PEP-1-CAT融合蛋白预处理对在体大鼠心肌缺血/再灌注损伤的保护作用  

The Protective Effect of PEP-1-CAT Fusion Protein Preconditioning on Myocardial Ischemia-reperfusion Injury in Rats in Vivo

作　　者：张永军[1,2] 王家宁[1] 唐俊明[1] 黄永章[1] 杨建业[1] 郭凌郧[1] 孔霞[1] 郑飞[1] 

机构地区：[1]湖北医药学院附属人民医院临床医学研究所,湖北十堰442000 [2]湖北医药学院附属人民医院心内科,湖北十堰442000

出　　处：《郧阳医学院学报》2010年第4期303-307,298,共6页Journal of Yunyang Medical College

基　　金：湖北省高等学校优秀中青年科技创新团队(T200811)

摘　　要：目的:研究PEP-1-CAT融合蛋白预处理对在体大鼠心肌缺血/再灌注损伤的保护作用,探讨其可能的作用机制。方法:60只SD大鼠随机分为5组:假手术组(Sham组)、缺血/再灌注组(I/R组)、低剂量预处理组(I/R+100μgPEP-1-CAT)、中剂量预处理组(I/R+300μgPEP-1-CAT)、高剂量预处理组(I/R+500μgPEP-1-CAT)。假手术组和缺血/再灌注组预先注射1mL的0.9%氯化钠溶液,低中高剂量预处理组分别注射100、300、500μg的PEP-1-CAT融合蛋白,7h后结扎冠状动脉前降支1h,再灌注2h后,检测心肌组织中的丙二醛(MDA)和血液中乳酸脱氢酶(LDH)及肌酸激酶(CK)含量,TTC染色测定心肌梗死面积,一步法TUNEL测定凋亡率,免疫荧光测定凋亡蛋白Bax和Bcl-2的表达。结果:与I/R组相比,低中高剂量预处理组显著减少心肌梗死面积(P<0.05或P<0.01),减少MDA的形成(P<0.01)和LDH、CK的释放,使凋亡率下降(P<0.01),下调Bax的表达,上调Bcl-2的表达,使Bax/Bcl-2比值下降。结论:PEP-1-CAT融合蛋白预处理能够明显减少心肌缺血/再灌注损伤,其机制可能与PEP-1-CAT融合蛋白具有抗氧化、抗凋亡作用有关。Objective To investigate the protective effect of PEP-1-CAT fusion protein on ischemia-reperfusion injury in rats in vivo and to explore its potential mechanism.Methods Sixty SD rats were divided into 5 groups at random,Sham-operated group(sham group)and ischemia-reperfusion group(I/R group)were pretreated with 1 mL NS injection,three PEP-1-CAT pretreated groups were administered with 100 μg,300 μg and 500 μg PEP-1-CAT via caudal vein,respectively.Then the left main coronary artery was occluded for 1 h followed by a 2 h reperfusion at 7 h after administration.The infarct size were measured by TTC staining,the contents of MDA in myocardium and LDH,CK in serum were determined.The myocardial cell apoptosis was determined with TUNEL method,the expression changes of Bcl-2 and Bax in myocardium of left ventricle were detected with immunofluorescent method.Results Compared with I/R group,the myocardial infarct size,the content of MDA,the release of LDH and CK,the apoptosis were all significantly decreased(P<0.05 or P<0.01),the expression of Bcl-2 was down regulated,the expression of Bax was up regulated,the ratio of Bax/Bcl-2 was correspondingly decreased in all three PEP-1-CAT pretreated groups.Conclusion PEP-1-CAT fusion protein preconditioning could obviously decrease ischemia-reperfusion injury,which may be related to its anti-oxidant and anti-apoptosis effects.

关 键 词：PEP-1 过氧化氢酶 缺血/再灌注损伤 氧自由基 心肌梗死 凋亡 BAX Bcl-2 

分 类 号：R541[医药卫生—心血管疾病]