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一氧化氮合酶、MPT 孔和蛋白激酶 A 在阿片受体激动剂 Delta 啡 II 心脏保护作用中的作用。

The Role of NO Synthase, MPT pore, and Protein Kinase A in the Cardioprotective Effect of the Opioid Receptor Agonist Deltorphin II.

机构信息

Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russia.

Branch of M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, Moscow region, Russia.

出版信息

Bull Exp Biol Med. 2023 Apr;174(6):745-748. doi: 10.1007/s10517-023-05784-4. Epub 2023 May 10.

DOI:10.1007/s10517-023-05784-4
PMID:37160797
Abstract

In male Wistar rats, coronary occlusion (45 min) and reperfusion (120 min) were modeled. Selective δ-opioid receptor agonist (deltorphin II, 0.12 mg/kg) was administered intravenously 5 min before reperfusion; NO synthase inhibitor (L-NAME, 10 mg/kg), MPT pore blocker (atractyloside, 5 mg/kg), and protein kinase A inhibitor (H-89, 10 μg/kg) were administered intravenously 10 min before reperfusion. Deltorphin II administered before reperfusion led to a 2-fold decrease in the infarct size. The infarct-limiting effect of deltorphin II was associated with blockade of MPT pore. Protein kinase A and NO synthase were not involved in the cardioprotective effect of deltorphin II.

摘要

在雄性 Wistar 大鼠中,建立了冠状动脉闭塞(45 分钟)和再灌注(120 分钟)模型。选择性 δ-阿片受体激动剂(deltorphin II,0.12mg/kg)在再灌注前 5 分钟静脉注射;一氧化氮合酶抑制剂(L-NAME,10mg/kg)、MPT 孔阻滞剂(远志糖苷,5mg/kg)和蛋白激酶 A 抑制剂(H-89,10μg/kg)在再灌注前 10 分钟静脉注射。再灌注前给予 deltorphin II 可使梗死面积减少 2 倍。deltorphin II 的梗死限制作用与 MPT 孔的阻断有关。蛋白激酶 A 和一氧化氮合酶不参与 deltorphin II 的心脏保护作用。

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本文引用的文献

1
δ-Opioid Receptors as a Target in Designing New Cardioprotective Drugs: the Role of Protein Kinase C, AMPK, and Sarcolemmal K Channels.δ-阿片受体作为设计新型心脏保护药物的靶点:蛋白激酶 C、AMP 激活的蛋白激酶和肌浆网钙通道的作用。
Bull Exp Biol Med. 2022 May;173(1):33-36. doi: 10.1007/s10517-022-05487-2. Epub 2022 May 27.
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Pharmacology of mitochondrial permeability transition pore inhibitors.线粒体通透性转换孔抑制剂的药理学。
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心肌保护的分子基础:缺血预处理、后处理和远程处理中的信号转导。
Circ Res. 2015 Feb 13;116(4):674-99. doi: 10.1161/CIRCRESAHA.116.305348.
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Acute and chronic cardioprotection by the enkephalin analogue, Eribis peptide 94, is mediated via activation of nitric oxide synthase and adenosine triphosphate-regulated potassium channels.脑啡肽类似物 Eribis 肽 94 通过激活一氧化氮合酶和三磷酸腺苷调节的钾通道实现急性和慢性心脏保护作用。
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Activation of peripheral delta2 opioid receptors increases cardiac tolerance to ischemia/reperfusion injury Involvement of protein kinase C, NO-synthase, KATP channels and the autonomic nervous system.外周δ2阿片受体的激活增加心脏对缺血/再灌注损伤的耐受性 蛋白激酶C、一氧化氮合酶、ATP敏感性钾通道及自主神经系统的参与
Life Sci. 2009 May 8;84(19-20):657-63. doi: 10.1016/j.lfs.2009.02.016. Epub 2009 Feb 24.
7
Cardioprotective effect of chronic hypoxia is blunted by concomitant hypercapnia.慢性低氧血症的心脏保护作用会因同时存在的高碳酸血症而减弱。
Physiol Res. 2003;52(2):171-5.
8
Ischemic preconditioning and morphine-induced cardioprotection involve the delta (delta)-opioid receptor in the intact rat heart.在完整大鼠心脏中,缺血预处理和吗啡诱导的心脏保护作用涉及δ-阿片受体。
J Mol Cell Cardiol. 1997 Aug;29(8):2187-95. doi: 10.1006/jmcc.1997.0454.