血红素加氧酶-1基因转染对大鼠心肌缺血再灌注损伤的保护作用  

Protective effects of heme oxygenase-1 gene transfection on myocardial ischemia-reperfusion injury in rats

作　　者：姜大春[1] 何国祥[1] 刘志涛[1] 刘建平[1] 唐兵[2] 李德[2] 

机构地区：[1]第三军医大学西南医院心内科,重庆400038 [2]成都军区总医院心内科,四川成都610083

出　　处：《西南国防医药》2009年第5期492-495,共4页Medical Journal of National Defending Forces in Southwest China

摘　　要：目的:观察腺病毒介导的血红素加氧酶-1基因(rHO-1)转染后,HO-1在大鼠心肌的表达及其对缺血再灌注损伤心肌的保护作用。方法:雄性SD大鼠随机分为4组:假手术对照组(SH)、生理盐水组(NS)、空载体组(Ad)和Ad-HO-1转染组(HO),各组12只。后3组分别于心尖部分别注射1ml生理盐水、含空载体腺病毒(5.0×109PFU)和重组HO-1腺病毒50μl(7.5×109PFU)。在基因转染3d后,采用左冠状动脉前降支结扎开放建立心肌缺血再灌注模型。每组大鼠测定心功能后取心腔内血,做心肌酶检测,处死大鼠并取左心室标本,测定左心室心肌梗死面积,于荧光显微镜下观察心肌组织荧光蛋白的表达情况,RT-PCR、Western blot检测心肌组织HO-1mRNA、蛋白的表达。结果:HO组中HO-1表达量明显高于Ad组和NS组,Ad和HO组左室心肌均见有荧光蛋白表达,其转染率为(55.5±3.5)%。各时相点HO组的SBP、DBP、MAP、+dp/dtmax和-dp/dtmax等指标恢复率均显著高于Ad组和NS组(P<0.01)。与SH组比较,NS组、Ad组血清LDH和CK-MB水平、梗死心肌重量、心肌梗死面积升高(P<0.01)。与NS组或Ad组比较,HO组血清LDH和CK-MB水平、梗死心肌重量、心肌梗死面积减少(P<0.01)。结论:腺病毒携带的HO-1基因能有效的转染心肌组织,并在体内稳定表达;HO-1基因转染对缺血再灌注的心肌有明显的保护作用。Objective .To observe the expression of heine oxygenase - 1 （ HO - 1 ） gene in rat＇s cardiomyoeytes and its protective effects on myocardial ischemia - reperfusion injury after transfcetion of adenovirus - mediated rat＇s HO - 1 gene. Methods：48 male healthy SD rats were randomly divided into four groups （ n = 12 ） ： sham - operated control group （ SH）, normal saline group （ NS）, empty vector group （Ad） and Ad - HO - 1 transfection group （HO）. Rats of NS, Ad and HO groups were injected with 1 ml of normal saline, 1 ml of normal saline containing empty vector adenovirus （5.0 × 10^9 PFU）or 50 μl of recombinant HO - 1 adenovirus （7.5 × 10^9 PFU）through the cardiac apex, respectively. Three days after gene transfection,myocardial ischemia - reperfusion models in these three groups were established by opening the occlusion of the left anterior descending from coronary artery. After determination of cardiac function of rats in each group, intracardiac blood was obtained for myocardial zymograms detection. Rats were sacrificed and left ventricular specimens were taken to measure the infarction area, and expression of fluorescent protein in the myocardial tissue was observed under fluorescence microscope. The expressions of HO - 1 mRNA and protein in myocardial tissue were detected by RT - PCR and Western blot,respectively. Results：Semi - quantitative RT - PCR and Western blot analysis showed that the expressions of HO - 1 mRNA and protein in HO group were significantly higher than those in Ad group and NS group. Fluorescent protein expression was seen in left ventricular myocardium in both Ad group and HO group, and the transfection rate was （ 55, 5 ＋ 3.5 ） %. However, the recovery rate of SBP, DBP,MAP, ＋ dp/dtmax and - dp/dtmax,etc at each time point in HO group were significantly higher than those in Ad group and NS granp（P 〈 0.01 ）. Compared with the SH group,levels of serum LDH and CK - MB, the weight of infarcted myocardium and the myocardial infarction area

关 键 词：血红素氧化酶-1 心肌 再灌注损伤 转染 腺病毒 

分 类 号：R542.2[医药卫生—心血管疾病]