Zhongguo Zhong Yao Za Zhi. 2026 May;51(9):2588-2599. doi: 10.19540/j.cnki.cjcmm.20260123.801.
ABSTRACT
This study aims to investigate the ameliorative effect of Junren Bufei Yixin Granules( JRBF) on hypoxic pulmonary hypertension(HPH) and its regulatory mechanism on the resistin like molecule-β( RELM-β)/solute carrier family 7 member 11(SLC7A11)/glutathione peroxidase 4(GPX4) signaling pathway. Sixty male C57BL/6 mice were randomly divided into a normal group, a model group, JRBF groups with low, medium, and high doses, and a sildenafil group. Except for the normal group, all the other groups were exposed to a hypoxic chamber with 10. 0%±0. 5% oxygen concentration(eight hours per day for 28 days) and were adm inistereddrugs prior to daily hypoxia exposure. After model establishment, right heart catheterization and echocardiography reveal thatJRBF significantly reduces right v entricular systolic pressure, improves the ratio of acceleration time/ejection time in the pulmonary arteriole, and ameliorates the rightventricular structural and functional parameters in HPH mice. Histopathological analysis demonstrates that JRBF effectively alleviates pulmonary arteriolar remodeling and cardiomyocyte hypertrophy. Proteomic analysis sug gests that the ferroptosis-related pathways in the HPH model are activated. Immunofluorescence results indicate that JRBF inhibits thec o-localization of α-smooth muscle actin(α-SMA) and RELM-β in pulmonary arterioles, while promoting the co-localization of α-SMAwith S LC7A11 and GPX4. Western blot and RT-qPCR analyses confirmed that JRBF downregulated RELM-β expression and upregulatedSLC7A11 and G PX4 expression in lung tissue. JRBF intervention reduced the contents of ferrous irons( Fe~(2+)) and malondialde hyde( MDA),while increasing the content of reduced glutathione in lung tissue. Through the transmission electron microsc opyobservations, it was found that JRBF ameliorated hypoxia-induced mitochondrial morphological damage in pulmonary arterial smoo thmuscle cells. Additionally, biochemical indicators of serum demonstrate that JRBF does not cause significant dysfunction of the liverand kidney. In summary, this study suggests that JRBF may inhibit Fe~(2+) accumulation and lipid peroxidation by regulating the RELM-β/SLC7A11/GPX4 signaling axes, thereby suppressing ferroptosis in pulmonary arterial smooth muscle cells and ultimately ameliorating pulmonary vascular remodeling in HPH mice.
PMID:42392814 | DOI:10.19540/j.cnki.cjcmm.20260123.801