Aim: Lung injury is a common complication of acute pancreatitis (AP), which leads to the development of acute respiratory distress syndrome and causes high mortality. In the present study, we investigated the therapeutic effect of emodin on AP-induced lung injury and explored the molecular mechanisms involved.
Materials and Methods: Thirty male Sprague-Dawley rats were randomly divided into AP (n=24) and normal (n=6) groups. Rats in the AP group received a retrograde injection of 5% sodium taurocholate into the biliary-pancreatic duct and then randomly assigned to untreated, emodin, combined emodin and ML385, and dexamethasone (DEX) groups. Pancreatic and pulmonary injury was assessed using H&E staining. In in vitro study, rat alveolar epithelial cell line L2 cells were exposed to lipopolysaccharide and treated with emodin. Nrf2 siRNA pool was applied for the knockdown of Nrf2. The contents of the pro-inflammatory cytokines in the bronchoalveolar lavage fluid and lung were determined using enzyme-linked immunosorbent assay. The expressions of related mRNAs and proteins in the lung or L2 cells were detected using real-time polymerase chain reaction, Western blot, immunohistochemistry and immunofluorescence.
Key Findings: Emodin administration alleviated pancreatic and pulmonary injury of rats with AP. Emodin administration suppressed the production of proinflammatory cytokines, downregulated NLRP3, ASC and caspase-1 expressions and inhibited NF-κB nuclear accumulation in the lung. In addition, Emodin increased Nrf2 nuclear translocation and upregulated HO-1 expression. Moreover, the anti-inflammatory effect of emodin was blocked by Nrf2 inhibitor ML385.
Conclusion: Emodin effectively protects rats against AP-associated lung injury by inhibiting NLRP3 inflammasome activation via Nrf2/HO-1 signaling.

Keywords: emodin, acute pancreatitis, lung injury, Nrf2, NLRP3 inflammasome


中文翻译：

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大黄素通过 Nrf2/HO-1 信号通路抑制 NLPR3 炎性体激活来预防急性胰腺炎相关的肺损伤。

目的：肺损伤是急性胰腺炎（AP）的常见并发症，可导致急性呼吸窘迫综合征的发展并导致高死亡率。在本研究中，我们研究了大黄素对 AP 诱导的肺损伤的治疗作用，并探讨了所涉及的分子机制。
材料和方法：将三十只雄性 Sprague-Dawley 大鼠随机分为 AP (n=24) 和正常 (n=6) 组。AP组大鼠经胆胰管逆行注射5%牛磺胆酸钠后随机分为未处理组、大黄素组、大黄素+ML385联合组和地塞米松（DEX）组。使用 H&E 染色评估胰腺和肺损伤。在体外研究中，大鼠肺泡上皮细胞系 L2 细胞暴露于脂多糖并用大黄素处理。Nrf2 siRNA 池用于敲除 Nrf2。采用酶联免疫吸附法测定支气管肺泡灌洗液和肺中促炎细胞因子的含量。采用实时聚合酶链反应、Western blot、
主要发现：大黄素给药可减轻 AP 大鼠的胰腺和肺损伤。大黄素给药抑制促炎细胞因子的产生，下调 NLRP3、ASC 和 caspase-1 的表达，并抑制肺中 NF-κB 核积累。此外，大黄素增加 Nrf2 核转位并上调 HO-1 表达。此外，大黄素的抗炎作用被 Nrf2 抑制剂 ML385 阻断。
结论：大黄素通过 Nrf2/HO-1 信号通路抑制 NLRP3 炎性体激活，有效保护大鼠免受 AP 相关性肺损伤。

关键词：大黄素 急性胰腺炎 肺损伤 Nrf2 NLRP3 炎性体