大鼠肢体缺血再灌注致心肌损伤中过氧化物酶及肿瘤坏死因子-α的动态变化及意义  

Changes of systemic and local myeloperoxidase and tumor necrosis factor-αin rats with myocardial injury induced by hind-limb ischemia-reperfusion

作　　者：陈雯[1] 刘宁[1] 齐迎春[1] 张颖[1] 邓昭阳[1] 杨靖[1] 谢晓华[1] 

机构地区：[1]解放军总医院南楼综合外一科,北京100853

出　　处：《南方医科大学学报》2013年第5期761-764,共4页Journal of Southern Medical University

基　　金：军队"十一五"科技攻关课题(06G117);军队十二五重点科研课题(BWS12J051)

摘　　要：目的研究血浆及心肌局部炎细胞髓过氧化物酶(MPO)及炎性细胞因子肿瘤坏死因子-α(TNF-α)在大鼠肢体缺血再灌注后心血管系统损害中的动态变化及意义。方法应用止血带结扎构建大鼠双下肢缺血再灌注模型,按照缺血及再灌注不同时间点随机分为9组:①正常对照组(C);②缺血2、4 h组(I_2,I_4);③缺血4 h再灌注0.5、2、4、6、12、24 h组(R_(0.5),R_2,R_4,R_6,R_(12),R_(24))。观察各组大鼠血浆及心肌MPO、TNF-α水平的变化,以免疫组化法观察心肌组织TNF-α的表达。结果与C组比较,I_2组血浆及心肌MPO、TNF-α即开始明显上升;与I_4组比较,血浆及心肌MPO分别于再灌注R_(0.5)、R_2组明显升高;R_4组血浆TNF-α明显上升,R_(12)组心肌TNF-α明显下降;R_(24)组血浆MPO、TNF-α明显下降(P<0.05)。R_4血浆MPO、TNF-α心肌TNF-α达到峰值;R_6组心肌MPO达到峰值。TNF-α免疫组化提示I_4组大鼠心肌胞浆即可见较多棕色染色颗粒,R_4组浆棕色染色颗粒继续增多,R_(24)组明显减少。结论炎细胞在心肌组织的聚集活化、全身及心肌局部炎性细胞因子的激活是肢体缺血期及再灌注期心肌损伤的重要病理学基础,其中再灌注期心肌损伤与全身性炎性细胞因子激活关系更大。Objective To explore the role of myeloperoxidase （MPO） and tumor necrosis factor-α （TNF-α） in myocardial injury induced by hind-limb ischemia-reperfusion （IR） in rats. Methods Rat models of bilateral hindlimb IR established using a tourniquet were randomized into 9 groups, including a normal control group normal, 2 ischemic groups with hindlimb ischemia for 2 and 4 h, and 6 IR groups with a 4-h ischemia followed by reperfusion for 0.5, 2, 4, 6, 12, and 24 h. The plasma and myocardial levels of MPO and TNF-a in each group were measured, and the myocardial expression of TNF-α was determined with immunohistochemistry. Results Compared with the normal control group, the rats with a 2-h ischemia showed significantly increased levels of MPO and TNF-α in the plasma and myocardium. Compared with those in rats with a 4-h ischemia, the plasma and myocardial MPO levels increased significantly at 0.5 and 2 h of reperfusion, respectively; the plasma TNF-α level increased significantly at 4 h of reperfusion and myocardial TNF-α level decreased obviously at 12 h; plasma levels of MPO and TNF-a both significantly decreased at 24 h. The plasma MPO and TNF-α and myocardial TNF-α reached the peak levels at 4 h of reperfusion, and the peak myocardial MPO level occurred at 6 h. Immunohistochemistry showed that TNF-a positivity moderately increased after hindlimb ischemia, and further increased at 4 h of reperfusion but obviously reduced at 24 h. Conclusion The activation of systemic and local neutrophils and inflammatory cytokines may play an important role in myocardial injury induced by hindlimb IR in rats.

关 键 词：肢体缺血再灌注 心肌损伤 髓过氧化物酶 肿瘤坏死因子-Α 

分 类 号：R363[医药卫生—病理学]