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Background <p>Severe Acute Pancreatitis (SAP) is associated with significant intestinal injury and inflammation. Hypoxia-Inducible Factor-1α (HIF-1α) and NLRP3 inflammasome have been implicated in this process, but their specific roles remain unclear.</p> Objective <p>This study aims to elucidate the roles of HIF-1α and NLRP3 in the pathogenesis of SAP and their effects on intestinal injury, barrier function, and inflammatory responses.</p> Methods <p>A SAP rat model was established, and histological changes were assessed via HE staining. Western blot was used to analyze HIF-1α and NLRP3 expression in intestinal mucosa. The effects of HIF-1α modulation were examined using the activator DMOG and inhibitor BAY87-2243. Immunohistochemistry, ELISA, and TUNEL staining were used to evaluate intestinal barrier function, permeability markers, and apoptosis.</p> Results <p>HIF-1α and NLRP3 expression significantly increased in SAP rats, peaking at 72 h. HIF-1α activation aggravated intestinal injury and barrier dysfunction, decreasing tight junction protein levels and increasing epithelial apoptosis. Enhanced intestinal permeability and elevated pro-inflammatory cytokines were also observed. Furthermore, HIF-1α activation promoted NLRP3 inflammasome assembly, resulting in increased caspase-1 and IL-1β expression.</p> Conclusion <p>HIF-1α exacerbates intestinal injury and inflammation in SAP, likely through NLRP3 inflammasome activation. Targeting HIF-1α may offer a potential therapeutic approach for SAP-induced damage and inflammation.</p>

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HIF-1α Enhances Intestinal Injury and Inflammation in Severe Acute Pancreatitis Through NLRP3 Inflammasome Activation

  • 期刊论文

  • 发表日期：

    2025年2月25日

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  • Tao Gao,
  • Huaisheng Zhang,
  • Yuan Xu,
  • Guosong He,
  • Huicong Ma,
  • Chuanming Zheng,
  • Lei Li,
  • Feng Cheng,
  • Hehe Dou,
  • Fulong Zhang,
  • Heng Zhao,
  • Zhaolei Qiu

摘要

Background

Severe Acute Pancreatitis (SAP) is associated with significant intestinal injury and inflammation. Hypoxia-Inducible Factor-1α (HIF-1α) and NLRP3 inflammasome have been implicated in this process, but their specific roles remain unclear.

Objective

This study aims to elucidate the roles of HIF-1α and NLRP3 in the pathogenesis of SAP and their effects on intestinal injury, barrier function, and inflammatory responses.

Methods

A SAP rat model was established, and histological changes were assessed via HE staining. Western blot was used to analyze HIF-1α and NLRP3 expression in intestinal mucosa. The effects of HIF-1α modulation were examined using the activator DMOG and inhibitor BAY87-2243. Immunohistochemistry, ELISA, and TUNEL staining were used to evaluate intestinal barrier function, permeability markers, and apoptosis.

Results

HIF-1α and NLRP3 expression significantly increased in SAP rats, peaking at 72 h. HIF-1α activation aggravated intestinal injury and barrier dysfunction, decreasing tight junction protein levels and increasing epithelial apoptosis. Enhanced intestinal permeability and elevated pro-inflammatory cytokines were also observed. Furthermore, HIF-1α activation promoted NLRP3 inflammasome assembly, resulting in increased caspase-1 and IL-1β expression.

Conclusion

HIF-1α exacerbates intestinal injury and inflammation in SAP, likely through NLRP3 inflammasome activation. Targeting HIF-1α may offer a potential therapeutic approach for SAP-induced damage and inflammation.