免疫受损大鼠铜绿假单胞菌肺部感染VE-cadherin的变化及其意义  

The study on the change and its significance of VE-cadherin in pulmonary infection with Pseudomonas aeruginosa in immunocompromised rats

作　　者：潘珏[1] 何礼贤[1] 瞿介明[1] 刘银坤[2] 陈雪华[1] 姜红妮[1] 李倬哲[1] 

机构地区：[1]复旦大学附属中山医院肺科复旦大学呼吸病研究所,上海200032 [2]复旦大学肝癌研究所

出　　处：《中国呼吸与危重监护杂志》2003年第5期303-306,共4页Chinese Journal of Respiratory and Critical Care Medicine

基　　金：上海市卫生系统优秀学科梯队带头人培养计划 (BR0 30 );教育部骨干教师计划资助

摘　　要：目的　通过建立免疫受损 (ICH)铜绿假单胞菌 (PA)肺炎大鼠模型 (ICH组 ) ,并与正常大鼠PA肺炎 (对照组 )比较 ,检测肺血管内皮钙粘蛋白 (VE cadherin)的动态表达 ,以明确VE cadherin是否参与ICH肺部PA感染肺微血管损伤机制及其意义。方法　用环磷酰胺 (15mg·kg- 1·d- 1)联合醋酸可的松 (10 0mg·kg- 1·d- 1)建立ICH大鼠模型 ,通过气管内注入PA溶液 (0 2mlATCC2 78536× 10 8CFU/ml)复制肺部PA感染模型。采用免疫点印迹方法测定血清、支气管肺泡灌洗液 (BALF)中VE cadherin的含量 ,免疫组化 (二步法 )测定肺组织VE cadherin的表达。结果　两组血清VE cadherin的表达在各个时间点差异较少 ,表达稳定 ,两组对比无明显差异 (P >0 0 5)。灌洗液中VE cadherin的含量时序分析显示 ,感染前两组均有一定量的表达 ;感染后均出现下降 ,ICH组感染后3h和 6h最为明显 (P <0 0 5) ,感染后 9h呈上升趋势 ;对照组在感染后 6h出现最低点 ,各时间点表达与感染前无明显差别。肺组织的VE cadherin在感染前两组肺组织中均有少量表达 ;ICH组在PA感染 6h后呈下降趋势 ,感染PA后各时间点的VE cadherin阳性细胞数与感染前相比 ,无统计学意义(P >0 0 5) ;正常对照组PA感染后VE cadherin阳性细胞数呈增多趋势 。Objective To compare the Pseudomonas aeruginosa (PA) initiated pulmonary infection and kinetics of VE cadherin expression between immunocompromised rats and normal rats, in order to clarify whether the VE cadherin participate in the microvascular injury of pulmonary PA infection in ICH Methods ICH models of rats were established by daily intraperitoneal injection of cyclophophamide (15 mg·kg -1 ·d -1 ) plus subcutaneous injection of cortisone acetate (100 mg·kg -1 ·d -1 ) for 7 consecutive days Rats were intratracheally challenged with Pseudomonas aeruginosa(0 2 ml ATCC 27853 6×10 8CFU/ml) The protein concentrations of VE cadherin in plasma and BALF were measured by immunoblotting Two step procedure of immunohistochemistry was used for VE cadherin in lung tissue Results VE cadherin levels in plasma of two groups were steady at various time points( P >0 05) The contents of VE cadherin in BALF in both group were decreased after infection which were significantly lower at 3 and 6 h(P<0 05) in ICH group The variation of VE cadherin at each time point in control group was slight(P>0 05) The lowest point was at 6 h postinfection In lung tissue,the expression of VE cadherin in ICH group was lower at 6 h postinfection There was no significant difference at each time point In control group,the positive stain appeared gradually stronger at 9 h postinfection and was more obvious than that in ICH group(P<0 05) Conclusions Our results indicate an earlier and long lasting decline of VE cadherin along with severer injury of endothelial cells and higher permeability of pulmonary microvascular in pulmonary infection with PA in ICH,which suggest that VE cadherin may be a alternative mechanism of PA initiated lung injury in ICH other than PMN However,the serum level of VE cadherin may not be regarded as an early marker of PA initiated pulmonary microvascular injury in ICH

关 键 词：免疫受损宿主 ICH 铜绿假单胞菌 PA 血管内皮细胞钙粘蛋白 肺损伤 肺部感染 大鼠模型 动物实验 并发症 

分 类 号：R563.1[医药卫生—呼吸系统]