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Cecal Ligation and Puncture-induced Sepsis as a Model To Study Autophagy in Mice
06:40

Cecal Ligation and Puncture-induced Sepsis as a Model To Study Autophagy in Mice

Published on: February 9, 2014

Enhancing autophagy with activated protein C and rapamycin protects against sepsis-induced acute lung injury

Yu-Ting Yen1, Hong-Ren Yang, Hung-Chieh Lo

  • 1Department of Acute Care Surgery, China Medical University, Taichung, Taiwan.

Surgery
|February 26, 2013
PubMed
Abstract

Insights

Sepsis suppresses autophagy, increasing lung injury and inflammation. Enhancing autophagy with rapamycin or activated protein C (APC) improves survival in sepsis-induced acute lung injury (ALI).

Area of Science:

  • Cellular Biology
  • Immunology
  • Pathophysiology

Background:

  • Autophagy is crucial in regulating apoptosis and inflammation.
  • Sepsis-induced acute lung injury (ALI) involves complex inflammatory and apoptotic processes.
  • Investigating autophagy's role in ALI is key for novel therapeutic development.

Purpose of the Study:

  • To investigate autophagy regulation in septic lungs.
  • To assess the functional significance of modulating autophagy using pharmacologic agents.
  • To explore therapeutic strategies for sepsis-induced ALI.

Main Methods:

  • Mice underwent cecal ligation and puncture (CLP) or sham surgery.
  • Pharmacologic agents (rapamycin, activated protein C [APC], bafilomycin A1) were administered post-CLP.
  • Lung tissue and survival were analyzed at various time points.

Main Results:

  • CLP induced systemic inflammation, decreased survival, and increased lung leukocyte infiltration, inflammation, and apoptosis.
  • Autophagy was suppressed post-CLP, evidenced by downregulated LC3II, Atg5, and Rab7.
  • Rapamycin and APC treatments activated autophagy, reduced inflammation, and decreased apoptosis, significantly improving 7-day survival.

Conclusions:

  • Autophagy downregulation contributes to sepsis-induced systemic inflammation and ALI.
  • Modulating autophagy, either directly (rapamycin) or indirectly (APC), enhances survival.
  • Early enhancement or restoration of autophagy presents a promising therapeutic strategy for sepsis-induced ALI.

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