Chen Qi, Zhang Dini, Bi Yunhui, Zhang Weiwei, Zhang Yuhan, Meng Qinghai, Li Yu, Bian Huimin
School of Pharmacy, Nanjing University of Chinese Medicine, Xianlin Avenue, Qixia District, Nanjing, 210023 Jiangsu China.
Key Laboratory on Biosafety, Nanjing Institute of Environmental Sciences, Ministry of Ecology and Environment, Nanjing, 210042 China.
Chin Med. 2020 Jun 15;15:63. doi: 10.1186/s13020-020-00345-7. eCollection 2020.
Heart failure (HF) is one of the most common causes of cardiovascular diseases in the world. Currently, the drugs used to treat HF in the clinic may cause serious side effects. Liguzinediol, 2, 5-dimethyl-3, 6-dimethyl-pyrazine, is a compound synthesized after the structural modification of ligustrazine (one active ingredient of ). We aimed to observe the effects of liguzinediol on preventing HF and explore the related mechanisms.
The ligation of left anterior descending coronary artery was operated to established the myocardial infarction (MI) model in Sprague-Dawley rats. Cardiac functions were recorded by echocardiography and hemodynamics. The changes in the Renin-Angiotensin-Aldosterone System (RAAS), inflammation, and oxidative stress were detected by radioimmunoassay and Elisa kits. Western blot and real-time PCR were applied to determine the expressions of the TGF-β1/Smads pathway.
Firstly, liguzinediol enhanced the systolic and diastolic functions of the heart in MI rats. Liguzinediol improved ventricular remodeling by reducing myocardial cell necrosis, as well as reducing collagen deposition and myocardial fibrosis. Then, liguzinediol suppressed the activation of RAAS, inhibited the synthesis of pro-inflammation factors, and reduced oxidative stress. In the end, liguzinediol also down-regulated the expressions of the TGF-β1/Smads pathway.
Liguzinediol could alleviate HF caused by MI in rats, and the protective effect was associated with the regulation of the TGF-β1/Smads pathway.
心力衰竭（HF）是全球心血管疾病最常见的病因之一。目前，临床上用于治疗HF的药物可能会引起严重的副作用。川芎嗪二醇，即2,5-二甲基-3,6-二乙基吡嗪，是对川芎嗪（一种有效成分）进行结构修饰后合成的化合物。我们旨在观察川芎嗪二醇对预防HF的作用并探索其相关机制。
通过结扎左冠状动脉前降支建立Sprague-Dawley大鼠心肌梗死（MI）模型。采用超声心动图和血流动力学记录心脏功能。通过放射免疫分析和酶联免疫吸附测定试剂盒检测肾素-血管紧张素-醛固酮系统（RAAS）、炎症和氧化应激的变化。应用蛋白质免疫印迹法和实时荧光定量PCR法测定TGF-β1/Smads信号通路的表达。
首先，川芎嗪二醇增强了MI大鼠心脏的收缩和舒张功能。川芎嗪二醇通过减少心肌细胞坏死、减少胶原蛋白沉积和心肌纤维化改善心室重构。其次，川芎嗪二醇抑制RAAS的激活，抑制促炎因子的合成，并降低氧化应激。最后，川芎嗪二醇还下调了TGF-β1/Smads信号通路的表达。
川芎嗪二醇可减轻大鼠MI所致的HF，其保护作用与调节TGF-β1/Smads信号通路有关。
