Stress and anxiety contribute to the pathophysiology of irritable bowel syndrome (IBS), a female-predominant disorder of the gut-brain axis, characterized by abdominal pain due to heightened visceral sensitivity. In the current study, we aimed to evaluate in female rats whether epigenetic remodeling in the limbic brain, specifically in the central nucleus of the amygdala (CeA), is a contributing factor in stress-induced visceral hypersensitivity. Our results showed that 1 h exposure to water avoidance stress (WAS) for 7 consecutive days decreased histone acetylation at the GR promoter and increased histone acetylation at the CRH promoter in the CeA. Changes in histone acetylation were mediated by the histone deacetylase (HDAC) SIRT-6 and the histone acetyltransferase CBP, respectively. Administration of the HDAC inhibitor trichostatin A (TSA) into the CeA prevented stress-induced visceral hypersensitivity through blockade of SIRT-6 mediated histone acetylation at the GR promoter. In addition, HDAC inhibition within the CeA prevented stress-induced histone acetylation of the CRH promoter. Our results suggest that, in females, epigenetic modifications in the limbic brain regulating GR and CRH expression contribute to stress-induced visceral hypersensitivity and offer a potential explanation of how stress can trigger symptoms in IBS patients.

压力和焦虑会导致肠易激综合症（IBS）的病理生理学，这是一种女性为主的肠脑轴疾病，其特征是由于内脏敏感性增强而导致腹痛。在当前的研究中，我们的目的是在雌性大鼠中评估边缘脑，特别是杏仁核中央核（CeA）的表观遗传重塑是否是应激诱导的内脏超敏反应的一个促成因素。我们的结果表明，连续 7 天暴露于避水应激 (WAS) 1 小时会降低 CeA 中 GR 启动子的组蛋白乙酰化，并增加 CRH 启动子的组蛋白乙酰化。组蛋白乙酰化的变化分别由组蛋白脱乙酰酶 (HDAC) SIRT-6 和组蛋白乙酰转移酶 CBP 介导。将 HDAC 抑制剂曲古抑菌素 A (TSA) 注射到 CeA 中，可通过阻断 GR 启动子处 SIRT-6 介导的组蛋白乙酰化来预防应激诱导的内脏超敏反应。此外，CeA 内的 HDAC 抑制可防止应激诱导的 CRH 启动子组蛋白乙酰化。我们的研究结果表明，在女性中，调节 GR 和 CRH 表达的边缘大脑中的表观遗传修饰有助于应激诱导的内脏超敏反应，并为应激如何引发 IBS 患者的症状提供了潜在的解释。