in all groups.Tricuspid annular systolic displacement(TAPSE),right ventricular anterior wall thickness(RVAWT),right ventricular hypertrophy index(RVHI),pulmonary arterial acceleration time(PAAT),and pulmonary arterial ejection time(PET)were evaluated using a small-animal cardiac ultrasound system.HE staining was used to evalu-ate the remodeling of rat pulmonary arteries,while transmission electron microscopy was employed to observe the submicroscopic structure of mitochondria in rat pulmonary arteries.Adenosine triphosphate(ATP)kit is available to detect ATP level in rat lung tissue;reactive oxygen species(ROS)kit is used to detect ROS level in lung tissue;RT-PCR was used to detect the mRNA levels of resistin oxygen molecule β(RELM-β),dynamin-related protein 1(DRP1),and mitochondrial fission protein 1(FIS1)in rat lung tissues;immu-nohistochemistry was performed to determine the expression levels of RELM-β in rat pulmonary arteries;and immunofluorescence was used to measure the expression levels of DRP1 and FIS1 in rat pulmonary arteries.Results The model group exhibited a notable rise in RVSP and RVAWT,along with a decrease in TAPSE and PAAT compared to the control group.Significant alterations were observed in the pulmonary vasculature,mitochondrial microstructure damage(P＜0.01),elevated ROS levels(P＜0.01),reduced ATP production(P＜0.01),and notably increased levels of RELM-β,DRP1,and FIS1 mRNA and proteins(P＜0.01).Compared to the model group,RVSP and RVAWT were significantly reduced,TAPSE and PAAT were significantly increased in the medium and high dose groups of Feixin Decoction(P＜0.01).Additionally,pulmonary artery remodeling and mitochondrial damage showed significant im-provement(P＜0.01).Levels of ROS were reduced(P＜0.01),ATP production increased(P＜0.01),and there was a significant down-regulation of RELM-β,DRP1,and FIS1 mRNA and protein levels(P＜0.01).Conclusion Feixin Decoction may improve mi-tochondrial damage,decrease ROS levels,regulate ATP production,and ease pulmonary vascular remodeling and right heart function in HPH rats by blocking the RELM-β/DRP1 pathway.
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