Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, China.
Department of Cardiology, Huangpu Branch of the Ninth People's Hospital Affiliated to the Medical College of Shanghai Jiaotong University, China.
Biomed Pharmacother. 2020 Jul;127:110121. doi: 10.1016/j.biopha.2020.110121. Epub 2020 May 11.
Nicorandil exerts a protective effect against coronary microvascular dysfunction in acute myocardial infarction (AMI) patients. However, the mechanism and effect of nicorandil in hyperhomocysteinemia (HHcy) AMI patients remain unclear.
C57/BL6 mice with mild to moderate HHcy and human coronary artery endothelial cells (HCAECs) cotreated with HHcy (1 mmol/L) for 24 h and hypoxia for 6 h were selected as models. Small animal ultrasound detection was used to compare cardiac function. CD31 immunofluorescence staining and tomato lectin staining were used to assess the number of microcirculation changes in vivo. MTT, tube formation and western blotting assays were used to evaluate the effect of nicorandil on HCAECs and the PI3K/Akt/eNOS pathway.
The results showed that nicorandil improved cell viability and p-PI3K/PI3K, p-Akt/Akt, and p-eNOS/eNOS expression in the vitro HHcy and hypoxia models. The beneficial effects of nicorandil on HCAECs could be inhibited by the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 and the nitric oxide synthase (NOS) inhibitor L-NAME. In vivo, nicorandil improved the left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) in the post-HHcy + MI model, and the levels of CD31 and tomato lectin expression were higher in the nicorandil treatment group. The effectiveness of nicorandil was inhibited in the PI3K and L-NAME groups.
The results suggest that nicorandil improves Hcy-induced coronary microvascular dysfunction through the PI3K/Akt/eNOS signalling pathway.
硝酸异山梨酯对急性心肌梗死（AMI）患者的冠状动脉微血管功能障碍具有保护作用。然而，硝酸异山梨酯在高同型半胱氨酸血症（HHcy）AMI 患者中的作用机制尚不清楚。
选择轻度至中度 HHcy 的 C57/BL6 小鼠和用 HHcy（1mmol/L）孵育 24 小时和缺氧孵育 6 小时的人冠状动脉内皮细胞（HCAEC）作为模型。采用小动物超声检测比较心功能。采用 CD31 免疫荧光染色和番茄凝集素染色评估体内微循环变化的数量。采用 MTT、管形成和 Western blot 测定评估硝酸异山梨酯对 HCAEC 和 PI3K/Akt/eNOS 通路的作用。
结果表明，硝酸异山梨酯在体外 HHcy 和缺氧模型中提高了细胞活力和 p-PI3K/PI3K、p-Akt/Akt 和 p-eNOS/eNOS 的表达。PI3K 抑制剂 LY294002 和一氧化氮合酶（NOS）抑制剂 L-NAME 可抑制硝酸异山梨酯对 HCAEC 的有益作用。在体内，硝酸异山梨酯改善了 post-HHcy + MI 模型中的左心室射血分数（LVEF）和左心室缩短分数（LVFS），并且在硝酸异山梨酯治疗组中 CD31 和番茄凝集素的表达水平更高。在 PI3K 和 L-NAME 组中，硝酸异山梨酯的有效性受到抑制。
结果表明，硝酸异山梨酯通过 PI3K/Akt/eNOS 信号通路改善了 Hcy 诱导的冠状动脉微血管功能障碍。
