脂联素后处理对大鼠心肌缺血/再灌注损伤的影响及ADP/PI3K/Akt信号通路的作用

doi:10.12047/j.cjap.5531.2017.075

中国应用生理学杂志 ›› 2017, Vol. 33 ›› Issue (4): 308-313.doi: 10.12047/j.cjap.5531.2017.075

脂联素后处理对大鼠心肌缺血/再灌注损伤的影响及ADP/PI3K/Akt信号通路的作用

赵林静¹, 崔柳苏¹, 张金盈², 王永玲¹

1. 新乡医学院基础医学院, 河南新乡 453003;
2. 郑州大学第一附属医院心血管内科, 河南郑州 450000

收稿日期:2016-11-28 修回日期:2017-05-15 出版日期:2017-07-28 发布日期:2018-06-19
通讯作者: 赵林静,Tel:15893803331;E-mail:nic315@sina.com E-mail:nic315@sina.com
基金资助:
新乡医学院博士科研启动基金资助（XYBSKYZZ 201634）

Effect of adiponectin postconditioning against myocardial ischemia/reperfusion injury in rats and role of ADP/PI3K/Akt pathway in adiponectin postconditioning

ZHAO Lin-jing¹, CUI Liu-su¹, ZHANG Jin-ying², WANG Yong-ling¹

1. School of Basic Medicine, Xinxiang Medical University, Xinxiang 453003;
2. Department of Vasculocardiology, First Affiliated Hospital, Zhengzhou University, Zhengzhou 450000, China

Received:2016-11-28 Revised:2017-05-15 Online:2017-07-28 Published:2018-06-19
Supported by:
新乡医学院博士科研启动基金资助（XYBSKYZZ 201634）

摘要/Abstract

摘要： 目的：探讨脂联素（ADP）后处理对大鼠心肌缺血/再灌注损伤（MIRI）的影响以及脂联素/磷脂酰肌醇-3激酶/蛋白激酶B （ADP/PI3K/Akt）通路的作用。方法：SD大鼠麻醉后气管插管连接呼吸机，开胸暴露心肌，在左心耳和肺动脉圆锥之间用带线圆针对冠脉左前降支（LAD）穿线，LAD结扎断流30 min后松线再灌注120 min，建立大鼠MIRI模型。大鼠随机分为以下5组（n=12）：①假手术组（Sham组）：LAD仅穿线不结扎；② MIRI组；③ADP后处理组（ADP组）：LAD断流10 min时静注ADP继续断流20 min，然后再灌注120 min；④ADP+LY294002组：LAD断流10 min时静注ADP和LY294002，其余同ADP组；⑤LY294002组：LAD断流10 min时静注LY294002，其余同ADP组。各组取血检测LDH和cTnI含量，取左心室心肌测定PI3k、Akt、p-Akt、ADPmRNA、ADPR1mRNA和PI3KmRNA表达。结果：与Sham组比较，MIRI组血浆LDH和cTnI均明显升高（P<0.05）；和MIRI组相比，ADP组心肌损伤指标明显下降（P<0.05），而应用LY294002的两组心肌损伤比ADP组加重（P<0.05）。ADP组心肌PI3K、p-Akt、ADPmRNA、ADPR1mRNA和PI3kmRNA表达比MIRI组升高（P<0.05），应用LY294002两组上述5个指标比MIRI组降低（P<0.05）。结论：ADP后处理对大鼠MIRI有保护作用，ADP/PI3K/Akt通路参与了以上作用。

关键词: 脂联素, 缺血后处理, 心肌缺血/再灌注损伤, 信号转导通路, 磷脂酰肌醇-3激酶, 磷酸化的蛋白激酶B, 大鼠

Abstract: Objective: To investigate the effects of adiponectin(ADP) postconditioning against myocardial ischemia/reperfusion injury(MIRI) in rats and role of ADP/PI3K/Akt pathway in ADP postconditioning.Methods: SD rat was connected to ventilator by tracheal intubation under anesthesia, then left anterior descending coronary artery (LAD) was threaded between left auricle and pulmonary artery cone after exposing heart by surgery. MIRI model was induced by ligation of LAD for 30 min and the following reperfusion for 120 min. Rats were divided randomly into 5 groups (n=12):① Sham group:LAD was threaded without ligation; ② MIRI group; ③ADP group (ADP postconditioning) were subjected to intravenous injection of ADP when LAD ligation for 10 min and the ligation held for 20 min after that, then reperfusion for 120 min; ④ ADP+LY294002 group were subjected to injection of ADP and LY294002 when LAD ligation for 10 min, the other steps were the same as ADP group; ⑤ LY294002 group were subjected to injection of LY294002 when LAD ligation for 10 min, the other steps were the same as ADP group. Titers of lactate dehydrogenase(LDH) and cardiac troponin I(cTnI) in plasma were observed, expressions of PI3K, Akt, phosphorylated-Akt(p-Akt), ADP mRNA, ADPR1 mRNA and PI3k mRNA in myocardial tissue were measured.Results: Compared with sham group, the levels of LDH and cTnI in MIRI group were increased (P<0.05); Compared with MIRI group, the levels of LDH and cTnI in ADP group were decreased (P<0.05); Compared with ADP group, the levels of LDH and cTnI were increased in LY294002 applying groups(P<0.05). Compared with MIRI group, the expressions of PI3K, p-Akt, ADP mRNA, ADPR1 mRNA and PI3K mRNA were increased in ADP group (P<0.05), the above mentioned 5 parameters in LY294002 applying groups were decreased(P<0.05).Conclusion: ADP postconditioning could reduce MIRI in rats, the protective effect might have relation to ADP/PI3k/Akt pathway.

Key words: adiponectin, ischemic postconditioning, myocardial ischemia/reperfusion injury, signalling pathway, PI3K, p-Akt, rat

赵林静, 崔柳苏, 张金盈, 王永玲. 脂联素后处理对大鼠心肌缺血/再灌注损伤的影响及ADP/PI3K/Akt信号通路的作用[J]. 中国应用生理学杂志, 2017, 33(4): 308-313.

ZHAO Lin-jing, CUI Liu-su, ZHANG Jin-ying, WANG Yong-ling. Effect of adiponectin postconditioning against myocardial ischemia/reperfusion injury in rats and role of ADP/PI3K/Akt pathway in adiponectin postconditioning[J]. CJAP, 2017, 33(4): 308-313.

参考文献

[1] Li P, Shibata R, Maruyama S, et al. Fenofibrate promotes ischemia-induced rev ascularization through the adiponectin-dependent pathway[J]. Am J Physiol Endocrinol Metab. 2010, 299(4):E560-566.
[2] 吴芹, 孙红, 杨留才, 等. 热量限制通过AMPK途径恢复老年大鼠心脏缺血预处理效应的实验观察[J]. 中国老年学, 2011, 31(1):77-80.
[3] 高建芝, 吕风华, 张金盈. 脂联素及其受体信号通路在肢体缺血预适应对心肌保护中的作用[J]. 中华老年医学杂志, 2012, 31(5):434-437.
[4] 赵林静, 高建芝, 腾清蕾, 等. 脂联素改善大鼠肢体缺血预适应对缺血-再灌注心肌的保护效应[J]. 实用医学杂志, 2013, 29(1):40-42.
[5] 黄晓玲, 陈柏梁, 仇烨, 等. 血清肌钙蛋白I,血浆脑钠肽联合心脏Tei指数评估窒息新生儿心肌损伤及心功能[J]. 中华实用儿科临床杂志, 2014, 29(14):1112-1114.
[6] Leonardi F, Passeri B, Fusari A, et al. Cardiac troponin I (cTnI) co ncentrati on in an ovine model of myocardial ischemia[J]. Res Vet Sci. 2008, 85(1):141-144.
[7] 卢彦珍, 王佳, 张翠英, 等. 缺血后处理对缺血/再灌注大鼠心肌间质保护效应机制的探讨[J]. 中国应用生理学杂志, 2014, 30(5):431-435.
[8] 卢彦珍, 王佳, 宋娟, 等. 缺血后处理对缺血/再灌注大鼠心肌基质金属蛋白酶-2表达的影响[J]. 中国应用生理学杂志, 2014, 30(1):81-84.
[9] 曹广运, 谢瑞芹, 崔炜, 等. 骨骼肌和心肌缺血后处理对兔缺血/再灌注心肌的保护作用[J]. 中国应用生理学杂志, 2012, 28(5):476-480.
[10] Fang X, Palanivel R, Cresser J, et al. An APPLI-AMPK sig naling axis mediates beneficial metabolic effects of adiponectin in the heart[J]. Am J Physiol E ndocrinol Metab. 2010, 299(5):E721-729.
[11] Cao T, Gao Z, Gu L, et al. AdipoR1/APPL1 potentiates the pro tective effects of globular adiponectin on angiotensin Ⅱ-induced cardiac hypertrophy and fibrosis in neonatal rat atrial myocytes and fibroblasts[J]. PLoS One. 2014, 9(8):e103793.
[12] Denzel MS, Scimia MC, Zumstein PM, et al. T-cadherin is cri tical for adipone ctin-mediated cardioprotection in mice[J]. J Clin Invest. 2010, 120(12):4342-4352.
[13] Wijesekara N,Krishnamurthy M,Bhattacharjee A,et al. Adipo nectin-induced E RK and Akt phosphorylation protects against pancreatic beta cell apoptosis and increases insulin gene expression and secretion[J].J Biol Chem. 2010, 285(44):33623-33631.
[14] Weickhardt AJ,Tebbutt NC,Mariadason JM.Strategies for overcomi ng inhere nt and acquired resistance to EGFR inhibitors by targeting downstream effectors in the RAS/PI3K pathway[J]. Curr Cancer Drug Targets. 2010, 10(8):824-833.
[15] Gu X, Feng Y, Shi C, et al. Antiapoptotic mechanism of in sulin in reoxygenat ion-induced injury in cultured cardiomyocytes of neonatal rats[J]. J Huazh ong Univ Sci Technolog Med Sci. 2005, 25(6):632-635.
[16] Inamura Y, Miyamae M, Sugioka S, et al. Sevoflurane postcondi tioning prevents ac tivation of caspase-3 and caspase-9 through antiapoptotic signaling after myoc ardial ischemia reperfusion[J]. J Anesth. 2010, 24(2):215-224.
[17] 陈珊珊, 金红芳, 杜军保, 等. 磷脂酰肌醇-3激酶/丝氨酸苏氨酸蛋白激酶信号通路对异丙肾上腺素所致大鼠心肌损伤的作用[J]. 中华实用儿科临床杂志, 2012, 27(7):534-536.
[18] 范志宇, 李春雨, 秦超毅, 等. 磷脂酰肌醇-3激酶通路对大鼠肺动脉平滑肌细胞分化状态和增殖活性的调控作用[J]. 中华实用儿科临床杂志, 2013, 28(18):1417-1421.
[19] Guo J, Bian Y, Bai R, et al. Globular adiponectin attenuates myocardial isch emia/reperfusion injury by upregulating endoplasmic reticulum Ca²⁺-ATPase activi ty and inhibiting endoplasmic reticulum stress[J]. J Cardiovasc Pharmacol. 2013, 62(2):143-153.
[20] Wang T, Mao X, Li H, et al. N-Acetylcysteine and allopurinol up-regulated the Jak/STAT3 and PI3K/Akt pathways via adiponectin and attenuated myocardial pos tischemic injury in diabetes[J]. Free Radic Biol Med. 2013, 63(10):291-303.

脂联素后处理对大鼠心肌缺血/再灌注损伤的影响及ADP/PI3K/Akt信号通路的作用

Effect of adiponectin postconditioning against myocardial ischemia/reperfusion injury in rats and role of ADP/PI3K/Akt pathway in adiponectin postconditioning

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