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黄芪甲苷治疗缺氧性肺动脉高压的体内外实验

Astragaloside IV in Hypoxic Pulmonary Hypertension: an In Vivo and In Vitro Experiments.

作者信息

Zhang Xiaofeng, Feng Yi, Gao Xiaolong, Hao Xuan, Zhang Junru, Long Yunhong, Zhang Shumiao, Li Ling

机构信息

Department of Cardiology, Shaanxi Provincial Hospital of Chinese Medicine, No. 4 Xihuamen Street, Xian 710003, China.

Department of Nephrology, Shaanxi Provincial Hospital of Chinese Medicine, No. 4 Xihuamen Street, Xian 710003, China.

出版信息

Appl Biochem Biotechnol. 2022 Dec;194(12):6319-6334. doi: 10.1007/s12010-022-04027-y. Epub 2022 Aug 2.

Abstract

The objective of study was to find the actions of astragaloside IV (ASIV) on PAH due to monocrotaline (MCT) in rats. Intraperitoneal injection of 60 mg/ kg MCT was injected to rats, come after by ASIV treatment with doses of 10 mg/kg daily once or 30 mg/kg of dose for twenty one days once daily. RVSP, serum inflammatory cytokines, RVH, and the other pathological parameters of the pulmonary arteries were evaluated. ASIV attenuated the increased pulmonary artery pressure and its structure in rat modification due to MCT. Additionally, ASIV avoided the rise in tumor necrosis factor (TNF)-α and interleukin (IL)-1β levels in the blood serum, and their expression of gene in the pleural parts, which was caused by MCT. ASIV promoted apoptotic resistance of HPASMCs and weakened the hypoxia-induced proliferation. ASIV shows over expression of caspase-3, caspase-9, p21, p27, and Bax, while ASIV downregulated Bcl-2, phospho-ERK, HIF-1α, and protein appearance in HPASMCs. These findings of the in vitro and the in vivo experiment indicate that astragaloside IV exerts protective effects against pulmonary arterial pressure, and may have action to be improved into pharmacological drug for pulmonary arterial pressure treatment.

摘要

本研究的目的是探究黄芪甲苷(ASIV)对大鼠野百合碱(MCT)所致肺动脉高压(PAH)的作用。给大鼠腹腔注射60mg/kg MCT,随后分别用10mg/kg剂量每日一次或30mg/kg剂量每日一次进行ASIV治疗,持续21天。评估右心室收缩压(RVSP)、血清炎性细胞因子、右心室肥厚(RVH)以及肺动脉的其他病理参数。ASIV减轻了MCT所致大鼠模型中肺动脉压力及其结构的增加。此外,ASIV避免了血清中肿瘤坏死因子(TNF)-α和白细胞介素(IL)-1β水平的升高,以及MCT所致胸膜部位这些基因的表达。ASIV促进了人肺动脉平滑肌细胞(HPASMCs)的凋亡抵抗并减弱了缺氧诱导的增殖。ASIV使半胱天冬酶-3(caspase-3)、半胱天冬酶-9(caspase-9)、p21、p27和Bax过表达,而ASIV下调了HPASMCs中Bcl-2、磷酸化细胞外信号调节激酶(phospho-ERK)、缺氧诱导因子-1α(HIF-1α)和蛋白表达。这些体内和体外实验结果表明,黄芪甲苷对肺动脉压力具有保护作用,可能具有开发成为治疗肺动脉压力的药物的潜力。

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