The Akt pathway is involved in rapid ischemic tolerance in focal ischemia in Rats.
The Akt pathway is involved in rapid ischemic tolerance in focal ischemia in Rats.
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DOI：
10.1007/s12975-010-0017-5
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发表时间：
2010-09
影响因子：
6.9
通讯作者：
Zhao H
中科院分区：
文献类型：
--
作者：
Gao X;Zhang H;Steinberg G;Zhao H
尽管延迟缺血预处理的保护机制已得到广泛研究，但很少有研究涉及快速缺血后处理相关的机制。我们研究了快速预处理诱导的缺血耐受是否受Akt生存信号通路的调节。在雄性大鼠中，通过永久性闭塞左侧大脑中动脉远端（MCA）以及双侧颈总动脉（CCA）闭塞30分钟或1小时来诱导脑卒中。在脑卒中发作前1小时进行快速预处理，在CCA闭塞30分钟的大鼠中使梗死面积减少69%，但在CCA闭塞1小时的大鼠中仅减少19%。在CCA闭塞30分钟的对照缺血后，蛋白质印迹法（Western Blot）显示磷酸化Akt（P - Akt）短暂升高，而Akt激酶活性测定显示Akt活性降低。尽管与对照缺血相比，预处理在1小时和5小时时没有改变P - Akt水平，但它减轻了半暗带中5小时时Akt活性的降低。然而，预处理没有改变Akt通路中磷酸化磷脂酰肌醇依赖性激酶1（P - PDK1）、磷酸化磷酸酶和张力蛋白同源物（P - PTEN）以及磷酸化糖原合成酶激酶3β（P - GSK3β）的水平，这些在脑卒中后均降低。最后，磷脂酰肌醇3激酶（PI3K）抑制剂LY294002完全逆转了缺血预处理的保护作用。总之，Akt有助于快速预处理对脑卒中的保护作用。
Although the protective mechanisms of delayed ischemic preconditioning have received extensive studies, few have addressed the mechanisms associated with rapid ischemic postconditioning. We investigated whether ischemic tolerance induced by rapid preconditioning is regulated by the Akt survival signaling pathway. Stroke was generated by permanent occlusion of the left distal middle cerebral artery (MCA) plus 30 min or 1 h occlusion of the bilateral common carotid artery (CCA) in male rats. Rapid preconditioning performed 1h before stroke onset reduced infarct size by 69% in rats with 30 min CCA occlusion, but by only 19% with 1 h occlusion. After control ischemia with 30 min CCA occlusion, Western Blot showed that P-Akt was transiently increased while Akt kinase assay showed that Akt activity was decreased. Although preconditioning did not change P-Akt levels at 1h and 5h compared with control ischemia, it attenuated reduction in Akt activity at 5h in the penumbra. However, preconditioning did not change the levels of P-PDK1, P-PTEN, and P-GSK3β in the Akt pathway, all of which were decreased after stroke. At last, the PI3K kinase inhibitor, LY294002, completely reversed the protection from ischemic preconditioning. In conclusion, Akt contributes to the protection of rapid preconditionin against stroke.
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影响因子：
2.5
作者：
KATO, H;LIU, Y;KOGURE, K
通讯作者：
KOGURE, K
影响因子：
4.2
作者：
Gao, Xuwen;Ren, Chuancheng;Zhao, Heng
通讯作者：
Zhao, Heng
DOI：
10.1097/00004647-200202000-00004
发表时间：
2002-02-01
影响因子：
6.3
作者：
Nakamura, M;Nakakimura, K;Sakabe, T
通讯作者：
Sakabe, T
影响因子：
3.8
作者：
KATO, H;ARAKI, T;KOGURE, K
通讯作者：
KOGURE, K
影响因子：
2.9
作者：
Zhang, Hanfeng;Ren, Chuancheng;Zhao, Heng
通讯作者：
Zhao, Heng