Li Zhe, Zhang Sha, Cao Liang, Li Wei, Ye Yu-Chen, Shi Zi-Xuan, Wang Zong-Ren, Sun Lian-Xu, Wang Jia-Wei, Jia Lin-Tao, Wang Wen
Department of Traditional Chinese Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
Second Clinical Medical College, Shaanxi University of Traditional Chinese Medicine, Xianyang, Shaanxi 710026, P.R. China.
Exp Ther Med. 2018 Feb;15(2):1847-1854. doi: 10.3892/etm.2017.5636. Epub 2017 Dec 15.
Tanshinone IIA (Tan IIA) and Astragaloside IV (AGS-IV) were used as therapeutic treatments for coronary heart diseases (CHDs) in ancient China. However, the underlying mechanisms mediating the effects of Tan IIA and AGS-IV in angiogenesis remain unknown. In the present study, mesenchymal stem cells (MSCs) were induced to differentiate into endothelial cell (EC)-like cells and the effects of Tan IIA and/or AGS-IV on the functions of these cells, including cell proliferation and tube formation, were assessed. Compared with the single-agent groups (Tan IIA or AGS-IV only), combined-agent (Tan IIA and AGS-IV) treatment significantly enhanced the proliferation and tube formation capacity of EC-like cells. In addition, the expression of connexin 37 (37), 40 and 43 in the combined-agent group was significantly increased compared with the single-agent groups. Furthermore, enhanced gap junctional intercellular communication (GJIC) was identified in the combined-agent group, as evidenced by increased dye transfer in scrape-loading dye transfer assays. In conclusion, Tan IIA and AGS-IV may promote the angiogenesis of EC-like cells by upregulating the expression of 37, 40 and 43 and enhancing GJIC function. The results of the present study may provide experimental evidence for the clinical application of Tan IIA and AGS-IV as a treatment for CHDs.
丹参酮IIA（Tan IIA）和黄芪甲苷（AGS-IV）在中国古代被用作治疗冠心病（CHD）的药物。然而，Tan IIA和AGS-IV在血管生成中的潜在作用机制尚不清楚。在本研究中，诱导间充质干细胞（MSC）分化为内皮细胞（EC）样细胞，并评估Tan IIA和/或AGS-IV对这些细胞功能的影响，包括细胞增殖和管腔形成。与单药组（仅Tan IIA或AGS-IV）相比，联合用药组（Tan IIA和AGS-IV）显著增强了EC样细胞的增殖和管腔形成能力。此外，联合用药组中连接蛋白37（Cx37）、40和43的表达与单药组相比显著增加。此外，联合用药组中细胞间缝隙连接通讯（GJIC）增强，刮擦加载染料转移试验中染料转移增加证明了这一点。总之，Tan IIA和AGS-IV可能通过上调Cx37、40和43的表达并增强GJIC功能来促进EC样细胞的血管生成。本研究结果可能为Tan IIA和AGS-IV作为CHD治疗药物的临床应用提供实验依据。
