Journal of Chest Surgery

The Korean Society for Thoracic and Cardiovascular Surgery (대한심장혈관흉부외과학회)
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The Effects of Nitric Oxide and Sphingosine 1-phosphate on the Pulmonary Microstructure in a Rat Model of Acute Lung Injury: An Intravital Videomicroscopic Approach

Nitric Oxide 및 Sphingosine 1-phosphate가 말초 호흡 단위에 미치는 영향의 생체 내 분석: 백서의 급성 폐 손상 모델에서 생체 접촉 현미경을 이용한 연구

  • Lee, Jae-Ik (Department of Thoracic and Cardiovascular Surgery, Gachon University Gil Hospital) ;
  • Jheon, Sang-Hoon (Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine) ;
  • Sung, Sook-Whan (Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine) ;
  • Kim, Joo-Hyun (Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, Seoul National University College of Medicine)
  • 이재익 (가천의과대학교 길병원 흉부외과학교실) ;
  • 전상훈 (서울대학교 의과대학 분당서울대학교병원 흉부외과학교실) ;
  • 성숙환 (서울대학교 의과대학 분당서울대학교병원 흉부외과학교실) ;
  • 김주현 (서울대학교 의과대학 서울대학교병원 흉부외과학교실)
  • Published : 2008.04.05
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Abstract

Background: To evaluate the effects of inhaled nitric oxide (NO) and sphingosine 1-phosphate (S1P) as potential therapeutic agents of acute lung injury, we analyzed the morphology in vivo of the pulmonary microstructure using intravital videomicroscopy in a rat model of acute lung injury. Material and Method: Sprague Dawley rats were divided into five groups: a control group that underwent normal saline aspiration, an acute lung injury (ALI) group that underwent hydrochloric acid aspiration, and three treatment groups that underwent hydrochloric acid aspiration and were administered therapeutic agents- the S1P group, the NO group, and the S1P+NO group (n=7 per group). To quantify alveolar compliance and interstitial edema, the diameters of all measurable alveoli and interalveolar septa were averaged at one and two hours after aspiration. Alveolar compliance was determined according to diameter changes during the respiratory cycle and the change in tidal volume. Result: At two hours after aspiration, the mean alveolar compliance (% change) in the All group decreased significantly versus the control group of rats (respiratory cycle: 1.9% for the ALI group vs 6.5% for the control group, p=0.03; tidal volume: 3.2% for the ALI group vs 9.1% for the control group, p=0.003) and versus the NO group (tidal volume: 3.2% for the ALI group vs 16.9% for the NO group, p=0.001). At two hours after aspiration, the mean interalveolar septal thickness in the NO group tended to be smaller as compared to that in the All group ($15.2{\mu}m$ for the ALI group vs $12.3{\mu}m$ for the NO group, p=0.06). S1P did not exert a significant effect on the pulmonary microstructure of the injured rat lung. Conclusion: Improved alveolar compliance and reduced interstitial edema, observed by intravital videomicroscopy, suggest that inhaled NO ameliorates lung injury.

배경: 이 연구에서는 급성 폐 손상 백서 모델에 nitric oxide (NO)와 sphingosine 1-phosphate (S1P)를 투여한 후, 폐 미세구조의 변화를 생체 접촉 현미경 (intravital videomicroscopy) 으로 생체 내에서 직접 관찰하고 형태학적으로 분석하여, 급성 폐 손상 치료법으로서 이들의 효과를 평가하고자 하였다. 대상 및 방법: 백서 (Sprague Dawley rat) 35마리를 5군으로 나누었다: 생리 식염수를 흡입시킨 대조군 (n=7), 0.1 N HCl을 흡입시켜 폐 손상을 유도한 폐 손상 대조군 (ALI 군, n=7), 폐 손상을 유도하고 치료제를 투여한 치료군 (S1P군, n=7; NO 군, n=7; S1P+NO군, n=7). 폐포 유순도와 간질성 부종의 정도를 평가하기 위해, 폐 손상 유도 후 60 분과 120분에 측정 가능한 모든 폐포와 폐포간 벽의 두께를 생체 접촉 현미경으로 측정하였다. 폐포 유순도는 호흡 주기에 따른 폐포 직경 변화와 일회 호흡량의 변화에 따른 직경 변화로 평가하였다. 결과: 폐 손상 유도 120분 후에, ALI 군의 폐포 유순도가 대조 군 (호흡 주기에 따른 변화 : ALI군 1.9% vs 대조군 6.5%, p=0.03; 일회 호홉량에 따른 변화: ALI군 3.2% vs 대조군 9.1%, p=0.003)과 NO군(일회 호흡량에 따른 변화: ALI군 3.2% vs NO군 16.9%, p=0.001)에 비해 의미 있게 감소하였다. 폐 손상 유도 120 분 후에, NO군의 폐포간 벽의 두께가 ALI군에 비해 작은 경향을 보였다 (ALI 군 $15.2{\mu}m$ vs NO군 $12.3{\mu}m$, p=0.06). S1P 단독으로는 폐포 유순도와 간질성 부종에 유의한 영향을 미치지 않았다. 결론: 백서 폐 손상 모델을 생체 접촉 현미경으로 관찰한 결과, NO는 폐포 유순도를 개선하고 간질성 부종을 감소시켜 폐 손상 정도를 완화시키는 것으로 사료된다.

Keywords

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