Ma Chengxu, Zhao Xinke, Chang Juan, Guo Huan, Wei Huiping, Fu Zhaoyuan, Li Yingdong
College of Integrated Traditional Chinese and Western Medicine, Gansu University of Chinese Medicine, Lanzhou 730000, China.
Affiliated Hospital of Gansu University of Chinese Medicine, Lanzhou 730000, China.
Evid Based Complement Alternat Med. 2020 Apr 21;2020:4675851. doi: 10.1155/2020/4675851. eCollection 2020.
Radiation-induced myocardial fibrosis (RIMF) is the main pathological change associated with radiation-induced heart toxicity after radiation therapy in patients with thoracic tumors. There is an antifibrosis effect of Radix Angelica Sinensis and Radix Hedysari (RAS-RH) ultrafiltration extract from Danggui Buxue decoction (DBD) in X-irradiation-induced rat myocardial fibrosis, and this study aimed to investigate whether that effect correlated with apoptosis and oxidative stress damage in primary rat cardiac fibroblasts; further, the potential mechanisms were also explored. In this study, we first found that the RAS-RH antifibrosis effect was associated with the upregulation of microRNA-200a and the downregulation of TGF-1/smad3 and COL1. In addition, we also found that the antifibrosis effect of RAS-RH was related to the induction of apoptosis in primary rat cardiac fibroblasts and to the prevention of damage caused by reactive oxygen species (ROS). Interestingly, primary rat cardiac fibroblasts exposed to X-ray radiation underwent apoptosis less frequently in the absence of RAS-RH. Therefore, RAS-RH has the ability to protect against fibrosis, which could be occurring through the induction of apoptosis and the resistance to oxidative stress in rats with X-irradiation-induced myocardial fibrosis; thus, in a model of RIMF, RAS-RH acts against X-irradiation-induced cardiac toxicity.
放射性心肌纤维化(RIMF)是胸部肿瘤患者放疗后放射性心脏毒性相关的主要病理变化。当归补血汤(DBD)的当归-红芪超滤提取物(RAS-RH)对X射线诱导的大鼠心肌纤维化具有抗纤维化作用,本研究旨在探讨该作用是否与原代大鼠心脏成纤维细胞的凋亡及氧化应激损伤相关;此外,还探索了其潜在机制。在本研究中,我们首先发现RAS-RH的抗纤维化作用与microRNA-200a的上调以及TGF-1/smad3和COL1的下调有关。此外,我们还发现RAS-RH的抗纤维化作用与原代大鼠心脏成纤维细胞凋亡的诱导以及活性氧(ROS)所致损伤的预防有关。有趣的是,在无RAS-RH的情况下,暴露于X射线辐射的原代大鼠心脏成纤维细胞凋亡频率较低。因此,RAS-RH具有抗纤维化的能力,这可能是通过诱导X射线诱导的心肌纤维化大鼠的凋亡以及抵抗氧化应激来实现的;因此,在RIMF模型中,RAS-RH可对抗X射线诱导的心脏毒性。