생명과학회지 (Journal of Life Science)

  • 제19권6호
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  • Pages.818-824
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  • 2009
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  • 1225-9918(pISSN)
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  • 2287-3406(eISSN)
한국생명과학회 (Korean Society of Life Science)
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장의 허혈-재관류로 유도된 급성 폐손상에서 아스피린의 작용

Effect of Aspirin on the Acute Lung Injury Induced by Intestinal Ischemia/Reperfusion.

  • 박윤엽 (대구가톨릭대학교 의과대학 생리학교실)
  • Park, Yoon-Yub (Department of Physiology, School of Medicine, Catholic University of Daegu)
  • 발행 : 2009.06.30
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초록

급성 폐손상시 아스피린이 나타내는 염증 억제작용의 기전을 이해하기 위하여 쥐에서 장 허혈-재관류에 의한 급성 폐손상을 유발하여 phospholipase $A_{2}$ 억제제인 mepacrine과 아스피린의 효과를 비교하였다. 내독소 처치시 A549 세포와 RAW264.7 세포에서 cyc1ooxygenase-2 (COX-2)의 발현이 증가했는데, RAW264.7 세포의 반응이 더 크게 나타났다. 장의 허혈-재관류에 의해 장관 및 폐장조직에서 myeloperoxidase 활성도가 증가하여 염증성 호중구의 침윤이 증가했음을 보여 주었다. 조직 소견상에서도 조직 손상과 염증세포의 침윤이 관찰되었으며, 이는 아스피린 또는 mepacrine 전처치 시 억제 되었다. NADPH oxidase 억제작용이 있는 apocynin과 p38 MAPK 억제제인 SB203580은 A549 세포와 RAW264.7 세포의 LPS에 의한 COX-2 발현을 억제시켰으며 RAW264.7 세포에서 더 크게 억제되었다. 이상의 결과를 통해서 아스피린이 급성 폐손상의 예방목적으로 사용될 수 있다고 보여지며, RAW264.7 세포와 A549 세포에서 COX-2 발현은 다른 특성을 보여서 다른 조절기전이 있을 것으로 생각된다.

The mechanisms responsible for ischemia/reperfusion (I/R) injury have direct or indirect relevance to clinical lung injury after severe shock, cardiopulmonary bypass, and transplantation. This study investigated the effects of aspirin on intestinal I/R-induced acute lung injury (ALI) in rats. Lipopolysaccharide (LPS) induced cyclooxygenase-2 (COX-2) expression in A549 and RAW264.7 cells. RAW264.7 macrophages had shown greater expression of COX-2 than A549 cells. In addition, the NADPH oxidase inhibitor apocynin and p38 MAPK inhibitor SB203580 attenuated LPS-stimulated COX-2 expression. To induce ALI, intestinal ischemia was performed for 60 min prior to the 4 hr reperfusion by clamping the superior mesenteric artery in Sprague-Dawley rats. In order to test and compare the effect of non-specific COX inhibitor aspirin with the effect of mepacrine, a well known phospholipase$A_{2}$ inhibitor, rats were divided into 4 groups: Sham, I/R, Mepa+I/R (mepacrine, 60 mg/kg, i.p.), ASA+I/R (aspirin, 10 mg/kg, i.p.). In the present investigation, myeloperoxidase activities in the lung and intestinal tissues were increased by I/R. These changes were reduced by single pretreatment of mepacrine (60 mg/kg, i.p.) or aspirin (10 mg/kg, i.p.) 30 min before I/R. Structural studies demonstrated that the tissue injuries in the lung and intestine after I/R were also attenuated by the pretreatment of mepacrine or aspirin. These results suggest that I/R-induced ALI is mediated, in part, by the activation of COX. In addition, pretreatment of aspirin might be helpful for the prevention of ALI in ARDS-prone patients. In addition, the p38 MAPK inhibitor and apocynin also might be helpful to ALI through the inhibition of COX-2 expression.

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