心阳片 (XYT) 已成为通过影响巨噬细胞自噬和 M2 极化来对抗脓毒症引起的心肌功能障碍 (SMID) 的潜在干预措施。本研究旨在揭示XYT在脓毒症引起的心肌功能障碍（SIMD）中的潜在机制。采用微阵列分析探讨脓毒症相关变化，并利用生物信息学分析预测lncRNA与肿瘤坏死因子受体相关因子6的结合（TRAF6）。该工作室利用​​注射脂多糖 (LPS) 诱导的 SIMD 小鼠模型，然后进行涉及不同剂量的 XYT、地高辛（阳性对照）或 si-LncSICRNT1 的治疗。 7天后，测量了小鼠毛发/精神状态/饮食/体重的评估，并通过超声心动图进行了心脏功能。采用苏木精-伊红染色观察心肌组织变化。此外，用 oe-LncSICRNT1、si-TRAF6 及其阴性对照、XYT 或自噬抑制剂 3-甲基腺嘌呤 (3-MA)（阳性对照）处理经过 LPS 进行 M1 极化的骨髓源性巨噬细胞 (BMDM)。采用 RT-qPCR 和蛋白质印迹分析来评估 LncSICRNT1、TRAF6、Beclin-1、LC3II/LC3I 和 p62 水平。免疫组织化学和流式细胞术用于 M1/M2 极化标记，而酶联免疫吸附测定 (ELISA) 则测量炎症因子水平。使用 RNA Pull-down 和 RNA 免疫沉淀 (RIP) 测定法探测 TRAF6 和 LncSICRNT1 之间的相互作用。芯片分析获得了 1463 个差异表达的 lncRNA，包括 LINC01550 (LncSICRNT1)。进一步预测表明LncSICRNT1极有可能直接结合TRAF6。 LPS诱导的SIMD小鼠的XYT治疗导致睡眠/毛发/饮食/活动显着增强，体重/左心室舒张末期内径（LVEDd）/左心室射血分数（LVEF）/左心室缩短分数（LVFS）增加。这些改善与 LncSICRNT1 表达升高和 TRAF6 蛋白水平降低相关，最终减少心肌炎症反应并改善心功能。值得注意的是，XYT 可抑制巨噬细胞 M1 极化，同时增强 M2 极化，最终通过 LncSICRNT1 调节有益于心脏功能。此外，该研究还揭示了 LncSICRNT1 通过靶向 TRAF6 表达来调节 Beclin-1 泛素化并抑制巨噬细胞自噬。该研究强调了 XYT 通过提高 LncSICRNT1 表达、影响 TRAF6 表达和调节 Beclin-1 泛素化来改善 LPS 诱导的 SIMD 的潜力。这些作用共同抑制巨噬细胞自噬并促进 M1/M2 极化，有助于改善心脏功能。© 2023。作者。

Xinyang Tablet (XYT) has emerged as a potential intervention to counter sepsis-induced myocardial dysfunction (SMID) by influencing macrophage autophagy and M2 polarization. This study aimed to unravel the underlying mechanism of XYT in sepsis-induced myocardial dysfunction (SIMD).A microarray analysis was employed to explore sepsis-related changes, and bioinformatics analysis was used to predict lncRNAs binding to tumor necrosis factor receptor-associated factor 6 (TRAF6). This studio utilized SIMD mouse models induced by lipopolysaccharide (LPS) injection, followed by treatments involving varied doses of XYT, digoxin (positive control), or si-LncSICRNT1. After seven days, evaluations encompassing mouse hair/mental state/diet/weight were measured, and cardiac function via echocardiography were conducted. Myocardial tissue changes were observed using hematoxylin-eosin staining. Additionally, bone marrow-derived macrophages (BMDMs) subjected to LPS for M1 polarization were treated with oe-LncSICRNT1, si-TRAF6 and their negative control, XYT, or autophagy inhibitor 3-Methyladenine (3-MA) (positive control). RT-qPCR and Western blot analyses were employed to assess LncSICRNT1, TRAF6, Beclin-1, LC3II/LC3I, and p62 levels. Immunohistochemistry and flow cytometry were used for M1/M2 polarization markers, while enzyme-linked immunosorbent assay (ELISA) gauged inflammatory factor levels. Interaction between TRAF6 and LncSICRNT1 was probed using RNA pull-down and RNA immunoprecipitation (RIP) assays.Chip analysis obtained 1463 differentially expressed lncRNAs, including LINC01550 (LncSICRNT1). Further prediction indicated that LncSICRNT1 was highly likely to directly bind to TRAF6. XYT treatment in LPS-induced SIMD mice led to notable enhancements in sleep/hair/diet/activity, increased weight/left ventricular end-diastolic diameter (LVEDd)/LV ejection fraction (LVEF)/LV fraction shortening (LVFS). These improvements were associated with elevated LncSICRNT1 expression and decreased TRAF6 protein levels, culminating in reduced myocardial inflammatory responses and improved cardiac function. Notably, XYT was found to suppress macrophage M1 polarization, while enhancing M2 polarization, ultimately benefitting cardiac function via LncSICRNT1 modulation. Furthermore, the study revealed LncSICRNT1 modulated Beclin-1 ubiquitination and restrained macrophage autophagy by targeting TRAF6 expression.The study highlights XYT's potential to ameliorate LPS-induced SIMD by elevating LncSICRNT1 expression, influencing TRAF6 expression, and regulating Beclin-1 ubiquitination. These actions collectively inhibit macrophage autophagy and foster M1/M2 polarization, contributing to cardiac function improvement.© 2023. The Author(s).