清胰颗粒作用机制探讨及临床回顾性评价：胰腺清洁剂改善伴有急性呼吸窘迫综合征的重症急性胰腺炎

BACKGROUND: Despite its extensive utilization in Chinese hospitals for treating acute pancreatitis (AP) and related acute respiratory distress syndrome (ARDS), the active components and mechanisms underlying the action of Qingyi Granule (QYKL) remain elusive. METHODS: This study consists of four parts. First, we used Mendelian randomization (MR) to investigate the causal relationship between AP, cytokine, and ARDS. Next, 321 patients were collected to evaluate the efficacy of QYKL combined with dexamethasone (DEX) in treating AP. In addition, we used UHPLC-QE-MS to determine the chemical constituents of QYKL extract and rat serum after the oral administration of QYKL. The weighted gene coexpression network analysis (WGCNA) method was used to find the main targets of AP-related ARDS using the GSE151572 dataset. At last, a AP model was established by retrograde injection of 5% sodium taurocholate. RESULTS: MR showed that AP may have a causal relationship with ARDS by mediating cytokine storms. Retrospective study results showed early administration of QYKL was associated with a lower incidence of ARDS, mortality, admissions to the intensive care unit, and length of stay in AP patients compared to the Control group. Furthermore, we identified 23 QYKL prototype components absorbed into rat serum. WGCNA and differential expression analysis identified 1558 APALI-related genes. The prototype components exhibited strong binding activity with critical targets. QYKL has a significant protective effect on pancreatic and lung injury in AP rats, and the effect is more effective after combined treatment with DEX, which may be related to the regulation of the IL-6/STAT3 signaling pathway. CONCLUSION: By integrating MR, retrospective analysis, and systematic pharmacological methodologies, this study systematically elucidated the therapeutic efficacy of QYKL in treating AP-related ARDS, establishing a solid foundation for its medicinal use.

背景：尽管清胰颗粒（QYKL）在中国医院中广泛用于治疗急性胰腺炎（AP）和相关的急性呼吸窘迫综合征（ARDS），但其作用的活性成分和机制仍不清楚。

方法：本研究包括四个部分。首先，我们使用孟德尔随机化（MR）来研究 AP、细胞因子和 ARDS 之间的因果关系。接下来，收集了 321 名患者来评估 QYKL 联合地塞米松（DEX）治疗 AP 的疗效。此外，我们使用 UHPLC-QE-MS 来确定 QYKL 提取物和大鼠血清在口服 QYKL 后的化学成分。使用 GSE151572 数据集，加权基因共表达网络分析（WGCNA）方法来寻找与 AP 相关的 ARDS 的主要靶点。最后，通过逆行注射 5%牛磺胆酸钠建立 AP 模型。

结果：MR 显示 AP 可能通过介导细胞因子风暴与 ARDS 存在因果关系。回顾性研究结果表明，与对照组相比，早期给予 QYKL 可降低 ARDS 的发生率、死亡率、入住重症监护病房的比例和 AP 患者的住院时间。此外，我们鉴定出 23 种 QYKL 原型成分被吸收到大鼠血清中。WGCNA 和差异表达分析鉴定出 1558 个与 APALI 相关的基因。原型成分与关键靶标表现出强烈的结合活性。QYKL 对 AP 大鼠的胰腺和肺损伤具有显著的保护作用，与 DEX 联合治疗的效果更为显著，这可能与调节 IL-6/STAT3 信号通路有关。

结论：通过整合 MR、回顾性分析和系统药理学方法，本研究系统阐明了 QYKL 治疗 AP 相关 ARDS 的疗效，为其药用奠定了坚实的基础。