Ulinastatin suppresses inflammatory response in acute lung injury induced by lipopolysacccharide_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

 LIU Hong ¹ , AN Youzhong ² , LI Fangfang ¹ , GUO Yan ¹

Intensive Care Unit ， The First Hospital of Shanxi Medical University.Taiyuan ， Shanxi ， 030001 ， China Corresponding author ： LIU Hong ， E-mail ： LH9098@yahoo.com.cn;

Corresponding author：

LIU Hong, Email: LH9098@yahoo.com.cn

Keywords：

Acute lung injury; Ulinastatin; Interleukin 18; Nuclear factor κB

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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: Copy

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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.
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．.

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．.

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Chinese Journal of Respiratory and Critical Care Medicine

Ulinastatin suppresses inflammatory response in acute lung injury induced by lipopolysacccharide

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