Epidemiological and experimental animal studies indicate that there is a high risk for the incidence of neuropsychiatric disorders suffering from cardiovascular diseases such as myocardial infarction (MI). However, the potential mechanism of this association remains largely unknown. This study sought to evaluate whether epigenetic alterations in the hippocampus is associated with MI-induced anxiety-like behavior in rats. MI was induced by occlusion of the left anterior descending artery in adult female rats. Anxiety-like behavior was examined by elevated plus maze, light-dark box, and open field test. Relative gene and protein levels expression in the hippocampus were tested by qRT-PCR and western blotting, respectively. We found that MI rats exhibited anxiety-like behavior compared with those in controls, and there is a positive correlation between MI and anxiety-like behavior. We also found that MI decreased KDM6B while increased SIRT1 expression in the hippocampus of MI rats relative to those in controls. In addition, MI not only increased levels of IL-1β, bax, and cleaved-caspase 3, but also increased Iba-1 and GFAP expression in the hippocampus, as compared to those in controls, suggesting a promotion of neuro-inflammation and apoptosis in hippocampus. Co-immunoprecipitation assay illustrated that H3K27me3 functioned by counteracting with YAP activation in the hippocampus of MI rats relative to those in controls. Together, these results suggest a potential role of hippocampal epigenetic signaling in MI-induced anxiety-like behavior in rats, and pharmacological targeting KDM6B or SIRT1 could be a strategy to ameliorate anxiety-like behavior induced by MI.

流行病学和实验动物研究表明，患有心肌梗塞（MI）等心血管疾病的神经精神障碍的发病风险很高。然而，这种关联的潜在机制在很大程度上仍然未知。本研究旨在评估海马体的表观遗传改变是否与 MI 诱导的大鼠焦虑样行为有关。MI 是由成年雌性大鼠左前降支动脉闭塞引起的。焦虑样行为通过高架十字迷宫、明暗盒和野外测试进行检查。分别通过 qRT-PCR 和蛋白质印迹测试海马中的相对基因和蛋白质水平表达。我们发现与对照组相比，MI 大鼠表现出类似焦虑的行为，并且 MI 与焦虑样行为之间存在正相关。我们还发现，与对照组相比，MI 降低了 KDM6B，同时增加了 MI 大鼠海马中 SIRT1 的表达。此外，与对照组相比，MI 不仅增加了 IL-1β、bax 和 cleaved-caspase 3 的水平，而且增加了海马中 Iba-1 和 GFAP 的表达，表明促进了神经炎症和细胞凋亡在海马体中。免疫共沉淀试验表明，相对于对照组，H3K27me3 通过抵消 MI 大鼠海马中的 YAP 激活而发挥作用。总之，这些结果表明海马表观遗传信号在 MI 诱导的大鼠焦虑样行为中的潜在作用，