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World Journal of Surgery

, Volume 34, Issue 7, pp 1676–1683 | Cite as

Histone Deacetylase Inhibitors Attenuate Acute Lung Injury During Cecal Ligation and Puncture-Induced Polymicrobial Sepsis

  • Li Zhang
  • Shengwei Jin
  • Changdong Wang
  • Rong Jiang
  • Jingyuan Wan
Article

Abstract

Background

The histone deacetylase (HDAC) inhibitors have emerged as the useful reagents that epigenetically modulate the expression of various genes. In the present study, the effects of HDAC inhibitors on the expression of inflammation-related genes and lung injury during sepsis were investigated.

Methods

Mice were pretreated with two structurally unrelated HDAC inhibitors, Trichostatin A (TSA) and sodium butyrate (SB). Thirty minutes later, mice underwent cecal ligation and puncture (CLP)-induced sepsis. Lung injury and the expression of inflammation-related molecules were determined. In addition, survival was assessed post-CLP.

Results

Our results indicated that administration of TSA or SB alleviated sepsis-induced lung injury. This was accompanied by reduced neutrophil infiltration, decreased intercellular adhesion molecule-1 (ICAM-1) and E-selectin expression in lung tissue, and lower interleukin-6 (IL-6) level in plasma. In addition, treatment with HDAC inhibitors significantly prolonged the survival time of CLP mice.

Conclusions

These data indicated that the HDAC inhibitors, based on modulating the key enzymes linked to acetylation modification, effectively attenuate intrapulmonary inflammatory response, thus significantly alleviating lung injury during sepsis.

Keywords

Lung Injury HDAC Inhibitor Sodium Butyrate Sodium Butyrate Polymicrobial Sepsis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (Nos. 30772088 and 30900651) and the Chongqing Municipal Education Commission (No. KJ090304).

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Copyright information

© Société Internationale de Chirurgie 2010

Authors and Affiliations

  • Li Zhang
    • 1
  • Shengwei Jin
    • 2
  • Changdong Wang
    • 3
  • Rong Jiang
    • 4
  • Jingyuan Wan
    • 5
  1. 1.Department of Pathophysiology, Laboratory of Stem Cell and Tissue EngineeringChongqing Medical UniversityChongqingChina
  2. 2.Department of Anesthesiology, Second Affiliated HospitalWenzhou Medical CollegeWenzhouChina
  3. 3.Department of Biochemistry and Molecular BiologyChongqing Medical UniversityChongqingChina
  4. 4.Laboratory of Stem Cell and Tissue EngineeringChongqing Medical UniversityChongqingChina
  5. 5.Department of PharmacologyChongqing Medical UniversityChongqingChina

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