Department of Cardiovascular Medicine, Baoji High-Tech Hospital, Baoji City, China.
Department of The First Outpatients, The 940th Hospital of Joint Logistics Support force of Chinese People's Liberation Army, Lanzhou City, China.
Growth Factors. 2022 Nov;40(5-6):186-199. doi: 10.1080/08977194.2022.2109469. Epub 2022 Aug 19.
This study was to probe the role of penehyclidine hydrochloride (PHC) mediating the impact of toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-kappa B (NF-κB) signalling pathway on myocardial ischaemia-reperfusion injury (MI/RI) in rats through miR-199a-3p. The rat MI/RI model was established through ligating left anterior descending (LAD) coronary artery. PHC was injected preoperatively into the model rats, and injected with miR-199a-3p lentiviral vector or TLR4 antagonist (TAK-242). Next, cardiac function of rats was examined by echocardiography, and rat serum indicators, oxidative stress levels and inflammatory factors were detected. HE staining was applied to detect pathological tissue structure, TUNEL staining to detect apoptosis rate, qRCR and western blot to detect miR-199a-3p and TLR4/MyD88/NF-κB expressions in rat myocardial tissues. Dual luciferase reporter experiment was conducted to confirm the relationship between miR-199a-3p and TLR4. In conclusion, PHC suppresses TLR4/MyD88/NF-κB signalling pathway through miR-199a-3p, thereby improving MI/RI in rats.
本研究旨在通过 miR-199a-3p 探讨盐酸戊乙奎醚(PHC)在介导 Toll 样受体 4(TLR4)/髓样分化因子 88(MyD88)/核因子-κB(NF-κB)信号通路对大鼠心肌缺血再灌注损伤(MI/RI)的影响中的作用。通过结扎左前降支(LAD)冠状动脉建立大鼠 MI/RI 模型。模型大鼠术前注射 PHC,并注射 miR-199a-3p 慢病毒载体或 TLR4 拮抗剂(TAK-242)。然后,通过超声心动图检查大鼠心功能,检测大鼠血清指标、氧化应激水平和炎症因子。采用 HE 染色检测组织病理学结构,TUNEL 染色检测细胞凋亡率,qRCR 和 Western blot 检测大鼠心肌组织中 miR-199a-3p 和 TLR4/MyD88/NF-κB 的表达。双荧光素酶报告实验验证 miR-199a-3p 与 TLR4 的关系。结论:PHC 通过 miR-199a-3p 抑制 TLR4/MyD88/NF-κB 信号通路,从而改善大鼠的 MI/RI。