Abstract
OBJECTIVE: To investigate the protective effects of Buyang Huanwu decoction (BYHW) on myocardial injury induced by chronic intermittent hypoxia (CIH) in rats and to analyze its potential regulatory mechanism through the NF-κB/LOX signaling pathway. METHODS: Then, 36 adult male Sprague-Dawley (SD) rats (weighing 200-250 g) were randomly divided into six groups (n = 6): normal control (NC), CIH model, BYHW, BYHW + lipopolysaccharide (LPS), BYHW + pyrrolidinedithiocarbamate (PDTC), and LPS. Except for the NC group, all groups underwent 5 weeks of intermittent hypoxia (8 h/day) alongside their respective drug treatments. Postintervention, systolic blood pressure and heart rate were recorded. Cardiac function was evaluated by echocardiography to measure left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), and left ventricular internal dimension at end-diastole (LVDd) and left ventricular internal dimension at end-systole (LVDs). Myocardial sections were analyzed by HE and Sirius Red staining for quantitative assessment of inflammatory cell infiltration and collagen volume fraction (CVF). The protein and mRNA expression levels of NF-κB, LOX, Collagen I, and Collagen III in cardiac tissue were analyzed by Western blot and qPCR. RESULTS: Compared with the NC group, rats exposed to CIH or LPS showed elevated blood pressure and an increased heart rate, along with impaired cardiac function, as evidenced by reduced LVEF (p < 0.05) and LVFS (p < 0.05), along with increased LVDd (p < 0.05) and LVDs (p < 0.05). BYHW treatment significantly ameliorated the CIH-induced cardiac dysfunction and ventricular dilation (p < 0.05), and these improvements were further enhanced by cotreatment with BYHW and the NF-κB inhibitor PDTC (p < 0.05). Conversely, cotreatment with BYHW and the NF-κB agonist LPS attenuated the cardioprotective effects of BYHW (p < 0.05). Histologically, BYHW significantly reduced CIH-induced myocardial structural disruption, inflammatory cell infiltration, and fibrosis (CVF) (p < 0.05), effects that were potentiated by cotreatment with BYHW and PDTC, and counteracted by cotreatment with BYHW and LPS. At the molecular level, Western blot and qPCR analyses revealed that BYHW significantly reduced both the protein and mRNA levels of NF-κB, LOX, Collagen I, and Collagen III (p < 0.05) compared with the NC group. This suppression was further enhanced by cotreatment with BYHW and PDTC and attenuated by cotreatment with BYHW and LPS. CONCLUSION: BYHW improves cardiac function and reduces myocardial inflammation and fibrosis in SD rats with CIH. This effect may be related to the inhibition of the NF-κB/LOX signaling pathway. Cotreatment with BYHW and PDTC enhances this therapeutic effect, while cotreatment with BYHW and LPS attenuates this effect. This study provides preliminary experimental evidence for the cardioprotective effects of BYHW.