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基于蛋白质组学分析的刺五加苷防治低氧性肺动脉高压机制的研究。

Study on the mechanism of echinacoside in preventing and treating hypoxic pulmonary hypertension based on proteomic analyses.

机构信息

Department of Pharmacy, Qinghai Minzu University, Xining, China.

Qinghai Provincial Key Laboratory of Tibetan Medicine Pharmacology and Safety Evaluation, Northwest Institute of Plateau Biology, Chinese Academy of Science, Xining, China.

出版信息

Pharmacol Res Perspect. 2024 Oct;12(5):e70025. doi: 10.1002/prp2.70025.

Abstract

Hypoxic pulmonary hypertension (HPH), a chronic condition affecting the cardiopulmonary system, has high mortality. Echinacoside (ECH) is a phenylethanoid glycoside, which is used to ameliorate pulmonary vascular remodeling and pulmonary vasoconstriction in rats. Accordingly, we aimed to explore the mechanism of ECH in preventing and treating HPH. Sprague Dawley rats were housed in a hypobaric hypoxia chamber for 28 days to obtain the HPH model. The experimental rats were randomly allocated into the following several groups: normoxia group, chronic hypoxia group, and ECH group. The therapeutic results of ECH (10, 20, and 40 mg/kg) showed that ECH reduced mPAP, Hb, Hct, and RVHI in HPH rats. Then this work employed label-free quantitative proteomic analysis, western blotting, and RT-PCR to investigate the mechanism by which ECH prevents HPH. The results found that in the chronic hypoxia group, the levels of ACSL1, COL6A1, COL4A2, COL1A1, and PC increased compared to the normoxia group. However, the opposite effect was observed in the chronic hypoxia group treated with ECH. The study indicates that the administration of ECH may slow the pathological progression of HPH by suppressing the inflammatory response, inhibiting smooth muscle cell proliferation, and minimizing the deposition of extracellular matrix.

摘要

低氧性肺动脉高压(HPH)是一种影响心肺系统的慢性疾病,死亡率很高。松果菊苷(ECH)是一种苯乙醇苷,用于改善大鼠的肺血管重构和肺血管收缩。因此,我们旨在探讨 ECH 预防和治疗 HPH 的机制。将 Sprague Dawley 大鼠饲养在低气压缺氧室中 28 天,以获得 HPH 模型。将实验大鼠随机分为以下几组:常氧组、慢性缺氧组和 ECH 组。ECH(10、20 和 40mg/kg)的治疗结果表明,ECH 降低了 HPH 大鼠的 mPAP、Hb、Hct 和 RVHI。然后,这项工作采用无标记定量蛋白质组学分析、western blot 和 RT-PCR 来研究 ECH 预防 HPH 的机制。结果发现,在慢性缺氧组中,与常氧组相比,ACSL1、COL6A1、COL4A2、COL1A1 和 PC 的水平升高。然而,在慢性缺氧组用 ECH 治疗时,观察到相反的效果。该研究表明,ECH 的给药可能通过抑制炎症反应、抑制平滑肌细胞增殖和最小化细胞外基质的沉积来减缓 HPH 的病理进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5ef/11472809/d7f2c67a90cf/PRP2-12-e70025-g004.jpg

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