Effects of nicorandil on inflammatory response, oxidative stress and myocardial fibrosis after myocardial infarction.

INTRODUCTION: Numerous studies have established the potential of nicorandil in alleviating myocardial fibrosis subsequent to myocardial infarction. Nevertheless, the precise mechanism underlying this effect remains incompletely elucidated. This study aims to investigate whether nicorandil can mitigate myocardial inflammation and oxidative stress during post-infarction remodeling in mice through animal experiments, thereby shedding light on its mechanism for ameliorating myocardial fibrosis after myocardial infarction by inhibiting inflammation and oxidative stress. METHODS: The male C57BL/6J mice were randomly allocated into the following groups: Sham group, MI group, Nic group and Nic + Glib group. The left anterior descending coronary artery (LAD) was ligated to induce myocardial infarction. The intervention lasted for 4 weeks after modeling in each group. Cardiac function was evaluated by echocardiography and cardiac mass index. Serum hs-CRP was quantified using ELISA. The oxidative stress level of myocardial tissue was determined using an oxidative stress detection box. HE staining and Masson staining were employed to evaluate the inflammatory response and fibrosis in myocardial tissue. Immunohistochemical staining was utilized to detect the inflammatory response and fibrosis markers in local myocardial tissue: IL-1β,TNF-α,IL-6,α-SMA and CollagenⅠ. RESULTS: Nicorandil can improve left ventricular fractional shortening (LVFS%), left ventricular ejection fraction (LVEF%), and heart mass index after myocardial infarction, and reduce serum hs-CRP and the expression of IL-1β, TNF-α, IL-6, α-SMA, and collagenⅠ in myocardial tissue. In addition, it can increase SOD and GSH-Px levels and reduce MDA content in myocardial tissue. In addition, HE and Masson staining showed that nicorandil could inhibit myocardial and perivascular fibrosis to a certain extent, and reduce the level of local inflammatory response. These beneficial effects of nicorandil were inhibited to some extent by glibenclamide. CONCLUSION: Nicorandil attenuates myocardial inflammation, oxidative stress and myocardial fibrosis levels by activating ATP-sensitive potassium channels (K-ATP), thereby improving post-MI cardiac remodeling and preserving cardiac function.