Objective
To investigate the possible role of ulinastatin(UTI) in f lipopolysacccharide (LPS)-induced acute lung injury(ALI).Methods Thirty male SD rats were randomly divided into three groups,ie.a normal control group,a LPS group and a LPS plus UTI group.The rats were injected with 1 mL of normal saline via caudal vein in the control group,with LPS 5 mg/kg via caudal vein in the LPS group,and with UTI 100000 U/kg shortly after injection with LPS in the LPS plus UTI group.The rats were sacrificed 4 h after the injection.Lung wet/dry weight ratio was measured.IL-18 level in serum and lung tissue was determined by ELISA and the expression of NF-κB in lung tissue was determined by immunohistochemistry.Pathological changes of rats’ lung were observed by optical and electron microscope.Results Compared with the control group,IL-18 level in serum and NF-κB expression in lung tissue were significantly higher in the LPS group(P lt;0.01).The IL-8 level was somewhat elevated in the LPS+UTI group but with no significant difference from that in control group was found (P gt;0.05).The lung inflammation in the LPS+UTI group was milder than that in the LPS rats.Conclusion UTI can alleviate LPS-induced inflammatory reaction and lung injury in rat model.
Citation:
LIU Hong,AN Youzhong,LI Fangfang,GUO Yan. Ulinastatin suppresses inflammatory response in acute lung injury induced by lipopolysacccharide. Chinese Journal of Respiratory and Critical Care Medicine, 2008, 08(4): 290-293. doi:
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叶任高,陆再英,主编.内科学.第6版.北京:人民卫生出版社,2005,143-147.
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Downey GP,Dong Q,Kruger J,et al.Regulation of neutrophil activation in acute lung injury.Chest,1999,116(Suppl 1):S46-S54.
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简文,尹文,戚好文,等.山莨菪碱干预急性肺损伤家兔肺泡巨噬细胞中核因子κB和肿瘤坏死因子α mRNA的表达.中国临床康复,2006,10:94-96.
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大西冶夫,小雀浩司,延原正弘.蛋白酶抑制剂--乌司他丁的药理作用.应用药理(E1),1986,31:663-675.
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Okuhama Y,Shiraishi M,Higa T.Protective effects of ulinastatin against ischemia-reperfusion injury.J Surg Res,1999,82:34-42.
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Aosasa S,Ono S,Mochizuki H,et al.Mechanism of the inhibitory effect of protease inhibitor on tumor necrosis factor alpha production of monocytes.Shock,2001,15:101-105.
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Silliman CC,Voelkel NF,Allard JD,et al.Plasma and lipids from stored packed red blood cells cause acute lung injury in an animal model.J.Clin.Invest,1998,101:1458-1467.
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孙来芳,潘利伟.乌司他丁影响严重脓毒症大鼠IL-10、TNF-α、IL-1β水平的研究.临床外科杂志,2005,13:770-772.
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9. |
Coimbra R,Melbostad H,Loomis W,et al.LPS-induced acute lung injury is attenuated by phosphodiesterase inhibition:effects on proinflammatory mediators,metalloproteinases,NF-kappaB,and ICAM-1 expression.J Trauma,2006,60:115-125.
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10. |
Smith KM,Mrozek JD,Simonton SC,et a1.Prolonged partial liquid ventilation using conventional and high-frequency ventilatory techniques:gas exchange and lung pathology in an animal model of respiratory distress syndrome..Crit Care Med,1997,25:1888-1897.
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11. |
陈灏珠,主编.实用内科学.第12版.北京:人民卫生出版社,2005,1794-1795.
|
12. |
蒋定文,李楚芳.IL-18与IL-l相似的信号转导途径.国外医学免疫学分册,2000,23:185-187.
|
13. |
Rau B,Baumgart K,Paszkowski AS,et al.Clinical relevance of caspase-1 activated cytokines in acute pancreatitis:high correlation of serum interleukin-18 with pancreatic necrosis and systemic complications.Crit Care Med,2001,29:1556-1562.
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14. |
陈晓星,黄霞玥,刘平,等.乌司他丁治疗急性胰腺炎的临床总结.中华肝胆外科杂志,2002,8:186-187.
|
15. |
杨凯,沈锦松,章强松.乌司他丁治疗创伤后急性肺损伤40例临床观察.中国急救医学,2006,26:229-230..
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- 1. 叶任高,陆再英,主编.内科学.第6版.北京:人民卫生出版社,2005,143-147.
- 2. Downey GP,Dong Q,Kruger J,et al.Regulation of neutrophil activation in acute lung injury.Chest,1999,116(Suppl 1):S46-S54.
- 3. 简文,尹文,戚好文,等.山莨菪碱干预急性肺损伤家兔肺泡巨噬细胞中核因子κB和肿瘤坏死因子α mRNA的表达.中国临床康复,2006,10:94-96.
- 4. 大西冶夫,小雀浩司,延原正弘.蛋白酶抑制剂--乌司他丁的药理作用.应用药理(E1),1986,31:663-675.
- 5. Okuhama Y,Shiraishi M,Higa T.Protective effects of ulinastatin against ischemia-reperfusion injury.J Surg Res,1999,82:34-42.
- 6. Aosasa S,Ono S,Mochizuki H,et al.Mechanism of the inhibitory effect of protease inhibitor on tumor necrosis factor alpha production of monocytes.Shock,2001,15:101-105.
- 7. Silliman CC,Voelkel NF,Allard JD,et al.Plasma and lipids from stored packed red blood cells cause acute lung injury in an animal model.J.Clin.Invest,1998,101:1458-1467.
- 8. 孙来芳,潘利伟.乌司他丁影响严重脓毒症大鼠IL-10、TNF-α、IL-1β水平的研究.临床外科杂志,2005,13:770-772.
- 9. Coimbra R,Melbostad H,Loomis W,et al.LPS-induced acute lung injury is attenuated by phosphodiesterase inhibition:effects on proinflammatory mediators,metalloproteinases,NF-kappaB,and ICAM-1 expression.J Trauma,2006,60:115-125.
- 10. Smith KM,Mrozek JD,Simonton SC,et a1.Prolonged partial liquid ventilation using conventional and high-frequency ventilatory techniques:gas exchange and lung pathology in an animal model of respiratory distress syndrome..Crit Care Med,1997,25:1888-1897.
- 11. 陈灏珠,主编.实用内科学.第12版.北京:人民卫生出版社,2005,1794-1795.
- 12. 蒋定文,李楚芳.IL-18与IL-l相似的信号转导途径.国外医学免疫学分册,2000,23:185-187.
- 13. Rau B,Baumgart K,Paszkowski AS,et al.Clinical relevance of caspase-1 activated cytokines in acute pancreatitis:high correlation of serum interleukin-18 with pancreatic necrosis and systemic complications.Crit Care Med,2001,29:1556-1562.
- 14. 陈晓星,黄霞玥,刘平,等.乌司他丁治疗急性胰腺炎的临床总结.中华肝胆外科杂志,2002,8:186-187.
- 15. 杨凯,沈锦松,章强松.乌司他丁治疗创伤后急性肺损伤40例临床观察.中国急救医学,2006,26:229-230..