急性呼吸窘迫症候群(acute respiratory distress syndrome; ARDS)是一種由各式間接或直接性肺部傷害的發炎過程。臨床研究顯示，一氧化氮與前發炎細胞激素在急性肺部傷害的發生過程中扮演重要的角色。芝麻酚，是由芝麻油所萃取出的天然木質素；先前研究指出，芝麻酚能抑制脂多醣體誘導一氧化氮產生與一氧化氮合成酶蛋白質的表現及前發炎細胞激素的釋放，並減輕脂多醣體誘發的多器官功能失調；然而，芝麻酚對於脂多醣體所引起的急性肺部傷害的影響並不清楚。本研究的目的主要是探討芝麻酚對脂多醣體誘發急性肺部傷害的影響。實驗分為in vivo與ex vivo兩部分。在in vivo中，以腹腔注射脂多醣體（5 mg/kg）來誘導Wistar實驗大鼠之急性肺部發炎，同時以皮下注射給予芝麻酚（10 mg/kg），並於12小時後取得肺臟及肺泡沖出液做分析。結果顯示，芝麻酚明顯減少肺臟水腫、一氧化氮的產生、一氧化氮合成酶蛋白質的表現、以及發炎細胞的浸潤。在ex vivo部分，芝麻酚能明顯抑制脂多醣(100 ng/ml)引發初代肺泡巨噬細胞一氧化氮的生成、一氧化氮合成酶蛋白質的表現、以及前發炎細胞激素的產生。因此，芝麻酚降低脂多醣體引發的肺部傷害，可能與其對一氧化氮合成酶及前發炎細胞激素的抑制有關。

Acute respiratory distress syndrome (ARDS) is an inflammatory process caused by a variety of direct and indirect injuries to the lungs. Clinical studies indicate that nitric oxide (NO) and pro-inflammatory cytokines are involved in the pathogenesis of ARDS. Sesamol, one of the lignans in sesame oil, has been reported to reduce nitric oxide production and inducible NO synthase (iNOS) expression, and attenuate multiple organ failure during endotoxemia. However, the effect of sesamol on LPS-induced acute pulmonary injury has never been investigated. The aim of this study was to examine the effects of sesamol on LPS-induced acute pulmonary inflammation in rats. Acute pulmonary inflammation was induced by LPS (5 mg/kg, intraperitoneally) in Wistar rats. Sesamol (10 mg/kg, subcutaneously) was given just after LPS administration. Pulmonary edema, myeloperoxidase (MPO) activity, NO production, and iNOS expression were assessed 12 h after sesamol. Sesamol decreased pulmonary edema, MPO activity, NO production, and iNOS expression. Further, sesamol dose-dependently inhibited LPS (100 ng/kg)-stimulated NO production, iNOS expression, and pro-inflammatory cytokine generation in primary alveolar macrophages. It is suggested that the inhibitions of iNOS expression and pro-inflammatory cytokine production might be associated with sesamol-exerted anti-inflammation in LPS-induced acute pulmonary inflammation, at least partially.

參考文獻
Abel SJC, Finney SJ, Brett SJ, Keogh BF, Morgan CJ, Evans TW.
Reduced mortality in associtation with the acute respiratory distress
syndrome (ARDS). Thorax 53: 292-294, 1998.
Aderem A. How to eat something bgger than your head. Cell 110:5-8,
2002.
Allen GS, COX CSJR. Pulmonary contusion in children:diagnosis and
management. The Southern Medical Journal 91:1099-1106, 1998.
Ambrosino N. Noninvasive mechanical ventilation in acute respiratory
failure. The European Respiratory Journal 9:795-807, 1996.
Ando K, Sako KI, Takahashi M, Beppu M, Kikugawa K. Increased band
3 protein aggregation and anti-band 3 binding of erythrocyte
membrane on treatment with sesamol. Biological &
Pharmaceutical Bulletin 23:159-164, 2000.
Anthony E. Redington. Modulation of nitric oxide pathways: Therapeutic
potential in asthma and chronic obstructive pulmonary disease.
European Journal of Pharmacology 263-276, 2006.
Anxueto A, Baughman RP, Guntupalli KK, Weg JG, Zaccardelli DS,
Pattishall EN. Aerosolized surfactant in adults with sepsis-induced
acute respiratory distress syndrome. Exosurf acute respiratory
distress syndrome sepsis study group. The New England Journal of
Medicine 334:1417-1421, 1996.
Aoyagi K, Akiyama K, Shahrzad S, Tomida C, Hirayama A, Nagase S.
Takemura K, Koyama A, Ohba S, Narita M. formation of
guanidinosuccinic acid, a stable nitric oxide minic, from
arginiosuccinic and nitric oxide-derived free radicals. Free radical
research 31:59-65, 1999.
Arkovitz, M. S., J. R. Wispe, V.F. Garcia, and C. Szabo. Selective
inhibition of the inducible isoform of nitric oxide synthase prevents
pulmonary transvascular flux during acute endotoxemia. Journal of
Pediatric Surgery. 31:1009-1015.
Arnold S. Kristof, Peter Goldberg, Victor Laubach and Sabah N. A.
Hussain. Role of inducible nitric oxide synthase in
endotoxin-induced acute lung injury. American Journal of Critical
Care Medicine 158:1883-1889,1998.
Ashbaugh DG, Bigelow DB, Petty TL, Levine BE. Acute respiratory
distress in adults. Lancet 2:319-323, 1967.
Bando K, Pillai R, Cameron DE, Brawn JD, Winkelstein JA, Hutchins
GM, Reitz BA, Baumgartner WA. Leukocyte depletion ameliorates
free radical-mediated lung injury after cardiopulmonary bypass.
The Journal of Thoracic and Cardiovascular Surgery 99:873-877,
1990.
Beckman, J. S., and W. H. Koppenol. Nitric oxide, superoxide, and
peroxynitrite: the good, the bad, and the ugly. American Journal of
Physiology 271::c1424-c1437, 1997.
Bernard GR, Artigas A, Brigham KL, Carlet J, Falke K, Hudson L,
Lamy M, LeGall JR, Morris A, Spragg R. Report of the
American-European consenseus conference on ARDS: definitions,
mechanisms, relevant outcomes and clinical trial coordination. The
Consensus Committee. Intensive Care Medicine 20:225-322, 1994.
Blanch L, Mancebo J, Perez M, Martinez M, Mas A, Betbese AJ, Joseph
D, Ballus J, Lucangelo U, Bak E. Short-term effects of prone
position in critically ill patients with acute respiratory distress
syndrome. Intensive Care Medicine 23:1033-1039, 1997.
Bloomfield, G. L., S. Holloway, P. C. Ridings, B. J. Fisher, C. R. Blocher,
M. Sholley, T. Bunch, H. J. Sugerman, and A. A. Fowler.
Pretreatment with inhaled nitric oxide inhibits neutrophil migration
and oxidative activity resulting in attenuated sepsis induced acute
lung injury. Critical Care Medicine 25:584-593, 1997.
Bone RC, Slotman G, Maunder R, et al., Prostaglandin E1 study group.
Randomized double-blind, multicenter sudy of prostaglandin E1 in
patients wit acute respiratory distress syndrome. Chest 96:114-119,
1989.
Budowski P. Recent research on sesamin, sesamolin and related
compound. Journal of the American Oil Chemists' Society
41:280-285, 1964.
Chavali SR, Utsunomiya T, Forse RA. Increased survival after cecal
ligatin and puncture in mice consuming diets enriched with sesame
seed oil. Critical Care Medicine 29:140-143, 2001.
Chen CS, Perng WC, Chen CW, Huang KL, Wu CP, Yen MH.
Thalidomide reduces lipopolysaccharide/zymosan-induced acute
lung injury in rats. Journal of Biomedical Science 11:591-598,
2004.
Collins RH, Feldman M, Fortran JS. Colon cancer, dysplasia and
surveillance in patients with ulterative colitis: a critical review.
New England Journal of Medicine. 316:1654-1658, 1987.
Conference report. Mechanisms of acute respiratory failure. The
American Review of Respiratory Disease 115:1071-1078, 1977.
Dalloz F, Maupoil V, Lecour S, Briot F, Rochette L. In vitro studies of
interactions of NO donor drugs with superoxide and hydroxyl
radicals. Molecular and cellular biochemistry 177:193-200, 1997.
Dellinger RP, Zimmerman JL, Taylor RW et al., Inhaled nitric oxide in
ARDS study group. Effets of inhaled nitric oxide in patients with
acute respiratory ditstress syndrome: results of a randomized phase
II trial. Critical Care Medicine 26:15-23, 1998.
Dematte J, Barnard M, Sznajder J. Accute respiratoyr failure in sepsis.
Sepsis and Multiorgan Failure 1997.
Downey GP, Dong Q, Kruger J, Dedhar S, Cherapanov V. Regulation of
neutrophil activation in acute lung injury. Chest 116:46-54, 1999.
Frostell CG, Fratacci MD, Wain JF, Jones R, Zapol WM. Inhaled nitric
oxide: A selective pulmonary vasodilator reversing hypoxic
pulmonary vasoconstriction Circulation 83: 2038-2047, 1991.
Fullerton DA, Eisenach JH, Mclntyre RC Jr, Friese RS, Sheridan BC,
Roe GB, Agrafojo J, Banerjee A, Harken AH. Inhaled nitric oxide
prevents pulmonary endothelial dysfunction after mesenteric
ischemia-reperfusion. The American Journal of Physiology
271:326-331,1996.
Haddad, I Y., G, Pataki, C. Galliani, J S. Beckman, and S. Matalon.
Quantitation of nitrotyrosine levels in lung sections of patients and
animals with acute lung injury. The Journal of Clinical
investigation 94:2407-2413, 1994.
Hammer J. Acute lung injury: pathophysiology, assessment and current
therapy. Paediatric Respiratory Reviews 2:10-21, 2000.
Heremans H, Dillen C, Groene M, Matthys P, Billiau A. Role of
interon-gamma and nitric oxide in pulmonary edema and death
induced by lipopolysaccharide. American Journal of Respiratory
and Critical Care Medicine 161:110-117, 2000.
Hernan LJ, Fuhrman BP, Papo MC, Steinhorn DM, Leach CL, Salman N,
Paczan PR, Kahn B. Cardiorespiratory effects of
perfluorocarbon-associated gas exchange at reduced oxygen
concentrations. Critical Care Medicine 23:553-559, 1995.
Hickey MJ, Sihota E, Amrani A, Santamaria P, Zbytnuik LD, Ng ES, Ho
W, Sharkey KA, Kubes P. Inducible nitric oxide synthase (iNOS) in
endotoxemia: chimeric mice reveal different cellular sources in
various tissues. The FASEB journal 16:1141-1143, 2002.
Hirschl RB, Conrad S, Kaiser R, Zwischenberger JB, Bartlett RH, Booth
F, Cardenas V. Partial liquid ventilation in adult patients with
ARDS: a multicenter phase l-11 trial. Adult PLV study group.
Annals of Surgery 228:692-700, 1998.
Hirschl RB, Parent A, Tooley R, McCracken M, Johnson K, Shaffer TH,
Wolfson MR, Bartlett RH. Liquid ventilation improves pulmonary
function, gas exchange, and lung injury in a model of respiratory
failure. Annals of Surgery 221:79-88, 1995.
Holcroft JW, Vassar MJ, Weber CJ. Prostaglandin E1 and survival in
patients with the adult respiratory distress syndrome: a prospective
trial. Annals of Surgery 203:371-378, 1986.
Hsu DZ, Li YH, Chu PY, Chien SP, Chung YC, Liu MY. Attenuation of
endotoxin-induced oxidative stress and multiple organ injury by
3,4-methylenedioxyphenol in rats. Shock 25:300-305, 2006.
Iuvone, T., F. D’Aquisto, T. Carnuccio, and M. Di Rosa. Nitric oxide
inhibits LPS-induced tumor necrosis factor synthesis in vitro and in
vivo. Life Sciences 59:207-211, 1996.
Jaffray C, Yang J, Carter G, Mendez C, Norman J. Pancreatic elastase
activates pulmonary nuclear factor kappa B and inhibitory kappa B,
mimicking pancreatitis-associated adulted respiratory distress
syndrome. Surgery. 128:225-231, 2000.
Kang MH, Naito M, Tsujihara N, Osawa T. Sesamolin inhibits lipid
peroxidation in rat liver and kidney. The Journal of Nutrition
128:1018-1022, 1998.
Kaur IP, SainiA. Sesamol exhibits antimutagenic activity against oxygen
Species mediated mutagenicity. Mutation Research 470:71-76,
2000.
Kaboyashi A, Hashimoto S, Koouchi K, Kitamura Y, Onodera H, UrataY,
AshiharaT. Expression of inducible nitric oxide synthase and
inflammatory cytokines in alveolar macrophages of ARDS
following sepsis. Chest 113:1632-1639, 1998.
Kobashi Y, Manabe T. The fibrosing process in so called organized
diffuse alveolar damage. Virchows Archives 422:47-52, 1993.
Krafft P, Fridrich P, Fitzgerald RD. Effectiveness of nitric oxide
inhalation in septic ARDS. Chest 109: 486-493, 1996.
Lamm WJ, Graham MM, Albert RK. Mechanism by which the prone
Position improves oxygenation in acute lung injury. American
Journal of Respiratory and Critical Care Medicine 150:184-193,
1994.
Lee PC, Helsmoortel CM, Cohn SM, Fink MP. Are low tridal volumes
safe? Chest 97:430-434, 1990.
Marcy TW, Marini JJ. Inverse ratio ventilation in ARDS. Rationale and
implementation. Chest 100:494-504, 1991.
Matthay MA and Zommerman GA. Acute lung injury and the acute
respiratory distress syndrome: Four decades of inquiry into
pathogenesis and rational management. American Journal of
Respiratory Cell and Molecular Biology 33:319-327, 2005.
Mattay MA. The acute respiratory distress syndrome. The New England
Journal of Medicine 334: 1469-1470, 1996.
Mellor A. Soni N. Fat embolism. Amaesthesia 56:145-54, 2001.
Mikawa K, Akamatsu H, Maekawa N, Nishina K, Obara H, Niwa Y.
Inhibitory effect of prostaglandin E1 on human neutrophil function.
Prostaglandins, Leukotrienes, and Essential Fatty Acids 51: 287
-297, 1994.
Milberg JA, Davis DR, Steinberg KP, Hudson LD. Improved survival of
patients with acute respiratory distress syndrome (ARDS)
:1983-1993. JAMA 273:306-309, 1995.
Moncada S, Higgs A. Mechanisms of disease: the L-arginine-nitric oxide
pathway. The New England Journal of Medicine 329:2002-2012,
1993.
Montgomery AB, Stager MA, Carrico CJ, Hudson LD. Causes of
mortality in patients with the adult respiratory distress syndrome.
The American Review of Respiratory Disease 132:485-489, 1985.
Moss M, Parsons PE. Mechanical ventilation and the adult respiratory
distress syndrome. Seminars in Respiratory and Critical Care
Medicine 15:289-299, 1994.
Murray JF, Matthay MA Luce JM, Flick MR. An expanded definition of
the adult respiratory distress syndrome. American Journal of
Respiratory and Critical Caremedicine 138:720-723, 1988.
Nathan CF. Macrophage activation: some questions. Annales de l'Institut
Pasteur. Immunologie 137C:345-351, 1986.
Neviere R, Mordon S, Marechal X, Buys B, Guery B, Mathieu D, Wattel
F, Chopin C. Inhaled nitric oxide modulates leukocyte kinetics in
the mesenteric venules of endotoxemic rats. Critical Care Medicine
28: 1072-1076, 2000.
Obata T. Nitric oxide and depolarization induce hydroxyl radical
generation. Japanese journal of pharmacology 88:1-5, 2002.
Pheng, L. H., C. Francoeur, and M. Denis. The involvement of nitric
oxide in a mouse model of adult respiratory distress syndrome.
Inflammation 19:599-610.
Raksha Jain, MD and Anthony Dalnogare, MD. Pharmacological therapy
for acute respiratory distress syndrome. Mayo Foundation for
Medical Education and Research 81:205-212, 2006.
Rocker GM, Wiseman MS, Perason D, Shale DJ. Diagnostric criteria for
adult respiratory distress syndrome: time for reappraisal. Lancet
1:120-123,1989.
Rossaint R, Falke KJ, Lopez F, Slama K, Pison U, Zapol WM. Inhaled
nitric oxide for the adult respiratory distress syndrome. The New
England Journal of Medicine 328: 399-405, 1993.
Schwarz MA. Acute lung injury: cellular mechanisms and derangements.
Paediatric Respiratory Reviews 2:3-9, 2001.
Shaffer TH, Wolfson MR, Clark LC Jr. Liquid ventilation. Pediatric
Pulmonology 14:102-109, 1992.
Sharar SR, Winn RK, Harlan JM. Endotoxin-induced interatctions of
inflammatory cels with the lung. New York, pp. 229-265, 1994.
Suwabe A Otake K, Yakuwa N, Suzuki H, Ito M, Tomoike H, Saito Y,
Takahashi K. Artificiall surfactant (Surfactant TA) modulates
adherence and superoxide production of neutrophils. American
Journal of Respiratory and Critical Care Medicine 158:1890-1899,
1998.
Tasaka, S , Hasegawa N, Ishizaka A. Pharmacology of acute lung injury.
Pulmonary Pharmacology & Therapeutics 15:83-95, 2002.
Thomassen MJ, Antal JM, Barna BP, Divis LT, Meeker DP, Wiedemann
HP. Surfactant downregulates synthesis of DNA and inflammatory
mediators in normal human lung fibroblast. The American Journal
of Physiology 270:159-163, 1996.
Thomassen MJ, Antal JM, Divis LT, Wiedemann HP. Regulation of
human alveolar macrophate inflammatory cytokines by tyloxapol: a
component of the synthetic surfactant exosurf. Clinical
Immunology and Immunopathology 77:201-205, 1995.
Troncy E, Collet P, Shapiro S. Inhaled nitric oxide in acute respiratory
distress syndrome: a pilot randomized controlled study. American
Journal of Respiratory and Critical Care Medicine 157:
1483-1488, 1998.
Uchida M, Nakajin S, Toyoshima S, Shinoda M. Antioxidative effect of
sesamol and related compounds on lipid peroxidation. Biological &
Pharmaceutical Bulletin 19:623-626, 1996.
Valta P, Takala J. Volume-controlled inverse ratio ventilation: effect on
dynamic hyperinflation and auto PEEP. Acta Anaesthesiologica
Scandinavica.37:323-328, 1993.
Vassalli P. The pathophysilogy of tumor necrosis factors. Annual Review
Of Immunology 10:411-452, 1992.
Wang D, Wei J, Hsu K, Jau J, Lieu MW, Chao TJ, Chen HI. Effects of
nitric oxide synthase inhibitor expression and lung injury
following endotoxin administratin in rats. Journal of Biomedical
Science 6:28-35, 1999.
Wang LF, Patel M, Razavi HM, Weicker S, Joseph MG, McCormack DG,
Mehta S. Role of inducible nitric oxide synthase in pulmonary
microvascular protein leak in murine sepsis. American Journal of
Critical Care Medicine 165:1634-1639, 2002.
Ware LB, Matthay MA. The acute respiratory distress syndrome. The
New England Journal of Medicine 342:1334-1349, 2000.
Wizemann, T. M., C. R. Gardiner, J. D. Laskin, S. Quinones, S. K.
Durham, N. L. Goller, S. T. Ohnishi, and D. L. Laskin. Production
of nitric oxide and peroxynitrite in the lung during endotoxemia.
Journal of Leukocyte Biology 56:759-768, 1994.
Zavala E, Ferrer M, Polese G, Masclans JR, Planas M, Milic-Emili J,
Rodriguez-Roisin R, Roca J, Rossi A. Effect of inverse I:E ratio
ventilation on pulmonary gase exchange in acute respiratory distress
syndrome. Anesthesiology 88:35-42, 1998.