PI3K-Akt通路对老年心肌缺血预适应模型大鼠线粒体通透性转换孔开放程度的影响

doi:10.13481/j.1671-587x.20160403

Abstract

Abstract:

Objective: To study the effect of PI3K-Akt signaling pathway on the openness degree of mitochondrial permeability transition pore (mPTP) in the aged model rats of myocardial ischemic preconditioning (IPC),and to clarify its possible mechanism. Methods: Thirty-five Wistar Wistar rats (aged 21-23 months) were randomly divided into ischemia reperfusion (I/R) group,I/R+Wort (Wortmannin,inhibitor of PI3K) group,IPC group and IPC+ Wort group(n=7). The models of I/R and IPC were established and 0.6 mg·kg^-1 Wort were injected to the caudal veins of the rats in Wort group before reperfusion. After 120 min reperfusion,the myocardium tissue protein was extracted,and the Akt and p-Akt protein expression levels were detected by Western blotting method. The myocardial mitochondrial of rats was separated through differential centrifugation,and the superoxide level,SOD level and openness degrees of mPTP were determined by microplate reader. Results: Compared with I/R group (0.288±0.071),the expression level of p-Akt protein in myocardium tissue of the rats in IPC group (0.346±0.051) was increased (P < 0.05),and the expression level of p-Akt im myocardium tissue of the rats in I/R+Wort group (0.044±0.010) was decreased (P < 0.01).Compared with I/R group (0.216±0.024),the superoxide level in mitochondrial of the rats in IPC group (0.187±0.022) was decreased (P < 0.05),and the superoxide level in mitochondrial in I/R+Wort group (0.218±0.029) had no significant change (P > 0.05). Compared with I/R group (1.15±0.15),the SOD activity in mitochondrial of the rats in IPC group (1.39±0.14) was increased (P < 0.05),and the SOD activity in mitochondrial of the rats in I/R+Wort group (1.17±0.21) had no significant change (P > 0.05). Compared with I/R group,the mPTP openness degree in IPC group was decreased (P < 0.05)during 6 to 2 min,however the openness degree in I/R+Wort group had no significant change (P > 0.05). Compared with IPC group, the mPTP openness degree in IPC+Wort group was increased (P < 0.05). Conclusion: The IPC of aged rats can inhibit the openness of mitochondrial permeability transition pore through activating the PI3K-Akt signaling pathway.

Key words: ischemia reperfusion, ischemic preconditioning, phosphatidylinositol-3 kinase, protein kinase B, mitochondrial permeability transition pore

CLC Number:

R541.4

WEI Yanhong, LIU Xiaodong, LIU Yan, LU Lijuan. Effect of PI3K-Akt signaling pathway on openness degree of mitochondrial permeability transition pore in aged model rats of myocardial ischemic preconditioning[J].Journal of Jilin University Medicine Edition, 2016, 42(04): 648-652.

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Effect of PI3K-Akt signaling pathway on openness degree of mitochondrial permeability transition pore in aged model rats of myocardial ischemic preconditioning

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