CAJ | 학술논문

目的探讨哺乳类动物雷帕霉素靶蛋白(mTOR)信号转导通路在缺血后处理(I-postC)减轻大鼠骨骼肌缺血再灌注(I/R)损伤中的表达和意义.方法 48只雄性健康Wistar大鼠,无创动脉夹夹闭右侧股动脉4 h,松夹再灌注12 h或24 h建立大鼠右后肢I/R损伤模型,随机分为I/R组(n=16)、缺血预处理(IPC)组(5 min缺血/5 min再灌,3个循环,n=16)及缺血后处理(IpostC)组(1 min再灌/1 min缺血,3个循环,n=16).分别于再灌注后12 h、24 h取标本.观察骨骼肌组织形态学、湿,干重比、丙二醛(MDA)及髓过氧化物酶(MPO)的变化,Western blot和免疫组织化学方法检测mTOR的表达.结果 I-postC和IPC组的骨骼肌水肿明显减轻,MDA和MPO指标亦明显降低,与I/R组比较差异显著(P＜0.05).I-postC组和IPC组之间无显著差异(P＞0.05).I-postC和IPC组mTOR蛋白产物表达显著增加,与I/R组比较差异显著(P＜0.05).结论 I-postC减轻大鼠后肢骨骼肌I/R损伤,与缺血预处理可能存在共同的作用机制,及通过激活mTOR信号转导通路发挥作用.
목적 탐토포유류동물뢰파매소파단백(mTOR)신호전도통로재결혈후처리(I-postC)감경대서골격기결혈재관주(I/R)손상중적표체화의의.방법 48지웅성건강Wistar대서,무창동맥협협폐우측고동맥4 h,송협재관주12 h혹24 h건립대서우후지I/R손상모형,수궤분위I/R조(n=16)、결혈예처리(IPC)조(5 min결혈/5 min재관,3개순배,n=16)급결혈후처리(IpostC)조(1 min재관/1 min결혈,3개순배,n=16).분별우재관주후12 h、24 h취표본.관찰골격기조직형태학、습,간중비、병이철(MDA)급수과양화물매(MPO)적변화,Western blot화면역조직화학방법검측mTOR적표체.결과 I-postC화IPC조적골격기수종명현감경,MDA화MPO지표역명현강저,여I/R조비교차이현저(P＜0.05).I-postC조화IPC조지간무현저차이(P＞0.05).I-postC화IPC조mTOR단백산물표체현저증가,여I/R조비교차이현저(P＜0.05).결론 I-postC감경대서후지골격기I/R손상,여결혈예처리가능존재공동적작용궤제,급통과격활mTOR신호전도통로발휘작용.
Objective To study the expression of mammalian target of rapamycin(mTOR)in ischemic postconditioning(I-postC)-induced attenuation of ischemia/reperfusion(I/R)injury in rat skeletal muscle.Methods A total of 48 healthy male Wistar rats were randomly divided into 3 groups(n=16 each group):I/R group(4-hour ischemia followed by 12-or 24-hour reperfusion),ischemic preconditioning (IPC)group(3 cycles of 5-minute ischemia followed by 5-minute reperfusion),and I-postC group(3 cycles of 1-minute reperfusion followed by 1-minute ischemia).The rat model of I/R injury in right hind limb model was established by clamping the right femoral artery.The changes in the morphology,wet-to-dry weight ratio(W/D),malondialdehyde(MDA),and myeloperoxidase(MPO)in skeletal muscle were compared.The expression of mTOR was detected by Western blot and immunohistochemistry.Results In I-postC and IPC groups,the skeletal muscle edema was less severe,the levels of MDA and MPO significantly decreased,and the expression of mTOR significantly in creased,compared with I/R group(all P＜0.03).There was no significant difference between I-postC and IPC groups.Conclusion Ipostc may attenuate I/R injury in rat hind limbs by activating mTOR signal pathway,which is similar to the mechanism of IPC.