抗细胞间黏附分子1靶向液态氟碳微球对大鼠缺血再灌注损伤心肌的靶向结合和抗炎作用的研究  

TARGETED COMBINATION AND ANTI-INFLAMMATORY EFFECTS OF ANTI-INTERCELLULAR ADHESION MOLECULE 1 TARGETED PERFLUOROOCTYLBROMIDE PARTICLES ON MYOCARDIAL ISCHEMIAREPERFUSION INJURY IN RAT MODEL

作　　者：尚艳文[1] 唐红[1] 韦馨[1] 侯江龙[2] 王炼[3] 李国华[4] 宋海波[4] 方华[4] 

机构地区：[1]四川大学华西医院心内科,成都610041 [2]四川大学华西医院胸心外科,成都610041 [3]四川大学华西口腔医院病理科 [4]四川大学华西医院麻醉科,成都610041

出　　处：《中国修复重建外科杂志》2013年第3期340-344,共5页Chinese Journal of Reparative and Reconstructive Surgery

基　　金：国家自然科学基金面上项目(30872535);四川省科技支撑资助项目(2008SZ0198)~~

摘　　要：目的探讨抗细胞间黏附分子1(intercellular adhesion molecule 1,ICAM-1)靶向液态氟碳(per-fluorooctylbromide,PFOB)微球对大鼠缺血再灌注损伤心肌的靶向结合和抗炎作用。方法取成年SD大鼠76只,雌雄不限,体重250～300 g。取30只采用结扎冠状动脉左前降支30 min方法制备心肌缺血再灌注损伤模型,免疫组织化学染色观察缺血再灌注6 h心肌细胞表面ICAM-1蛋白表达情况,以10只正常大鼠作为对照;液相芯片技术检测缺血再灌注6、12、18、24、30、36、42、48 h血清中IL-8含量。另取36只大鼠随机分为6组(n=6):心肌缺血再灌注/靶向PFOB微球组(A组)、心肌缺血再灌注/普通PFOB微球组(B组)、正常大鼠/靶向PFOB微球组(C组)、正常大鼠/普通PFOB微球组(D组)、心肌缺血再灌注/生理盐水组(E组)、假手术组(F组)。A、B、E组大鼠同法建立心肌缺血再灌注损伤模型;F组开胸后在冠状动脉下穿线但不结扎。缺血再灌注6 h后,A、B、C、D组经颈静脉注入1 mL对应的PFOB微球,E组注入1 mL生理盐水。超声观察A、B、C、D组注入PFOB微球前后心肌显像情况;荧光显微镜观察A、B、C、D组心脏冰冻切片微球结合情况;液相芯片技术检测A、B、E、F组缺血再灌注6 h及24 h血清中IL-8含量。结果缺血再灌注6 h后大鼠心肌细胞表面ICAM-1蛋白表达以前间隔和左室前壁较明显;IL-8含量自缺血再灌注6 h起开始增高,24 h达峰值。注入PFOB微球后至缺血再灌注24 h A、B、C、D组超声观察均未见明确受损心肌靶向显影;荧光显微镜下A组前间隔和左室前壁心肌细胞核周围可见绿染的靶向PFOB微球,B、C、D组均未见绿色荧光。缺血再灌注6 h,A、B、E组间IL-8含量相似(P>0.05),但均高于F组(P<0.05);24 h时A、B组间IL-8含量相似(P>0.05),均低于E组(P<0.05)。结论抗ICAM-1靶向PFOB微球可靶向结合大鼠缺血再灌注损伤心肌,通过其抗炎作用保护受损心肌。Objective To investigate the targeted combination and anti-inflammatory effects of anti-intercellular adhesion molecule 1 （ICAM-1） targeted perfluorooctylbromide （PFOB） particles on myocardial ischemia-reperfusion injury in rat model. Methods Seventy-six adult Sprague Dawley rats （male or female, weighing 250-300 g） were selected for experiment. The models of myocardial ischemia-reperfusion injury were established by l igating the left anterior descending coronary artery for 30 minutes in 30 rats. The expression of ICAM-1 protein was detected by immunohistochemistry staining at 6 hours after reperfusion, and the normal myocardium of 10 rats were harvested as control; then the content of interleukin 8 （IL-8） in serum was tested every 6 hours from 6 hours to 48 hours after reperfusion. The other 36 rats were randomly divided into 6 groups （n=6）： ischemia-reperfusion injury model/targeted PFOB particles group （group A）, ischemia-reperfusion injury model/untargeted PFOB group （group B）, normal control/targeted PFOB particles group （group C）, normal control/untargeted PFOB particles group （group D）, ischemia-reperfusion injury model/normal saline group （group E）, and sham operation group （group F）. The ischemia-reperfusion injury models were established in groups A, B, and E; while a thread crossed under the coronary artery, which was not ligated after open-chest in group F. After 6 hours of reperfusion, 1 mL of corresponding PFOB particles was injected through juglar vein in groups A, B, C, and D, while 1 mL of nomal saline was injected in group E. Ultrasonography was performed in groups A, B, C, and D before and after injection. The targeted combination was tested byfluorescence microscope. The content of IL-8 was tested after 6 and 24 hours of reperfusion by liquid chip technology in groups A, B, E, and F. Results After 6 hours of reperfusion, the expression of ICAM- 1 protein significantly increased in the anterior septum and left ventricular anterior waU of the rat mo

关 键 词：心肌缺血再灌注损伤 液态氟碳 细胞间黏附分子1 大鼠 

分 类 号：R541[医药卫生—心血管疾病]