Dong Zhiwu, Yang Lin, Jiao Jianlin, Jiang Yongliang, Li Hao, Yin Gaosheng, Yang Ping, Sun Lin
Faculty of Basic Medical Science, Kunming Medical University, Kunming, Yunnan, China.
Department of Cardiology, The Second Affiliated Hospital, Kunming Medical University, Kunming, China.
Front Pharmacol. 2022 Sep 27;13:995102. doi: 10.3389/fphar.2022.995102. eCollection 2022.
Myocardial ischemia/reperfusion (I/R) injury after percutaneous coronary intervention (PCI) is common in acute myocardial infarction. Aspirin is commonly prescribed as anti-thrombotic therapy with coronary heart disease (CHD). However, long-term use of aspirin causes severe gastric mucosal damage. Gastrodin is a Chinese natural medicine with anti-inflammatory and anti-oxidative properties. In this study, we investigated the effects of combined therapy with aspirin and gastrodin on the myocardial and gastric mucosal injury in response to myocardial I/R injury and underlying mechanisms using the Sprague-Dawley (SD) rat model. Our results demonstrated that myocardial I/R caused significant cardiac dysfunction and gastric mucosal damage. Administration of aspirin led to significantly reduce myocardial infarction size and myocardial enzyme release, as well as significantly improved cardiac function through exerting anti-inflammatory effects. However, aspirin exacerbated gastric mucosal damage by increasing the levels of inflammatory mediators and endothelin (ET) while reducing prostaglandin E2 (PGE2) levels. The combined treatment with aspirin and gastrodin not only significantly protected gastric mucosa by normalizing the expression levels of the inflammatory factors, ET and PGE2, but also significantly reduced myocardial infarction size and improved cardiac function by inhibiting inflammation in response to I/R. The combination therapy also dramatically down-regulated the levels of pyroptosis-related proteins in the myocardium and gastric mucosa. The combination therapy showed obviously reduced level of thromboxane B2 (TXB2), which was simultaneously accompanied with increased levels of the tissue plasminogen activator (t-PA). This suggested that gastrodin did not inhibit the anti-thrombotic function of aspirin. Accordingly, aspirin in combination with gasrtodin protected the structural and functional integrity of the heart and stomach by suppressing pyroptosis and inflammation. Therefore, combination of aspirin and gastrodin is a promising treatment for cardiac dysfunction and gastric mucosa injury after myocardial I/R.
经皮冠状动脉介入治疗（PCI）后发生的心肌缺血/再灌注（I/R）损伤在急性心肌梗死中很常见。阿司匹林是冠心病（CHD）抗血栓治疗的常用药物。然而，长期使用阿司匹林会导致严重的胃黏膜损伤。天麻素是一种具有抗炎和抗氧化特性的中国天然药物。在本研究中，我们使用Sprague-Dawley（SD）大鼠模型，研究了阿司匹林与天麻素联合治疗对心肌I/R损伤所致心肌和胃黏膜损伤的影响及其潜在机制。我们的结果表明，心肌I/R导致显著的心功能障碍和胃黏膜损伤。给予阿司匹林可显著减小心肌梗死面积并减少心肌酶释放，还通过发挥抗炎作用显著改善心功能。然而，阿司匹林通过增加炎症介质和内皮素（ET）水平、降低前列腺素E2（PGE2）水平而加重胃黏膜损伤。阿司匹林与天麻素联合治疗不仅通过使炎症因子、ET和PGE2的表达水平正常化而显著保护胃黏膜，还通过抑制I/R反应中的炎症显著减小心肌梗死面积并改善心功能。联合治疗还显著下调心肌和胃黏膜中焦亡相关蛋白的水平。联合治疗显示血栓素B2（TXB2）水平明显降低，同时组织型纤溶酶原激活剂（t-PA）水平升高。这表明天麻素并未抑制阿司匹林的抗血栓功能。因此，阿司匹林与天麻素联合通过抑制焦亡和炎症保护心脏和胃的结构及功能完整性。所以，阿司匹林与天麻素联合是治疗心肌I/R后心功能障碍和胃黏膜损伤的一种有前景的疗法。
