Salvianolic acid A attenuates vascular remodeling in a pulmonary arterial hypertension rat model
Salvianolic acid A attenuates vascular remodeling in a pulmonary arterial hypertension rat model
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DOI：
10.1038/aps.2016.22
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发表时间：
2016-06-01
影响因子：
8.2
通讯作者：
Du, Guan-hua
中科院分区：
文献类型：
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作者：
Chen, Yu-cai;Yuan, Tian-yi;Du, Guan-hua
目的：目前的治疗方法对以肺动脉高压(PAH)为特征的失调性肺血管重构的治疗效果有限。本研究观察中药丹参中提取的丹酚酸A(SAA)对PAH模型大鼠血管重塑的抑制作用，并探讨其可能的作用机制。分别给予SAA(0.3、1、3 mg·kg~(-1)·d~(-1))和阳性对照波生坦(30 mg·kg~(-1)·d~(-1))灌胃4周。于第28天进行超声心动图和血流动力学检测。取心、肺，计算脏器指数和肺动脉壁厚度，进行生化和组织化学分析。结果：SAA或波生坦能有效改善MCT所致的肺血管重塑、肺血流动力学异常及随后的右室收缩压(RVSP)升高。此外，治疗还能显著减轻MCT所致的心肌肥厚损伤、肺实质损伤和胶原沉积。此外，这些治疗还减轻了MCT诱导的肺部细胞凋亡和纤维化。治疗可部分恢复MCT诱导的肺组织骨形态发生蛋白II受体(BMPRII)和磷酸化Smad1/5表达的减少。结论：SAA可改善MCT诱导的PAH大鼠肺动脉重构，其机制可能与激活BMPRII-Smad通路和抑制细胞凋亡有关。因此，SAA可能对PAH高危患者具有治疗潜力。
Aim: The current therapeutic approaches have a limited effect on the dysregulated pulmonary vascular remodeling, which is characteristic of pulmonary arterial hypertension (PAH). In this study we examined whether salvianolic acid A (SAA) extracted from the traditional Chinese medicine 'Dan Shen" attenuated vascular remodeling in a PAH rat model, and elucidated the underlying mechanisms.Methods: PAH was induced in rats by injecting a single dose of monocrotaline (MCT 60 mg/kg, sc). The rats were orally treated with either SAA (0.3, 1, 3 mg.kg(-1).d(-1)) or a positive control bosentan (30 mg.kg(-1).d(-1)) for 4 weeks. Echocardiography and hemodynamic measurements were performed on d 28. Then the hearts and lungs were harvested, the organ indices and pulmonary artery wall thickness were calculated, and biochemical and histochemical analysis were conducted. The levels of apoptotic and signaling proteins in the lungs were measured using immunoblotting.Results: Treatment with SAA or bosentan effectively ameliorated MCT-induced pulmonary artery remodeling, pulmonary hemodynamic abnormalities and the subsequent increases of right ventricular systolic pressure (RVSP). Furthermore, the treatments significantly attenuated MCT-induced hypertrophic damage of myocardium, parenchymal injury and collagen deposition in the lungs. Moreover, the treatments attenuated MCT-induced apoptosis and fibrosis in the lungs. The treatments partially restored MCT-induced reductions of bone morphogenetic protein type II receptor (BMPRII) and phosphorylated Smad1/5 in the lungs.Conclusion: SAA ameliorates the pulmonary arterial remodeling in MCT-induced PAH rats most likely via activating the BMPRII-Smad pathway and inhibiting apoptosis. Thus, SAA may have therapeutic potential for the patients at high risk of PAH.