Propofol exerts protective effects on the acute lung injury induced by endotoxin in rats

被引:41
作者
Chu, Chia-Hsiang
Liu, Demeral David
Hsu, Yung-Hsiang
Lee, Kuan-Chiao
Chen, Hsing I.
机构
[1] Tzu Chi Hosp, Dept Pediat, Hualien, Taiwan
[2] Tzu Chi Hosp, Dept Dent, Hualien, Taiwan
[3] Tzu Chi Hosp, Inst Med Sci, Hualien, Taiwan
[4] Tzu Chi Hosp, Neuromed Sci Ctr, Hualien, Taiwan
[5] Tzu Chi Hosp, Dept Pathol, Hualien, Taiwan
[6] Tzu Chi Hosp, Dept Med, Hualien, Taiwan
[7] Tzu Chi Hosp, Inst Integrat Physiol & Clin Sci, Hualien, Taiwan
关键词
Endotoxemia; pro-inflainmatory cytokines; nitric oxide; microvascular permeability;
D O I
10.1016/j.pupt.2006.03.006
中图分类号
R9 [药学];
学科分类号
1007 [药学];
摘要
Acute lung injury (ALI) is a major culprit of mortality in endotoxemia. Propofol has been commonly used in critical ill patients for sedation. This experiment attempted to elucidate the effects and possible mechanisms of propofol on the ALI induced by endotoxin. Experimentations were carried Out Using anesthetized, ventilated rats and isolated perfused rat lungs. Endotoxemia was induced by intravenous lipopolysaccharide (LPS, 10 mg kg(-1)). Various groups of rats received infusion of physiological saline solution (PSS) and LPS. Five min after LPS, propofol at low dose(5 mg kg(-1) h(-1)) or high dose (10 mg kg(-1) h(-1)) was infused for 6h. In isolated perfused rat lungs, PSS, LPS, and propofol (30 or 60 mg kg(-1)) were added into the perfusion circuit. During or after 6h observation, we determined the lung weight (LW)/body weight ratio, LW gain, exhaled nitric oxide (NO) and protein concentration in broncheoalveolar lavage. Lung pathology was evaluated to quantify the lung injury score. Plasma nitrate/nitrite, methyl guanidine (MG), tumor necrosis factor(alpha), and interleukin-1(beta) were examined. Blood leukocytes were counted. Capillary filtration coefficient (K-fc) was obtained in isolated perfused lungs. Posttreatment of propofol at low or high dose attenuated or prevented the extent of ALI. It also reduced the plasma nitrate/nitrite, MG. and pro-inflammatory cytokines including tumor necrosis factor(alpha) (TNF alpha) and interleukin-1(beta) (IL-1(beta)). In the isolated perfused rat lungs, propofol significantly reduced the LPS-induced increase in K-fc. This agent did not affect the leukocytopenia caused by LPS. Accordingly, the effects of propofol on the ALI were not related to leukocyte activation or sequestration. Our results suggest that propofol exerts protective effect on the endotoxin-induced ALI. The mechanisms of actions may be mediated through inhibition on the release of pro-inflammatory cytokines, free radicals and NO. In addition, propofol abrogates the microvascular leakage of water and protein in the lungs. The results imply that the Use of propofol in critically ill is not only for sedation, but also Useful for the prevention of inflammatory progression and lung damage. (c) 2006 Elsevier Ltd. All rights reserved.
引用
收藏
页码:503 / 512
页数:10
相关论文
共 36 条
[1]
THE WIDELY USED ANESTHETIC AGENT PROPOFOL CAN REPLACE ALPHA-TOCOPHEROL AS AN ANTIOXIDANT [J].
AARTS, L ;
VANDERHEE, R ;
DEKKER, I ;
DEJONG, J ;
LANGEMEIJER, H ;
BAST, A .
FEBS LETTERS, 1995, 357 (01) :83-85
[2]
COMPARISON OF PROPOFOL AND MIDAZOLAM FOR SEDATION IN CRITICALLY ILL PATIENTS [J].
AITKENHEAD, AR ;
WILLATTS, SM ;
PARK, GR ;
COLLINS, CH ;
LEDINGHAM, IM ;
PEPPERMAN, ML ;
COATES, PD ;
BODENHAM, AR ;
SMITH, MB ;
WALLACE, PGM .
LANCET, 1989, 2 (8665) :704-709
[3]
Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care [J].
Angus, DC ;
Linde-Zwirble, WT ;
Lidicker, J ;
Clermont, G ;
Carcillo, J ;
Pinsky, MR .
CRITICAL CARE MEDICINE, 2001, 29 (07) :1303-1310
[4]
MEASUREMENT OF NITRIC-OXIDE IN BIOLOGICAL MODELS [J].
ARCHER, S .
FASEB JOURNAL, 1993, 7 (02) :349-360
[5]
Pathological aspects of apoptosis in severe sepsis and shock? [J].
Ayala, A ;
Lomas, JL ;
Grutkoski, PS ;
Chung, CS .
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2003, 35 (01) :7-15
[6]
Free radical and drug oxidation products in an intensive care unit sedative: Propofol with sulfite [J].
Baker, MT ;
Gregerson, MS ;
Martin, SM ;
Buettner, GR .
CRITICAL CARE MEDICINE, 2003, 31 (03) :787-792
[7]
Sepsis: A new hypothesis for pathogenesis of the disease process [J].
Bone, RC ;
Grodzin, CJ ;
Balk, RA .
CHEST, 1997, 112 (01) :235-243
[8]
BRIGHAM KL, 1986, AM REV RESPIR DIS, V133, P913
[9]
PROPOFOL - AN UPDATE OF ITS USE IN ANESTHESIA AND CONSCIOUS SEDATION [J].
BRYSON, HM ;
FULTON, BR ;
FAULDS, D .
DRUGS, 1995, 50 (03) :513-559
[10]
PULMONARY CAPILLARY-PRESSURE - A REVIEW [J].
COPE, DK ;
GRIMBERT, F ;
DOWNEY, JM ;
TAYLOR, AE .
CRITICAL CARE MEDICINE, 1992, 20 (07) :1043-1056