Xiang Changpei, Zhang Fangbo, Gao Jinhuan, Guo Feifei, Zhang Mao, Zhou Rui, Wei Junying, Wang Ping, Zhang Yi, Zhang Jingjing, Yang Hongjun
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
Institute of Molecular Medicine, Peking University, Beijing 100871, China.
Oxid Med Cell Longev. 2021 Feb 16;2021:8049079. doi: 10.1155/2021/8049079. eCollection 2021.
Traditional Chinese medicine has shown great safety and efficacy in the treatment of heart failure (HF), whereas the mechanism remains unclear. In this study, the protective effect of Yixin-shu (YXS) capsules, a conventional medicine for various cardiovascular diseases, against myocardial ischemia-induced HF in rats was systematically investigated by RNA-seq technology. HF rats treated with YXS (0.8 or 1.6 g/kg/d, ig) for 6 weeks had significantly decreased brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) and collagen III and attenuated cardiac structure rupture and collagen deposition. Additionally, YXS treatment decreased the levels of interleukin-1 (IL-1), interleukin 6 (IL-6), tumor necrosis factor- (TNF-), and lactate dehydrogenase (LDH) and TUNEL-positive rate and the nitrotyrosine staining, but increased levels of glutathione (GSH), total antioxidant capacity (T-AOC) activity, and mitochondrial membrane potential. Further experiments demonstrated that YXS restored Trx2 and inhibited the phosphorylation of JNK and p38, thereby improving cardiac function in the rats with HF. Silencing Trx2 decreased the protection of YXS in the response to HO as evidenced by the increase of caspase-3 activity and decrease of GSH level. Thus, YXS enhanced heart function and decreased myocardial damage through restoring Trx2 and inhibiting JNK and p38 activation in ischemia-induced HF.
中药在治疗心力衰竭（HF）方面已显示出很高的安全性和有效性，但其机制尚不清楚。在本研究中，运用RNA测序技术系统研究了益心舒（YXS）胶囊（一种用于治疗多种心血管疾病的传统药物）对大鼠心肌缺血诱导的HF的保护作用。用YXS（0.8或1.6 g/kg/d，灌胃）治疗6周的HF大鼠，其脑钠肽（BNP）、心房钠尿肽（ANP）和Ⅲ型胶原显著降低，心脏结构破裂和胶原沉积减轻。此外，YXS治疗降低了白细胞介素-1（IL-1）、白细胞介素6（IL-6）、肿瘤坏死因子-（TNF-）和乳酸脱氢酶（LDH）水平以及TUNEL阳性率和硝基酪氨酸染色，但提高了谷胱甘肽（GSH）水平、总抗氧化能力（T-AOC）活性和线粒体膜电位。进一步实验表明，YXS可恢复Trx2并抑制JNK和p38的磷酸化，从而改善HF大鼠的心功能。沉默Trx2可降低YXS对HO的保护作用，这可通过caspase-3活性增加和GSH水平降低得以证明。因此，YXS通过恢复Trx2并抑制缺血诱导的HF中JNK和p38的激活来增强心功能并减少心肌损伤。
