Tuberculosis and Respiratory Diseases

The Korean Academy of Tuberculosis and Respiratory Diseases (대한결핵및호흡기학회)
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The Effects of Ethyl Pyruvate on Lipopolysaccharide-induced Acute Lung Injury

리포다당질에 의한 급성폐손상에서 Ethyl Pyruvate의 효과

  • Lee, Seung Hyeun (Department of Internal Medicine, College of Medicine, Korea University) ;
  • Yoon, Dae Wui (Institute of Human Genomic Study, Ansan Hospital, Korea University Medical Center) ;
  • Jung, Jin Yong (Department of Internal Medicine, College of Medicine, Korea University) ;
  • Lee, Kyung Joo (Department of Internal Medicine, College of Medicine, Korea University) ;
  • Kim, Se Joong (Department of Internal Medicine, College of Medicine, Korea University) ;
  • Lee, Eun Joo (Department of Internal Medicine, College of Medicine, Korea University) ;
  • Kang, Eun Hae (Department of Internal Medicine, College of Medicine, Korea University) ;
  • Jung, Ki Hwan (Department of Internal Medicine, College of Medicine, Korea University) ;
  • Lee, Sung Yong (Department of Internal Medicine, College of Medicine, Korea University) ;
  • Lee, Sang Yeub (Department of Internal Medicine, College of Medicine, Korea University) ;
  • Kim, Je Hyeong (Department of Internal Medicine, College of Medicine, Korea University) ;
  • Shin, Chol (Department of Internal Medicine, College of Medicine, Korea University) ;
  • Shim, Jae Jeong (Department of Internal Medicine, College of Medicine, Korea University) ;
  • In, Kwang Ho (Department of Internal Medicine, College of Medicine, Korea University) ;
  • Kang, Kyung Ho (Department of Internal Medicine, College of Medicine, Korea University) ;
  • Yoo, Se Hwa (Department of Internal Medicine, College of Medicine, Korea University)
  • 이승현 (고려대학교 의과대학 내과학교실) ;
  • 윤대위 (고려대학교의료원 안산병원 인간유전체연구소) ;
  • 정진용 (고려대학교 의과대학 내과학교실) ;
  • 이경주 (고려대학교 의과대학 내과학교실) ;
  • 김세중 (고려대학교 의과대학 내과학교실) ;
  • 이은주 (고려대학교 의과대학 내과학교실) ;
  • 강은해 (고려대학교 의과대학 내과학교실) ;
  • 정기환 (고려대학교 의과대학 내과학교실) ;
  • 이승룡 (고려대학교 의과대학 내과학교실) ;
  • 이상엽 (고려대학교 의과대학 내과학교실) ;
  • 김제형 (고려대학교 의과대학 내과학교실) ;
  • 신철 (고려대학교 의과대학 내과학교실) ;
  • 심재정 (고려대학교 의과대학 내과학교실) ;
  • 인광호 (고려대학교 의과대학 내과학교실) ;
  • 강경호 (고려대학교 의과대학 내과학교실) ;
  • 유세화 (고려대학교 의과대학 내과학교실)
  • Received : 2006.07.19
  • Accepted : 2006.09.18
  • Published : 2006.10.30
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Abstract

Background: Ethyl pyruvate (EP) is a derivative of pyruvate that has recently been identified by both various in vitro and in vivo studies to have antioxidant and anti-inflammatory effects. The aim of this study was to determine the effect of EP on lipopolysaccharide (LPS)-induced acute lung injury (ALI). Methods: 5 weeks old, male BALB/c mice were used. ALI was induced by an intratracheal instillation of LPS 0.5mg/Kg/$50{\mu}L$ of saline. The mice were divided into the control, LPS, EP+LPS, and LPS+EP groups. In the control group, balanced salt solution was injected intraperitoneally 30 minutes before or 9 hours after the intratracheal instillation of saline. In the LPS group, a balanced salt solution was also injected intraperitoneally 30 minutes before or 9 hours after instillation the LPS. In the EP+LPS group, 40mg/Kg of EP was injected 30 minutes before LPS instillation. In the LPS+EP group, 40mg/Kg of EP was injected 9 hours after LPS instillation. The TNF-$\alpha$ and IL-6 concentrations in the bronchoalveolar lavage fluid (BALF), and that of NF-$\kappa$B in the lung tissue were measured in the control, LPS and EP+LPS groups at 6 hours after instillation of saline or LPS, and the ALI score and myeloperoxidase (MPO) activity were measured in all four groups 24 and 48 hours after LPS instillation, respectively. Results: The TNF-$\alpha$ and IL-6 concentrations were significantly lower in the EP+LPS group than in the LPS group (p<0.05). The changes in the concentration of these inflammatory cytokines were strongly correlated with that of NF-$\kappa$B (p<0.01). The ALI scores were significantly lower in the EP+LPS and LPS+EP groups compared with the LPS group (p<0.05). In the EP+LPS group, the MPO activity was significantly lower than the LPS group (p=0.019). Conclusion: EP, either administered before or after LPS instillation, has protective effects against the pathogenesis of LPS-induced ALI. EP has potential theurapeutic effects on LPS-induced ALI.

연구배경: 급성폐손상에서 활성산소종에 의한 산화 손상은 주요한 역할을 한다. Ethyl pyruvate (EP) 는 체내에서 생성되는 pyruvate의 유도체로 항산화 및 항염증 효과가 있음이 알려졌다. 저자들은 리포다당질에 의한 급성폐손상 모델에서 EP가 염증반응에 미치는 영향을 연구하고자 하였다. 방 법: 5주 령의 BALB/c 생쥐를 이용하여 리포다당질을 기관 내로 투여하여 급성폐손상을 유도하였다. 대조군, LPS군, EP+LPS군, LPS+EP군으로 나누어 기관지폐포세척액에서 TNF-$\alpha$, IL-6 및 myeloperoxidase (MPO)의 활성을, 폐조직에서 급성폐손상 지수와 NF-$\kappa$B의 농도를 측정하였다. 결 과: EP+LPS군에서 TNF-$\alpha$ 및 IL-6의 농도는 LPS군과 비교하여 감소하였고 (p<0.05) 이들 염증성 시토카인의 농도의 변화는 NF-$\kappa$B의 농도의 변화와 상관 관계를 보였다 (p<0.01). 급성폐손상 지수는 EP+LPS군 및 LPS+EP군에서 LPS군과 비교하여 낮았고 (p<0.05) MPO활성은 EP+LPS군에서 LPS군에 비해 낮았다 (p<0.05). 결 론: EP는 LPS로 인한 급성폐손상에 있어서 예방 및 치료 효과가 있는 것으로 판단된다.

Keywords

References

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