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

吉林大学学报(医学版) ›› 2016, Vol. 42 ›› Issue (04): 648-652.doi: 10.13481/j.1671-587x.20160403

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

韦艳红¹, 刘晓冬², 刘艳¹, 陆丽娟¹

1. 齐齐哈尔医学院附属第三医院全科病房, 黑龙江齐齐哈尔 161000;
2. 吉林大学公共卫生学院卫生部放射生物学重点实验室, 吉林长春 130021

收稿日期:2016-01-26 发布日期:2016-07-20
通讯作者: 韦艳红,副主任医师(Tel:0452-2944158,E-mail:qysyweiyh@163.com) E-mail:qysyweiyh@163.com
作者简介:韦艳红(1971-),女,黑龙江省齐齐哈尔市人,副主任医师,医学硕士,主要从事老年心脑血管疾病方面的研究。
基金资助:
国家自然科学基金资助课题（81573082）

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

WEI Yanhong¹, LIU Xiaodong², LIU Yan¹, LU Lijuan¹

1. Department of General Medicine, Third Affiliated Hospital, Qiqihar Medical University, Qiqihar 161000, China;
2. Key Laboratory of Radiobiology, Ministry of Health, School of Public Health, Jilin University, Changchun 130021, China

Received:2016-01-26 Published:2016-07-20

摘要/Abstract

摘要：

目的：探讨PI3K-Akt通路对老年心肌缺血预适应（IPC）模型大鼠线粒体通透性转换孔（mPTP）开放程度的影响，阐明其可能机制。方法：21~23月龄Wistar大鼠35只随机分为缺血再灌注（I/R）组、I/R+PI3K抑制剂Wortmannin（Wort）组、IPC组、IPC+Wort组和假手术组，每组7只。分别建立I/R、IPC模型，Wort组大鼠再灌注前尾静脉注射Wort 0.6 mg·kg^-1。120 min再灌注结束后，提取心肌组织蛋白，Western blotting法检测大鼠心肌组织中Akt及p-Akt蛋白相对表达水平。差速离心法分离大鼠心肌线粒体，酶标仪检测线粒体内超氧化物水平、超氧化物歧化酶（SOD）活性及心肌mPTP开放程度。结果：与I/R组（0.288±0.071）比较，IPC组大鼠心肌组织p-Akt蛋白相对表达水平（0.346±0.051）明显升高（P < 0.05），I/R+Wort组大鼠心肌组织中p-Akt蛋白相对表达水平（0.044±0.010）明显降低（P < 0.01）。与I/R组（0.216±0.024）比较，IPC组大鼠粒线粒体超氧化物水平（0.187±0.022）明显降低（P < 0.05），I/R+Wort组大鼠粒线粒体超氧化物水平（0.218±0.029）无明显变化（P > 0.05）。与I/R组（1.15±0.15）比较，IPC组大鼠线粒体SOD活性（1.39±0.14）明显升高（P < 0.05），I/R+Wort组大鼠线粒体SOD活性（1.17±0.21）无明显变化（P > 0.05）。在6~20min时，与I/R组比较，IPC组大鼠心肌mPTP开放程度明显降低（P < 0.05），I/R+Wort组大鼠心肌mPTP开放程度无明显变化（P > 0.05）；与IPC组比较，IPC+Wort组大鼠心肌mPTP开放程度明显增加（P < 0.05）。结论：老年大鼠IPC可通过激活PI3K-Akt通路抑制心肌mPTP的开放。

关键词: 缺血再灌注, 缺血预适应, 磷脂酰肌醇3激酶, 蛋白激酶B, 线粒体通透性转换孔

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

中图分类号:

R541.4

韦艳红, 刘晓冬, 刘艳, 陆丽娟. 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[J]. 吉林大学学报(医学版), 2016, 42(04): 648-652.

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.

参考文献

[1] 宋丽华,张晓一,来丽娜,等.白藜芦醇对心肌缺血再灌注过程中线粒体的保护[J].中国医院药学杂志,2015,35(10):907-911.

[2] Fullmer TM,Pei S,Zhu Y,et al. Insulin suppresses ischemic preconditioning-mediatedcardioprotection through Akt-dependent mechanisms[J]. J Mol Cell Cardiol,2013,64(11):20-29.

[3] 韩劲松,王辉山,韩宏光,等.心肌缺血预适应作用对老年大鼠心肌的影响及其机制的研究[J].中国循环杂志,2014,29(8):624-628.

[4] 韦艳红,刘艳,康晓新,等.依达拉奉对老年大鼠心肌缺血再灌注后线粒体功能的保护作用[J].中国老年学杂志,2015,35(15):4159-4161.

[5] Yang C,Talukder MA,Varadharaj S,et al. Early ischaemic preconditioning requires Akt- and PKA-mediated activation of eNOS via serine1176 phosphorylation[J]. Cardiovasc Res,2013,97(1):33-43.

[6] Rajala RV,Ranjo-Bishop M,Wang Y,et al. The p110α isoform of phosphoinositide 3-kinase is essential for cone photoreceptor survival[J]. Biochimie,2015,112(5):35-40.

[7] 刘祥,景桂霞,白娟,等.舒芬太尼预处理对大鼠心肌缺血再灌注时PI3K/Akt的影响[J].南方医科大学学报,2014,34(3):335-340.

[8] Calviño E,Estañ MC,Sánchez-Martín C,et al. Regulation of death induction and chemosensitizing action of 3-bromopyruvate in myeloid leukemia cells:energy depletion,oxidative stress,and protein kinase activity modulation[J]. J Pharmacol Exp Ther,2014,348(2):324-335.

[9] Peart JN,Pepe S,Reichelt ME,et al. Dysfunctional survival-signaling and stress-intolerance in aged murine and human myocardium[J]. Exp Gerontol,2014,50(2):72-81.

[10] 牛宇杰,赵炜,刘新光,等.活性氧与衰老的研究进展[J].国际老年医学杂志,2014,35(1):33-38.

[11] Zuo L,Pannell BK,Re AT,et al. Po2 cycling protects diaphragm function during reoxygenation via ROS,Akt,ERK,and mitochondrial channels[J]. Am J Physiol Cell Physiol,2015,309(11):759-766.

[12] Rao VK,Carlson EA,Yan SS. Mitochondrial permeability transition pore is a potential drug target for neurodegeneration[J]. Biochim Biophys Acta,2014,1842(8):1267-1272.

[13] 李冬,史大卓,刘秀华,等.线粒体功能障碍与心肌缺血再灌注损伤[J].中华老年心脑血管病杂志,2014,16(3):318-321.

[14] Taliani S,Pugliesi I,Da Settimo F. Structural requirements to obtain highly potent and selective 18 kDa translocator protein (TSPO) ligands[J]. Curr Top Med Chem,2011,11(7):860-886.

[15] Javadov S,Karmazyn M,Escobales N. Mitochondrial permeability transition pore opening as a promising therapeutic target in cardiac diseases[J]. J Pharmacol Exp Ther,2009,330(3):670-678.

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

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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