摘要
目的探讨p38丝裂原活化蛋白激酶(p38MAPK)在肠缺血再灌注损伤大鼠炎性反应中的作用。方法健康成年雄性Wistar大鼠30只,随机分为3组(n=10):假手术组(S组)、缺血再灌注组(I/R组)和p38MAPK抑制剂SB203580组(SB组)。采用夹闭肠系膜上动脉(SMA)的方法制备肠缺血再灌注损伤模型。I/R组和SB组夹闭SMA 1 h再灌注6 h,SB组缺血前30 min经股静脉注射p38MAPK特异性抑制剂SB203580 100μg/kg。于再灌注6 h时,处死大鼠,测定血浆肿瘤坏死因子-α(TNF-α)浓度、双胺氧化酶(DAO)活性及小肠组织TNF-α含量、p38MAPK、细胞间粘附分子-1(ICAM-1)表达水平,在光镜下观察小肠组织病理学,并进行小肠组织损伤程度评分。结果与S组比较,I/R组血浆TNF-α浓度、DAO活性及小肠组织p38MAPK、ICAM-1表达、TNF-α含量、小肠组织损伤程度评分升高,SB组血浆DAO活性、小肠组织ICAM-1表达、TNF-α含量及小肠组织损伤程度评分升高(P〈0.05);与I/R组比较,SB组血浆TNF-α浓度、DAO活性及小肠组织p38MAPK、ICAM-1表达和TNF-α含量、小肠组织损伤程度评分降低(P〈0.05)。结论p38MAPK参与了肠缺血再灌注损伤大鼠炎性反应。
Objective To investigate the role of p38 mitogenoactivated protein kinase (p38MAPK) in inflammatory response to intestinal ischemia-reperfusion (I/R) injury. Methods Thirty adult male Wistar rats weighing 200-250 g were randomly divided into 3 groups ( n = 10 each) : Ⅰ control group (C) ; Ⅱ I/R group and Ⅲ SB203580 + I/R (SB). The animals were anesthetized with intraperitoneal 7% chloral hydrate 350 mg/kg. Intestinal I/R was produced by occluding superior mesenteric artery for 1 h followed by 6 h reperfusion in group Ⅱand Ⅲ . In group Ⅲ SB203580 ( a selective p38MAPK inhibitor) 100μg/kg was given intravenously 30 min before ischemia. Blood samples were collected at the end of 6 h reperfusion for determination of plasma TNF-α concentration and diaminoxidase (DAO) activity. A small segment of ileum was obtained for determination of TNF-α content and expression of p38MAPK and ICAM-1 protein and microscopic examination. Results The extent of damage to small intestine was significantly greater in group I/R and SB than in group C. The plasma DAO activity and TNF-α concentration and the expression of p38MAPK and ICAM-1 protein and TNF-α content in small intestine tissue were significantly increased in group I/R and SB as compared to control group. SB203580 pretreatment significantly attenuated the I/R-induced deleterious changes. Conclusion p38MAPK is involved in the inflammatory response to intestinal I/R injury in rats.
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2007年第9期839-841,共3页
Chinese Journal of Anesthesiology
关键词
P38丝裂原活化蛋白激酶类
再灌注损伤
肠
炎症
p38 Mitogen-activated protein kinases
Reperfusion injury
Intestines
Inflammation