利舒康胶囊调节HIF-1α/NF-κB信号通路对大鼠低氧性肺动脉高压的影响
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篇名: 利舒康胶囊调节HIF-1α/NF-κB信号通路对大鼠低氧性肺动脉高压的影响
TITLE: Effects of Lishukang capsules on hypoxic pulmonary artery hypertension in rats by modulating the HIF-1α/NF-κB signaling pathway
摘要: 目的 探究利舒康胶囊调节低氧诱导因子1α(HIF-1α)/核因子κB(NF-κB)信号通路对大鼠低氧性肺动脉高压(HPAH)的影响。方法60只大鼠随机分为对照组、模型组、阳性对照组(西地那非30mg/kg)和利舒康低、中、高剂量组(利舒康胶囊6、12、18g/kg),每组10只。除对照组外,其余各组大鼠采用间歇性低氧法(模拟5000m海拔)建立HPAH模型;建模同时每日灌胃相应药物或生理盐水,连续28d。末次给药24h内,检测大鼠平均肺动脉压(MPAP)和右心室肥厚指数(RVHI),观察肺组织病理情况,检测肺组织中α平滑肌肌动蛋白(α-SMA)表达和HIF-1α、NF-κBmRNA表达,以及HIF-1α、NF-κBp65蛋白表达情况。结果与模型组比较,利舒康中、高剂量组和阳性对照组大鼠的MPAP、RVHI均显著降低(P<0.05);肺组织中α-SMA表达和HIF-1α、NF-κBmRNA表达,以及HIF-1α和NF-κBp65蛋白表达均显著下调(P<0.05);肺血管重塑均不同程度改善。结论利舒康胶囊对大鼠HPAH具有改善作用,其机制可能与抑制HIF-1α/NF-κB信号通路有关。
ABSTRACT: OBJECTIVE To explore the effects of Lishukang capsules on hypoxic pulmonary artery hypertension (HPAH) rats by regulating the HIF-1α/NF-κB signaling pathway. METHODS Sixty rats were randomly divided into control group, model group, positive control group (sildenafil, 30 mg/kg), Lishukang low-, medium- and high-dose groups (Lishukang capsules 6, 12, 18 g/kg), with 10 rats in each group. Except for control group, the HPAH model was induced by intermittent hypoxia method (simulating an altitude of 5 000 m) in other groups; at the same time, they were given relevant medicine or normal saline intragastrically, for consecutive 28 days. Within 24 hours of the last administration, the mean pulmonary artery pressure (MPAP) and right ventricule hypertrophy index (RVHI) of rats were detected; pathological morphology of lung tissue was observed, and the expression of α-smooth muscle actin (α-SMA), mRNA expressions of HIF-1α and NF-κB as well as protein expressions of HIF-1α and NF-κB p65 in lung tissue were determined. RESULTS Compared with model group, MPAP and RVHI in Lishukang medium- and high-dose groups and positive control group were all decreased significantly (P<0.05); the expression of α-SMA, mRNA expressions of HIF-1α and NF-κB, and protein expressions of HIF-1α and NF-κB p65 in lung tissue were all decreased significantly (P<0.05); additionally, pulmonary vascular remodeling was improved to varying degrees. CONCLUSIONS Lishukang capsules may protect HPAH rats, the mechanism of which may be associated with inhibiting the HIF-1α/NF- κB signaling pathway.
期刊: 2025年第36卷第16期
作者: 李龙昱;徐富菊;王欣;张松达
AUTHORS: LI Longyu,XU Fuju,WANG Xin,ZHANG Songda
关键字: 利舒康胶囊;低氧性肺动脉高压;肺血管重塑;低氧诱导因子1α;核因子κB
KEYWORDS: Lishukang capsules; hypoxic pulmonary artery hypertension; pulmonary vascular remodeling; HIF-1α; NF-κB
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