Department of Hepato-Biliary-Pancreatic Surgery, Henan Provincial People's Hospital (People's Hospital of Zhengzhou University), Zhengzhou, Henan 450000, China.
Biomed Res Int. 2018 Nov 28;2018:1294951. doi: 10.1155/2018/1294951. eCollection 2018.
The rapid production and release of a large number of inflammatory cytokines can cause excessive local and systemic inflammation in severe acute pancreatitis (SAP) and multiple organ dysfunction syndrome (MODS), especially pancreatitis-associated acute lung injury (P-ALI), which is the main cause of early death in patients with SAP. The NLRP3 inflammasome plays an important role in the maturation of IL-1 and the inflammatory cascade. Here, we established a model of SAP using wild-type (NLRP3) and NLRP3 knockout (NLRP3) mice by intraperitoneal injections of caerulein (Cae) and lipopolysaccharide (LPS). Pathological injury to the pancreas and lungs, the inflammatory response, and neutrophil infiltration were significantly mitigated in NLRP3 mice. Furthermore, INF-39, an NLRP3 inflammasome inhibitor, could reduce the severity of SAP and P-ALI in a dose-dependent manner. Our results suggested that SAP and P-ALI were alleviated by NLRP3 deficiency in mice, and thus, reducing NLRP3 expression may mitigate SAP-associated inflammation and P-ALI.
大量炎症细胞因子的迅速产生和释放可导致重症急性胰腺炎（SAP）和多器官功能障碍综合征（MODS）发生过度的局部和全身炎症，特别是胰腺炎相关的急性肺损伤（P-ALI），这是 SAP 患者早期死亡的主要原因。NLRP3 炎性小体在 IL-1 的成熟和炎症级联反应中起重要作用。在这里，我们通过腹腔内注射 CAE 和脂多糖（LPS）建立了野生型（NLRP3）和 NLRP3 敲除（NLRP3）小鼠的 SAP 模型。NLRP3 小鼠的胰腺和肺部的病理损伤、炎症反应和中性粒细胞浸润明显减轻。此外，NLRP3 炎性小体抑制剂 INF-39 可呈剂量依赖性降低 SAP 和 P-ALI 的严重程度。我们的研究结果表明，NLRP3 缺失可减轻 SAP 和 P-ALI 小鼠的 SAP 和 P-ALI，因此，降低 NLRP3 表达可能减轻 SAP 相关炎症和 P-ALI。
