左旋精氨酸对急性心肌缺血／再灌注损伤大鼠内皮素-1的影响  

L-arginine suppresses ischemia/reperfusion induced up-regulation of endothelin-1 production in a rat model of acute myocardial injury

作　　者：董化江[1,4] 单娜娜[2] 罗悦晨[3] 高富合[1,4] 李雪[1,4] 徐健[1,4] 徐鹏霄[1,4] 杨德慧[1,4] 李伯森[1,4] 单云官[1,4] 

机构地区：[1]武警后勤学院解剖学教研室,天津300162 [2]武警后勤学院教育技术中心,天津300162 [3]天津医科大学 [4]民政部101研究所遗体防腐整容重点实验室

出　　处：《中国危重病急救医学》2011年第12期731-733,共3页Chinese Critical Care Medicine

基　　金：国家“十一五”科技支撑计划项目（2007BAK38805）

摘　　要：目的探讨内皮素-1（ET-1）在大鼠心肌缺血／再灌注（I／R）损伤过程中的变化规律及左旋精氨酸（L—Arg）的影响。方法采用结扎冠状动脉前降支0．5h复制Wistar大鼠心肌I／R损伤模型。110只大鼠按随机数字表法分为假手术组（C）、缺血0．5h组（I）、缺血0．5h＋再灌注0．5h组（R0．5）、缺血0．5h＋再灌注1h组（R1）、缺血0．5h＋再灌注2h组（R2）、L—Arg＋假手术组（L＋C）、L—Arg＋缺血0．5h组（L＋I）、L—Arg＋缺血0．5h＋再灌注0．5h组（L＋R0．5）、L—Arg＋缺血0．5h＋再灌注1h组（L＋R1）、L—Arg＋缺血0．5h＋再灌注2h组（L＋R2）。用酶联免疫吸附法测定各组大鼠血清肌酸激酶（CK）、乳酸脱氢酶（LDH）活性；用放射免疫法测量血清ET-1水平；用逆转录-聚合酶链反应（RT—PCR）、蛋白质免疫印迹法（Westernblotting）检测各组心肌组织中ET-1mRNA和蛋白表达。结果I组和R组血清CK、LDH、ET-1均较C组明显升高，且R组较I组升高明显。R组ET-1mRNA和蛋白表达均较C组明显升高，以R2组最为显著（ET-1mRNA：0．775±0．029比0．310±0．076；ET-1蛋白：0．773±0．055比0．340±0．099，均P〈0．05）；而静脉给予L—Arg预处理可明显降低ET-1mRNA和蛋白表达（ET-1mRNA：0．340±0．049比0．775±0．029IET-1蛋白：0．390±0．094比0．773±0．055，均P〈O．05）。结论在心肌I／R损伤的某些阶段可试用L—Arg进行干预，降低ET-1的表达。Objective To examine the level of endothelin-1 （ET-1） in serum and its expression in myocardium tissue during the development of acute myocardial ischemia/reperfusion （I/R） injury in rat and the effects of L-arginine （L-Arg） administration on these indexes. Methods One hundred and ten Wistar rats were randomly divided into nine groups to receive： （1） sham surgery, （2）isehemia （1, by ligation of anterior descending coronary artery for 30 minutes）, （3） I＋reperfusion （R, by the removal of the ligature） for 0.5 hour, （4） I＋R for 1 hour, （5） Iq-R for 2 hours; group （6）-（9） also received I/R treatment as in group 2-5 respectively but with L-Arg pretreatment. Blood and myocardium tissue samples were collected by the end of the experiment for the analysis of ： serum level of creatine kinase （CK）, lactate dehydrogenase [LDH, by enzyme linked immunosorbent assay （ELISA）], ET-1 （radioimmunoassay）, and the tissue content of ET-1 mRNA/peptide [by reverse-transcription polymerase chain-reaction （RT-PCR） and Western blotting3. Results In comparison with the sham treated control animals, the serum levels of CK, LDH, and ET-1 were all significantly higher in the groups treated with I/R （particularly those exposed to reperfusion）. The myocardial tissue content of ET-1 mRNA/peptide were also significantly increased in I/R treated groups （particularly the I＋R 2 hours group） as compared to control （ET-1 mRNA：0. 775±0. 029 vs. 0. 310±0.076; ET-1 peptide： 0. 773±0. 055 vs. 0. 340±0. 099, both P〈0.05）. The i.v. administration of L-Arg significantly suppressed the up-regulation of tissue content of ET-1 mRNA /peptide in I/R treated animals （ET-1 mRNA： 0.340±0.049 vs. 0.7754-0.029; ET-1 peptide： 0.390±0.094 vs. 0.773±0.055, both P〈0.05）. Conclusion L-Arg may be tested during certain stage of I/R injury as a therapeutic intervention for the suppression of ET-1 up-regulation.

关 键 词：大鼠 缺血/再灌注损伤 心肌 内皮素一1 左旋精氨酸 

分 类 号：R542.22[医药卫生—心血管疾病]