缺血后处理大鼠骨骼肌I/R损伤中mTOR的表达及作用
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胡新华 E-mail:xinhuahu@126.com

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国家自然科学基金资助项目(30872527, 30801123)。


The effect of mTOR in ischemic postconditioning-induced attenuation of ischemia/reperfusion injury in rat skeletal muscle
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    摘要:

    目的:探讨雷帕霉素靶蛋白(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)损伤中的表达及其意义。
    方法:48只雄性健康Wistar大鼠,以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,缺血预处理(IPC)组(5 min缺血/5 min再灌,3个循环)及I-postC组(1 min再灌/1 min缺血,3个循环)(n=16), 以大鼠左后肢为对照。分别于再灌注后12,24 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)和雷帕霉素靶蛋白的表达的变化。

    结果: I-postC和IPC组的骨骼肌水肿明显减轻,MDA和MPO亦明显降低,与I/R组比较差异有统计学意义(P<0.05)。I-postC组和IPC组之间无差异(P>0.05)。I-postC与IPC组mTOR蛋白产物表达显著增加,与I/R组比较差异有统计学意义(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,即通过激活mTOR信号转导通路发挥作用。

    Abstract:

    Objective:To study the expression and effect of mammalian target of rapamycin (mTOR) on rat skeletal muscle ischemia-reperfusion(I/R) treated by ischemic postconditioning (I-postC). 
    Methods:Forty-eight healthy male Wistar rats were randomly divided into three groups (n=16):I/R group(4-hour ischemia/12-or 24-hour reperfusion),ischemic preconditioning(IPC)group (3 cycles of 5-minute ischemia /5-minute reperfusion) and I-postC group(3 cycles of 1-minute reperfusion/l-minute ischemia). I/R of right hind limb was induced by clamping the right femoral artery,  in each group the left hind limb (the femoral artery was no clamping) as controll. The tissue morphology, wet-to-dry weight (W/D) ratio, malondialdehyde (MDA), myeloperoxidase (MPO) and expression of mTOR in skeletal muscle were and detected compared in the 3 groups.Results:In I-postC and IPC group, the edema, MDA and MPO of skeletal muscle decreased significantly compared with I/R group (P<0.05). There was no significant difference between the I-postC and IPC group(P<0.05).Compared with I/R group, expression of mTOR increased significantly in I-postC and IPC group(P<0.05)
    Conclusions:I-postC can attenuate I/R injury of the hind limbs in rats, which may be accomplished by activation of mTOR signal pathway. The mechanism of the effect of I-postC  my by as the same as IPC.

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曹辉|胡新华|何家安|刘程伟|辛世杰.缺血后处理大鼠骨骼肌I/R损伤中mTOR的表达及作用[J].中国普通外科杂志,2010,19(12):1302-1305.
DOI:10.7659/j. issn.1005-6947.2010.12.013

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  • 收稿日期:2010-05-05
  • 最后修改日期:2010-07-12
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  • 在线发布日期: 2010-12-15