Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
Sci Rep. 2016 Dec 23;6:39809. doi: 10.1038/srep39809.
Vascular remodeling is an important complication of hypertension with oxidative stress-related profibrotic pathways involved. The transforming growth factor β1 (TGF-β1) has been shown to be a potential target of vasoprotection, and has multiple roles in vascular remodeling. Acetyl-11-Keto-β-Boswellic Acid (AKBA) is one of the active principles of Boswellic acids, and shows antioxidant activity in many diseases. The study is to determine effects of AKBA on systemic oxidative stress of hypertension and vascular remodeling. In the experiments, spontaneously hypertensive rats (SHR) were used. And in vitro, fibroblast was pretreated with AKBA before Ang II stimuli. In the results, treatment of AKBA markedly reduced oxidative stress, and decreased vascular remodeling by restoring vascular wall parameters and improving vascular reactivity. AKBA dramatically reduced TGF-β1 and Smad3 expression, as shown in immunofluorescence and immunohistochemistry. In cultured fibroblast, AKBA decreased intracellular ROS levels. Cell viability and proliferation, as well as migration were inhibited by AKBA. Additionally, treatment of AKBA significantly decreased TGF-β1 secretion in culture supernatant. Expression of TGF-β1, Smad3, P-Smad3 and Smad7 were also decreased by AKBA in fibroblast. In conclusion, AKBA is able to attenuate oxidative stress and profibrotic mechanisms, and improve vascular remodeling in hypertension through TGF-β1/Smad3 pathway.
血管重构是高血压的一个重要并发症，涉及氧化应激相关的致纤维化途径。转化生长因子β1（TGF-β1）已被证明是血管保护的一个潜在靶点，在血管重构中具有多种作用。乙酰-11-酮-β-乳香酸（AKBA）是乳香酸的活性成分之一，在许多疾病中具有抗氧化活性。本研究旨在确定 AKBA 对高血压系统性氧化应激和血管重构的影响。在实验中，使用自发性高血压大鼠（SHR）。体外，用 AKBA 预处理成纤维细胞，然后用 Ang II 刺激。结果表明，AKBA 治疗显著降低氧化应激，通过恢复血管壁参数和改善血管反应性来减少血管重构。免疫荧光和免疫组化显示，AKBA 显著降低 TGF-β1 和 Smad3 的表达。在培养的成纤维细胞中，AKBA 降低了细胞内 ROS 水平。AKBA 抑制细胞活力、增殖和迁移。此外，AKBA 处理显著减少了培养上清液中 TGF-β1 的分泌。AKBA 还降低了成纤维细胞中 TGF-β1、Smad3、P-Smad3 和 Smad7 的表达。综上所述，AKBA 能够通过 TGF-β1/Smad3 途径减轻氧化应激和致纤维化机制，改善高血压中的血管重构。
