The Efficacy of α-lipoic Acid on the Endotoxin-induced Acute Lung Injury

α-lipoic acid 후처치가 내독소로 유발된 급성폐손상에 미치는 효과

  • Huh, Jin Won (Department of Internal Medicine, Ilsan Paik Hospital, Inje University) ;
  • Hong, Sang Bum (Division of Pulmonary and Critical Care Medicine, Asan Medical Center, University of ulsan College of Medicine) ;
  • Kim, Mi Jung (Asan Institute for Life Sciences) ;
  • Lim, Chae-Man (Division of Pulmonary and Critical Care Medicine, Asan Medical Center, University of ulsan College of Medicine) ;
  • Koh, Younsuck (Division of Pulmonary and Critical Care Medicine, Asan Medical Center, University of ulsan College of Medicine)
  • 허진원 (인제대학교 일산백병원 내과학교실) ;
  • 홍상범 (울산대학교 의과대학 서울아산병원 호흡기내과) ;
  • 김미정 (아산생명과학연구소) ;
  • 임채만 (울산대학교 의과대학 서울아산병원 호흡기내과) ;
  • 고윤석 (울산대학교 의과대학 서울아산병원 호흡기내과)
  • Received : 2006.12.11
  • Accepted : 2007.02.09
  • Published : 2007.02.28

Abstract

Background: Oxidative stress may play an important role in the pathogenesis of endotoxin-induced acute lung injury (ALI). This study evaluated the therapeutic effect of ${\alpha}$-lipoic acid, a nonenzymatic antioxidant, in a rat model of lipopolysaccharide (LPS) induced ALI. Materials and Methods: ALI was induced in Sprague-Dawley rats by instilling LPS (E.coli, 3mg/Kg) into the trachea. The rats were classified into the control, control+${\alpha}$-lipoic acid, LPS, and LPS+${\alpha}$-lipoic acid groups.The lung lavage neutrophil count, cytokine-induced neutrophil chemoattractant (CINC), lung myeloperoxidase (MPO), and cytokine concentrations (TNF-${\alpha}$, IL-$1{\beta}$, IL-6 and IL-10) were measured at 2 h and 6 h after LPS administration. Results: The total cell and neutrophil counts of the LPS+${\alpha}$-lipoic acid groups were significantly lower than the LPS groups. The protein concentration in the BAL fluid was similar in the LPS groups and LPS+${\alpha}$-lipoic acid groups. The TNF-${\alpha}$, IL-$1{\beta}$, and IL-6 concentrations in the BAL fluid were not decreased by the ${\alpha}$-lipoic acid treatment in the LPS treated rats. Conclusions: Although ${\alpha}$-lipoic acid decreased the level of LPS-induced neutrophil infiltration into the lung, it could not attenuate the LPS-induced ALI at the dose administered in this study.

연구배경: 내독소로 유발된 급성폐손상의 발생기 전에 산화스트레스가 중요한 역할은 한다. 본 실험은 LPS로 유발한 급성폐손상 모델에서 항산화제인 ${\alpha}$-lipoic acid의 치료효과를 보고하였다. 방 법: Sprague-Dawley 쥐를 대상으로 LPS(E.coli, 3mg/Kg)를 기도내 주입 후 ${\alpha}$-lipoic acid를 복강 내 주입하였다. 2시간, 6시간 후에 폐포세척액에서 호중구수, CINC, 시토카인의 농도를 구하고 폐조직에서 MPO를 측정하였다. 결 과: ${\alpha}$-lipoic acid를 후처치한 군에서 LPS 단독군보다 2시간 뒤와 6시간 뒤에 총 세포수와 호중구의 수가 감소하였으나 단백질 농도는 차이가 없었다. 또한 염증성 인자인 TNF-${\alpha}$, IL-$1{\beta}$, IL-6의 농도도 ${\alpha}$-lipoic acid 처치군에서 유의한 감소를 보이지 못하였다. 결 론: LPS 로 급성폐손상 유도 모델에서 ${\alpha}$-lipoic acid의 후처치는 폐장내로의 호중구의 침윤은 억제할 수 있지만 급성폐손상을 약화시키지는 못 하였다.

Keywords

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