Abstract：
BACKGROUND: Septic heart failure has been recognized as a puzzle since antiquity and poses a major challenge to modern medicine. Our previous work has demonstrated the potential effects of lycorine (LYC) on sepsis and septic myocardial injury. Nonetheless, further exploration is needed to elucidate the underlying cellular and molecular mechanisms.
METHODS: In this study, we conducted transcriptome analysis and weighted gene co-expression network analysis (WGCNA) to identify the key genes and reveal the mechanism of LYC against septic heart failure.
OBJECTIVE: This study aims to apply bioinformatic analysis and experimental validations to explore the protective effects and underlying mechanism of LYC on the cecal ligation and puncture (CLP)-induced sepsis model mice.
RESULTS: Transcriptome analysis revealed the differentially expressed genes (DEGs) following LYC treatment. WGCNA analysis identified gene modules associated with LYC-mediated protection, with BCL3 emerging as a core gene within these modules. Notably, BCL3 was an overlapping gene of DEGs and WGCNA core genes induced by LYC treatment, and is highly negatively correlated with cardiac function indicator. In vivo and in vitro study further prove that LYC exerted a protective effect against septic myocardial injury through inhibiting BCL3. BCL3 siRNA ameliorated LPS-induced cardiac injury and inflammation, while BCL3 overexpression reversed the protective effect of LYC against LPS injury.
CONCLUSIONS: In summary, our findings demonstrate the significant attenuation of septic myocardial disorder by LYC, with the identification of BCL3 as a pivotal target gene. This study is the first to report the role of BCL3 in sepsis and septic myocardial injury. Furthermore, the strategy for hub genes screening used in our study facilitates a comprehensive exploration of septic targets and reveals the potential targets for LYC effect. These findings may offer a new therapeutic strategy for the management of septic heart failure, highlighting the cardioprotective effect of LYC as adjunctive therapy for sepsis management.
METHODS: In this study, we conducted transcriptome analysis and weighted gene co-expression network analysis (WGCNA) to identify the key genes and reveal the mechanism of LYC against septic heart failure.
OBJECTIVE: This study aims to apply bioinformatic analysis and experimental validations to explore the protective effects and underlying mechanism of LYC on the cecal ligation and puncture (CLP)-induced sepsis model mice.
RESULTS: Transcriptome analysis revealed the differentially expressed genes (DEGs) following LYC treatment. WGCNA analysis identified gene modules associated with LYC-mediated protection, with BCL3 emerging as a core gene within these modules. Notably, BCL3 was an overlapping gene of DEGs and WGCNA core genes induced by LYC treatment, and is highly negatively correlated with cardiac function indicator. In vivo and in vitro study further prove that LYC exerted a protective effect against septic myocardial injury through inhibiting BCL3. BCL3 siRNA ameliorated LPS-induced cardiac injury and inflammation, while BCL3 overexpression reversed the protective effect of LYC against LPS injury.
CONCLUSIONS: In summary, our findings demonstrate the significant attenuation of septic myocardial disorder by LYC, with the identification of BCL3 as a pivotal target gene. This study is the first to report the role of BCL3 in sepsis and septic myocardial injury. Furthermore, the strategy for hub genes screening used in our study facilitates a comprehensive exploration of septic targets and reveals the potential targets for LYC effect. These findings may offer a new therapeutic strategy for the management of septic heart failure, highlighting the cardioprotective effect of LYC as adjunctive therapy for sepsis management.
摘要：
背景：化脓性心力衰竭自古以来就被认为是一个难题，对现代医学构成了重大挑战。我们以前的工作已经证明了石蒜碱（LYC）对败血症和败血症心肌损伤的潜在影响。尽管如此，需要进一步探索以阐明潜在的细胞和分子机制。
方法：在本研究中，我们进行了转录组分析和加权基因共表达网络分析(WGCNA),以鉴定关键基因并揭示LYC抗感染性心力衰竭的机制.
目的：本研究应用生物信息学分析和实验验证，探讨LYC对盲肠结扎穿孔（CLP）脓毒症模型小鼠的保护作用及其机制。
结果：转录组分析揭示了LYC处理后差异表达的基因(DEGs)。WGCNA分析确定了与LYC介导的保护相关的基因模块，BCL3成为这些模块中的核心基因。值得注意的是,BCL3是LYC处理诱导的DEGs和WGCNA核心基因的重叠基因,与心功能指标呈高度负相关。体内和体外研究进一步证明LYC通过抑制BCL3对脓毒症心肌损伤具有保护作用。BCL3siRNA改善LPS诱导的心脏损伤和炎症,而BCL3过表达逆转了LYC对LPS损伤的保护作用。
结论：总之，我们的研究结果表明，LYC可显着减轻败血症的心肌紊乱，与鉴定BCL3为关键靶基因。本研究首次报道BCL3在脓毒症和脓毒症心肌损伤中的作用。此外，我们研究中使用的枢纽基因筛选策略有助于全面探索脓毒症靶标,并揭示LYC效应的潜在靶标.这些发现可能为感染性心力衰竭的管理提供了新的治疗策略。强调LYC作为脓毒症管理的辅助治疗的心脏保护作用。
方法：在本研究中，我们进行了转录组分析和加权基因共表达网络分析(WGCNA),以鉴定关键基因并揭示LYC抗感染性心力衰竭的机制.
目的：本研究应用生物信息学分析和实验验证，探讨LYC对盲肠结扎穿孔（CLP）脓毒症模型小鼠的保护作用及其机制。
结果：转录组分析揭示了LYC处理后差异表达的基因(DEGs)。WGCNA分析确定了与LYC介导的保护相关的基因模块，BCL3成为这些模块中的核心基因。值得注意的是,BCL3是LYC处理诱导的DEGs和WGCNA核心基因的重叠基因,与心功能指标呈高度负相关。体内和体外研究进一步证明LYC通过抑制BCL3对脓毒症心肌损伤具有保护作用。BCL3siRNA改善LPS诱导的心脏损伤和炎症,而BCL3过表达逆转了LYC对LPS损伤的保护作用。
结论：总之，我们的研究结果表明，LYC可显着减轻败血症的心肌紊乱，与鉴定BCL3为关键靶基因。本研究首次报道BCL3在脓毒症和脓毒症心肌损伤中的作用。此外，我们研究中使用的枢纽基因筛选策略有助于全面探索脓毒症靶标,并揭示LYC效应的潜在靶标.这些发现可能为感染性心力衰竭的管理提供了新的治疗策略。强调LYC作为脓毒症管理的辅助治疗的心脏保护作用。
