CAJ | 학술논문

目的观察PI3K/Akt在深低温低流量(DHLF)脑保护中的作用并探讨其机制.方法 Akt1+/-小鼠与野生型(WT)小鼠各48只分别随机并平均的分为假手术组与手术组.手术组在深低温下钳闭颈总动脉120 min并重新开放,模拟DHLF过程.各组脑血流经激光多普勒血流仪监测.经TUNEL和Western blot检测各组脑细胞凋亡及Akt下游bcl-2与bax的改变.结果阻断颈总动脉后,小鼠脑血流量减少86%以上.野生型手术组死亡率在再灌注24h后约为15%,72h死亡率达到20%,而Akt1+/-小鼠死亡率增加,24h后约为25%,72 h达到40%(P<0.05).Akt1+/-脑细胞凋亡数量增多(P<0.01),Western blot显示Akt下游bcl-2与bax表达增强.结论抑制Akt1后小鼠脑损害程度加重,PI3K/Akt通过抑制线粒体凋亡通路发挥作用.
목적 관찰PI3K/Akt재심저온저류량(DHLF)뇌보호중적작용병탐토기궤제.방법 Akt1+/-소서여야생형(WT)소서각48지분별수궤병평균적분위가수술조여수술조.수술조재심저온하겸폐경총동맥120 min병중신개방,모의DHLF과정.각조뇌혈류경격광다보륵혈류의감측.경TUNEL화Western blot검측각조뇌세포조망급Akt하유bcl-2여bax적개변.결과 조단경총동맥후,소서뇌혈류량감소86%이상.야생형수술조사망솔재재관주24h후약위15%,72h사망솔체도20%,이Akt1+/-소서사망솔증가,24h후약위25%,72 h체도40%(P<0.05).Akt1+/-뇌세포조망수량증다(P<0.01),Western blot현시Akt하유bcl-2여bax표체증강.결론 억제Akt1후소서뇌손해정도가중,PI3K/Akt통과억제선립체조망통로발휘작용.
Objective To investigate the genetic effect of PI3K/Akt signaling pathway in Akt1+/-mice after deep hypothermia low flow ( DHLF). Methods Ninety-six Akt1+/- and wild-type C57/B6 mice were randomly and equally divided into sham-operation and operation groups. The Akt1+/- and wild type of C57BL/6 mice underwent bilateral common carotid arteries occlusion for 120 min at (18.5 ± 0. 5)℃. and then reopened and rewarmed, while the sham-operation group excluded the occlusion. Regional cerebral blood flow (rCBF) was determined by laser Doppler flowmetry (LDF). By using TUNEL and Western blotting, the apoptotic level of cerebral cells and expression of bcl-2 and bax were examined. Results rCBF was decreased by at least 86% after occlusion. Mortality of Akt1+/- mice was increased to 25% after 24 h of cerebral reperfusion and 40% after 72 h (P <0. 05). Western blotting showed the expression of bcl-2 and bax at the downstream of Akt1 was increased. Conclusion Haplo-insufficiency of Akt1 exacerbates cerebral injury after DHLF. PDK/Akt exerts their roles by inhibiting the apoptosis pathway in mitochondria.