目的 探討蛋白酶抑制劑烏司他丁對(duì)內(nèi)毒素(LPS)誘導(dǎo)的大鼠ALI的保護(hù)作用。方法 將30只SD雄性大鼠區(qū)組隨機(jī)分為三組:正常對(duì)照組、LPS組和UTI組。LPS組經(jīng)尾經(jīng)脈注射LPS造成大鼠ALI模型,UTI組在按與LPS組相同標(biāo)準(zhǔn)給LPS的同時(shí)給予烏司他?。║TI)(10萬U/kg體重)。4 h后取肺組織測(cè)量肺濕干重比(W/D),ELISA法檢測(cè)動(dòng)脈血及肺組織中白細(xì)胞介素-18(IL-18)水平,免疫組化法檢測(cè)肺組織中核因子κB(NF-κB)的表達(dá),光鏡和電鏡下觀察肺組織病理變化。結(jié)果 比較肺組織濕干重比、血清及肺組織中IL-18的水平和肺組織NF-κB表達(dá),LPS組高于對(duì)照組;UTI組高于對(duì)照組但低于LPS組。LPS組肺泡間質(zhì)充血水腫、炎性細(xì)胞浸潤明顯;UTI組上述現(xiàn)象較輕。LPS組肺巨噬細(xì)胞線粒體、內(nèi)質(zhì)網(wǎng)腫脹明顯;UTI組肺巨噬細(xì)胞內(nèi)質(zhì)網(wǎng)僅有零散現(xiàn)象,無腫脹。結(jié)論 烏司他丁可通過降低炎性細(xì)胞因子IL-18和NF-κB的表達(dá)減輕LPS所致ALI的肺部炎性反應(yīng)。
引用本文: 劉虹 ,安友仲,李芳芳,郭焱. 烏司他丁對(duì)脂多糖誘導(dǎo)大鼠急性肺損傷作用的研究. 中國呼吸與危重監(jiān)護(hù)雜志, 2008, 08(4): 290-293. doi: 復(fù)制
1. | 葉任高,陸再英,主編.內(nèi)科學(xué).第6版.北京:人民衛(wèi)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. | 簡文,尹文,戚好文,等.山莨菪堿干預(yù)急性肺損傷家兔肺泡巨噬細(xì)胞中核因子κB和腫瘤壞死因子α mRNA的表達(dá).中國臨床康復(fù),2006,10:94-96. |
4. | 大西冶夫,小雀浩司,延原正弘.蛋白酶抑制劑--烏司他丁的藥理作用.應(yīng)用藥理(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. | 孫來芳,潘利偉.烏司他丁影響嚴(yán)重膿毒癥大鼠IL-10、TNF-α、IL-1β水平的研究.臨床外科雜志,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. | 陳灝珠,主編.實(shí)用內(nèi)科學(xué).第12版.北京:人民衛(wèi)生出版社,2005,1794-1795. |
12. | 蔣定文,李楚芳.IL-18與IL-l相似的信號(hào)轉(zhuǎn)導(dǎo)途徑.國外醫(yī)學(xué)免疫學(xué)分冊(cè),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. | 陳曉星,黃霞玥,劉平,等.烏司他丁治療急性胰腺炎的臨床總結(jié).中華肝膽外科雜志,2002,8:186-187. |
15. | 楊凱,沈錦松,章強(qiáng)松.烏司他丁治療創(chuàng)傷后急性肺損傷40例臨床觀察.中國急救醫(yī)學(xué),2006,26:229-230.. |
- 1. 葉任高,陸再英,主編.內(nèi)科學(xué).第6版.北京:人民衛(wèi)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. 簡文,尹文,戚好文,等.山莨菪堿干預(yù)急性肺損傷家兔肺泡巨噬細(xì)胞中核因子κB和腫瘤壞死因子α mRNA的表達(dá).中國臨床康復(fù),2006,10:94-96.
- 4. 大西冶夫,小雀浩司,延原正弘.蛋白酶抑制劑--烏司他丁的藥理作用.應(yīng)用藥理(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. 孫來芳,潘利偉.烏司他丁影響嚴(yán)重膿毒癥大鼠IL-10、TNF-α、IL-1β水平的研究.臨床外科雜志,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. 陳灝珠,主編.實(shí)用內(nèi)科學(xué).第12版.北京:人民衛(wèi)生出版社,2005,1794-1795.
- 12. 蔣定文,李楚芳.IL-18與IL-l相似的信號(hào)轉(zhuǎn)導(dǎo)途徑.國外醫(yī)學(xué)免疫學(xué)分冊(cè),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. 陳曉星,黃霞玥,劉平,等.烏司他丁治療急性胰腺炎的臨床總結(jié).中華肝膽外科雜志,2002,8:186-187.
- 15. 楊凱,沈錦松,章強(qiáng)松.烏司他丁治療創(chuàng)傷后急性肺損傷40例臨床觀察.中國急救醫(yī)學(xué),2006,26:229-230..