CAJ | 학술논문

目的探讨缺血预处理对大鼠缺血再灌注心肌低氧诱导因子1α(HIF-1α)和血红素加氧酶1(HO-1)的影响.方法健康雄性SD大鼠48只,体重220～280 g,随机分为4组(n=12):假手术组(S组)、缺血再灌注组(IR组)、缺血预处理+缺血再灌注组(IP组)和缺血预处理+缺血再灌注+HO-1抑制剂组(HI组).采用结扎左冠状动脉前降支30 min再灌注120 min的方法建立心肌缺血再灌注模型.S组仅在冠状动脉下穿线;IP组于缺血前采用结扎/放松左冠状动脉前降支各5 min,重复3次的方法行缺血预处理;HI组于缺血预处理前1 d腹腔注射锌原卟啉Ⅸ 10 ms/ks,其余同IP组.于再灌注结束时测定心肌HIF-1α、HO-1的mRNA和蛋白表达、HO-1活性、SOD活性及MDA含量,计算心肌梗死面积,取动脉血样测定血清TNF-α和IL-6的浓度.结果与S组比较,IR组、IP组和HI组心肌SOD活性降低,MDA含量升高,血清TNF-α和IL-6的浓度升高(P＜0.01);与IR组比较,IP组心肌SOD活性升高,MDA含量降低,血清TNF-α和IL-6浓度降低,心肌HIF-1α和HO-1的mRNA和蛋白表达上调,HO-1活性升高,心肌梗死面积减小(P＜0.01);与IP组比较,HI组心肌SOD活性降低,MDA含量升高,血清TNF-α和IL6浓度升高,心肌HO-1的mRNA和蛋白表达下调,HO-1活性降低,心肌梗死面积增加(P＜0.05或0.01),心肌HIF-1α的mBNA和蛋白表达差异无统计学意义(P＞0.05).结论缺血预处理减轻大鼠心肌缺血再灌注损伤的机制与HIF-1α诱导HO-1活性增强有关.
목적 탐토결혈예처리대대서결혈재관주심기저양유도인자1α(HIF-1α)화혈홍소가양매1(HO-1)적영향.방법 건강웅성SD대서48지,체중220～280 g,수궤분위4조(n=12):가수술조(S조)、결혈재관주조(IR조)、결혈예처리+결혈재관주조(IP조)화결혈예처리+결혈재관주+HO-1억제제조(HI조).채용결찰좌관상동맥전강지30 min재관주120 min적방법건립심기결혈재관주모형.S조부재관상동맥하천선;IP조우결혈전채용결찰/방송좌관상동맥전강지각5 min,중복3차적방법행결혈예처리;HI조우결혈예처리전1 d복강주사자원계람Ⅸ 10 ms/ks,기여동IP조.우재관주결속시측정심기HIF-1α、HO-1적mRNA화단백표체、HO-1활성、SOD활성급MDA함량,계산심기경사면적,취동맥혈양측정혈청TNF-α화IL-6적농도.결과 여S조비교,IR조、IP조화HI조심기SOD활성강저,MDA함량승고,혈청TNF-α화IL-6적농도승고(P＜0.01);여IR조비교,IP조심기SOD활성승고,MDA함량강저,혈청TNF-α화IL-6농도강저,심기HIF-1α화HO-1적mRNA화단백표체상조,HO-1활성승고,심기경사면적감소(P＜0.01);여IP조비교,HI조심기SOD활성강저,MDA함량승고,혈청TNF-α화IL6농도승고,심기HO-1적mRNA화단백표체하조,HO-1활성강저,심기경사면적증가(P＜0.05혹0.01),심기HIF-1α적mBNA화단백표체차이무통계학의의(P＞0.05).결론 결혈예처리감경대서심기결혈재관주손상적궤제여HIF-1α유도HO-1활성증강유관.
Objective To investigate the effect of ischemic preconditioning(IP)on hypoxia inducible factor-1α(HIF-1α)and heme oxygenase-1(HO-1)in myocardium after myocardial ischemia-reperfusian(I/R)injury in rata and the mechanism.Methods Forty-eight male SD rata weighing 220-280 g were randomly divided into 4 groups(n= 12 each): group A sham operation;group B I/R;group C IP+I/R and group DIP+IR+HO-1 inhibitor.The animals were anesthetized with intraperitoneal 20% urethane 1 g/kg,tracheoatomized and mechanically ventilated.Myocardial ischemia was induced by 30 min occlusion of left anterior descending branch(LAD)of coronary artery followed by 120 min reperfusion,Ischemic preconditioning was induced by 3 episodes of5 min occlusion of LAD at 5 min intervals before myocardial ischemia.Group D received HO-1 inhibitor ZnPP Ⅸ10 mg/kg one day before IP.At the end of 120 min reperfusion the infarct size was measured,the expression of HIF-1α and HO-1 mRNA and protein,SOD and HO-1 activities and MDA content in myocardium and serum TNF-αand IL-6 concentrations were determined.Results Compared with sham operation group,I/R significantly increased MDA content in myocardium and serum TNF-α and IL-6 concentrations and decreased SOD activity in myocardium.Compared with I/R group,IP significantly decreased infarct size,increased HIF-1α and HO-1 mRNA and protein expression and HO-1 activity further and decreased serum TNF-α and IL-6 concentrations and myocardial MDA content in group C.In group D ZnPP Ⅸ pretreatment greatly increased infarct size which was significantly larger than that in group I/R and group IP+I/R.Conclusion IP can protect against myocardial I/R injury.Increase in HO-1 activity induced by HIP-1α may be involved in the underlying mechanism.