摘要
目的 探讨细胞穿透肽PEP-1介导血红素加氧酶-1（HO-1）对大鼠离体心脏缺血再灌注损伤的影响.方法 雄性SD大鼠,体重220～280g,制备Langendorff离体心脏灌注模型,选取模型制备成功的离体心脏18个,随机分为3组（n=6）：假手术组（S组）、缺血再灌注组（IR组）和PEP-1/HO-1处理＋缺血再灌注组（HO-1组）.IR组K-H液平衡灌注30 min后,采用停灌40 min再灌注50 min的方法制备缺血再灌注模型.HO-1组在停灌前用含50 μmol/L融合蛋白PEP-1/HO-1的K-H液平衡灌注15 min,S组采用K-H液持续灌注120 min.再灌注50 min时,收集冠脉流出液,测定肌酸激酶（CK）和乳酸脱氢酶（LDH）的活性;取心肌组织,采用Western blot法测定HO-1蛋白表达水平,采用硫代巴比妥酸比色法测定MDA含量,黄嘌呤氧化酶法测定SOD活性.结果 HO-1组心肌组织HO-1蛋白表达水平较IR组升高（P＜0.01）.与S组比较,IR组和HO-1组冠脉流出液CK和LDH活性及心肌组织MDA含量升高,心肌组织SOD活性降低（P＜0.01）;与IR组比较,HO-1组冠脉流出液CK和LDH活性及心肌组织MDA含量降低,心肌组织SOD活性升高（P＜0.01）.结论细胞穿透肽PEP-1可将HO-1蛋白成功导入心肌组织,并减轻大鼠心肌缺血再灌注损伤.
Objective To investigate the protective effects of heme oxygenase-1 （HO-1） mediated by cell penetrating peptide PEP-1 on myocardium against ischemia/reperfusion （IR） injury in isolated rat hearts. Methods Healthy male SD rats weighing 220-280 g were anesthetized with intraperitoneal pentobarbital. Their hearts were excised and perfused in a Langendorff apparatus with K-H solution saturated with 95%O2-5% CO2 at 37 ℃. Eighteen isolated rat hearts were randomly divided into 3 groups （ n = 6 each）： Ⅰ group sham operation （group S）;Ⅱ group IR and Ⅲ group PEP-1/HO-1 ＋ IR （group HO-1）. The isolated rat hearts were perfused with an oxygena-ted （95% O2-5% CO2 ） K-H solution at 37 ℃ in a Langendorff apparatus and were subjected to 40 min of global ischemia followed by 50 min of reperfusion after 30 min of stabilization. In group Ⅲ （group HO- 1 ） the isolated hearts were perfused with 50 μmol/L PEP-1/HO-1 for 15 min before ischemia. After 50 min of reperfusion, HO-1expression, MDA content and SOD activity in myocardial tissues were determined. The activities of creatine kinase （CK） and lactic dehydrogenase （LDH） in coronary effluent fluid were measured. Results The HO- 1 expression was significanfly higher in HO-1 group than in group IR. IR induced significant increase in MDA content and decrease in SOD activity in myocardium and CK and LDH activities in coronary effluent in group Ⅱ compared with group S. PEP-1/HO-1 significantly attenuated IR-induced changes. Conciusion HO-1 mediated by PEP-1 has protective effects on myocardium ngainst IR injury in rats.
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2010年第10期1172-1174,共3页
Chinese Journal of Anesthesiology
基金
国家自然科学基金（30872426）
