Kong Fei, Zhao Meng
Department of Endocrinology, The Fourth Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin, Heilongjiang, China.
Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang 150040, China.
Evid Based Complement Alternat Med. 2022 Apr 30;2022:9128210. doi: 10.1155/2022/9128210. eCollection 2022.
Myocardial ischemia/reperfusion (MI/R) injury is a common clinical problem after myocardial infarction without effective therapy. Loureirin B (LrB) is a kind of flavonoid with anti-inflammatory and antifibrotic activities. However, the effect of LrB on MI/R and its underlying mechanism remains elusive. In the present study, a mouse model of MI/R was established by coronary artery occlusion. Administration of LrB (0.5 mg/kg or 1 mg/kg) for 4 weeks effectively improved left ventricular (LV) function and reduced myocardial infarction in MI/R mice. MI/R-induced expression of IL-6, TNF-, and IL-1 in the hearts was reduced by LrB treatment. Histological analysis showed that LrB attenuated myocardial collagen deposition. LrB downregulated fibronectin, collagen I, collagen III, and -SMA expression. Notably, LrB inhibited the expression of profibrotic plasminogen activator inhibitor-1 (PAI-1), transforming growth factor (TGF)-1, TGF-1R, and p-Smad2/3. Consistently, LrB inhibited the activation of TGF-1/Smad signaling pathway and the expression of fibrosis-related proteins in angiotensin (Ang) II-treated cardiac fibroblasts (CFs). Overexpression of PAI-1 abolished the effects of LrB on Ang II-treated CFs, suggesting that LrB may function through regulating PAI-1. These results indicated that LrB may alleviate MI/R-induced myocardial fibrosis by inhibiting PAI-1/TGF-1/Smad signaling pathway. Thus, LrB may be a potential drug in the treatment of MI/R injury.
心肌缺血/再灌注（MI/R）损伤是心肌梗死后常见的临床问题，目前尚无有效的治疗方法。龙血素B（LrB）是一种具有抗炎和抗纤维化活性的黄酮类化合物。然而，LrB对MI/R的影响及其潜在机制仍不清楚。在本研究中，通过冠状动脉闭塞建立了MI/R小鼠模型。给予LrB（0.5mg/kg或1mg/kg）4周可有效改善MI/R小鼠的左心室（LV）功能并减少心肌梗死面积。LrB治疗可降低MI/R诱导的心脏中白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）和白细胞介素-1（IL-1）的表达。组织学分析表明，LrB可减轻心肌胶原沉积。LrB下调纤连蛋白、I型胶原、III型胶原和α-平滑肌肌动蛋白（α-SMA）的表达。值得注意的是，LrB抑制促纤维化的纤溶酶原激活物抑制剂-1（PAI-1）、转化生长因子（TGF）-β1、TGF-β1受体和磷酸化Smad2/3的表达。一致地，LrB抑制血管紧张素（Ang）II处理的心脏成纤维细胞（CFs）中TGF-β1/Smad信号通路的激活以及纤维化相关蛋白的表达。PAI-1的过表达消除了LrB对Ang II处理的CFs的作用，表明LrB可能通过调节PAI-1发挥作用。这些结果表明，LrB可能通过抑制PAI-1/TGF-β1/Smad信号通路减轻MI/R诱导的心肌纤维化。因此，LrB可能是治疗MI/R损伤的潜在药物。
