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含桃红四物汤血清通过调节VHL/HIF-1/VEGF信号通路增强大鼠主动脉内皮细胞的血管生成。

Taohong Siwu-Containing Serum Enhances Angiogenesis in Rat Aortic Endothelial Cells by Regulating the VHL/HIF-1/VEGF Signaling Pathway.

作者信息

Tang Zhi, Li Wangyang, Xie Hongzan, Jiang Shengping, Pu Yunqing, Xiong Hui

机构信息

Department of Orthopedics, Xiangtan Chinese Medicine Hospital, Xiangtan 411100, China.

Department of Clinical Medicine, Hunan University of Traditional Chinese Medicine, Changsha 410208, China.

出版信息

Evid Based Complement Alternat Med. 2021 Nov 22;2021:6610116. doi: 10.1155/2021/6610116. eCollection 2021.

Abstract

BACKGROUND

The incidence of bone fracture and bone-related diseases is increasing every year. Angiogenesis plays a vital role in fracture healing and bone repair. This study assessed the benefits of Taohong Siwu (TSW) decoction on angiogenesis in isolated rat aortic endothelial cells (RAEC) treated with TSW-containing serum.

METHODS

The components of TSW decoction were analyzed by liquid chromatography-mass spectrometry (LC-MS). TSW-containing serum was prepared by gavage of TSW decoction to Sprague-Dawley (SD) rats. The effects of TSW-containing serum on the viability, migration, wound healing, and angiogenesis of RAEC were detected by the MTT, transwell, wound healing, and Matrigel lumen formation assays, respectively. In addition, the effects of an HIF-1 inhibitor on TSW-containing serum-induced RAEC were also assessed. The effects of TSW-containing serum on the expression of the HIF-1 signaling pathway were evaluated by qRT-PCR and western blot analysis.

RESULTS

LC-MS revealed that TSW decoction primarily contained isomaltulose, choline, D-gluconic acid, L-pipecolic acid, hypotaurine, albiflorin, and tryptophan. TSW-containing serum significantly increased the viability, migration, wound healing, and angiogenesis of RAEC in a dose-dependent manner. Furthermore, our results demonstrated that HIF-1 and VEGF expressions were increased in the cells of TSW-containing serum groups, whereas VHL expression was decreased. The effects of TSW-containing serum were reversed by treatment with an HIF-1 inhibitor.

CONCLUSION

These results suggested that TSW decoction enhanced angiogenesis by regulating the VHL/HIF-1/VEGF signaling pathway.

摘要

背景

骨折及骨相关疾病的发病率逐年上升。血管生成在骨折愈合和骨修复中起着至关重要的作用。本研究评估了桃红四物汤(TSW)水煎剂对含TSW血清处理的离体大鼠主动脉内皮细胞(RAEC)血管生成的益处。

方法

采用液相色谱 - 质谱联用(LC - MS)分析TSW水煎剂的成分。通过给Sprague - Dawley(SD)大鼠灌胃TSW水煎剂制备含TSW血清。分别采用MTT法、Transwell法、伤口愈合实验和基质胶管腔形成实验检测含TSW血清对RAEC活力、迁移、伤口愈合及血管生成的影响。此外,还评估了HIF - 1抑制剂对含TSW血清诱导的RAEC的影响。通过qRT - PCR和蛋白质免疫印迹分析评估含TSW血清对HIF - 1信号通路表达的影响。

结果

LC - MS显示TSW水煎剂主要含有异麦芽糖、胆碱、D - 葡萄糖酸、L - 哌啶酸、亚牛磺酸、白花芍药苷和色氨酸。含TSW血清以剂量依赖方式显著提高RAEC的活力、迁移、伤口愈合及血管生成能力。此外,我们的结果表明,含TSW血清组细胞中HIF - 1和VEGF表达增加,而VHL表达降低。用HIF - 1抑制剂处理可逆转含TSW血清的作用。

结论

这些结果表明,TSW水煎剂通过调节VHL/HIF - 1/VEGF信号通路增强血管生成。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c48/8629617/b388c075de17/ECAM2021-6610116.002.jpg

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