Dark chocolate receptors: epicatechin-induced cardiac protection is dependent on δ-opioid receptor stimulation
Dark chocolate receptors: epicatechin-induced cardiac protection is dependent on δ-opioid receptor stimulation
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DOI：
10.1152/ajpheart.00073.2010
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发表时间：
2010-11-01
影响因子：
4.8
通讯作者：
Patel, Hemal H.
中科院分区：
文献类型：
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作者：
Panneerselvam, Mathivadhani;Tsutsumi, Yasuo M.;Patel, Hemal H.
Panneerselvam M，Tsutsumi YM，Bonds JA，Horikawa YT，Saldana M，道尔顿ND，Head BP，Patel PM，Roth DM，Patel HH.黑巧克力受体：表儿茶素诱导的心脏保护依赖于β-阿片受体刺激。美国生理学杂志心脏循环生理学299：H1604-H1609，2010年。首次发表于2010年9月10日; doi：10.1152/ajpheart.00073.2010.-表儿茶素是一种黄酮类化合物，是一种众所周知的抗氧化剂，与人类和动物的各种保护作用有关。特别是，它在预防心血管疾病方面的作用已被流行病学研究所证实。低剂量表儿茶素，不具有显着的抗氧化活性，也是保护;然而，低剂量表儿茶素诱导这种效果的机制是未知的。我们的实验室测试了低剂量表儿茶素通过阿片受体激活介导心脏保护的假设。将C57 BL/6小鼠随机分配至10组中的1组：对照，表儿茶素，纳洛酮（非选择性阿片受体拮抗剂）、表儿茶素+纳洛酮、纳曲吲哚（δ-特异性阿片受体拮抗剂），表儿茶素+纳曲吲哚，norbinaltorphimine（nor-BNI，κ特异性阿片受体拮抗剂），表儿茶素+ nor-BNI，5-羟基癸酸[5-HD，ATP敏感性钾通道拮抗剂]，和表儿茶素+5-HD。分别通过口服管饲法或腹膜内注射给予表儿茶素（lmg/kg）或其他抑制剂（5 mg/kg），每天持续10天。使小鼠经受30分钟冠状动脉闭塞，随后再灌注2小时，并且通过面积测量法测定梗塞大小。测定全心脏匀浆的下游阿片受体信号传导靶点。与对照小鼠相比，表儿茶素和表儿茶素+去甲BNI处理的小鼠的梗死面积显着减少。这种保护作用可被纳洛酮、纳曲吲哚和5-HD阻断。表儿茶素和表儿茶素+ nor-BNI增加Src、Akt和I κ B α的磷酸化，同时降低c-Jun NH 2-末端激酶和半胱天冬酶激活的DNA酶的表达。所有信号传导效应与阿片受体刺激和随后的心脏保护一致。纳洛酮、纳曲吲哚和5-HD可减弱这些作用。总之，表儿茶素通过阿片受体起作用，更具体地说，通过δ-阿片受体对缺血再灌注损伤产生心脏保护作用。
Panneerselvam M, Tsutsumi YM, Bonds JA, Horikawa YT, Saldana M, Dalton ND, Head BP, Patel PM, Roth DM, Patel HH. Dark chocolate receptors: epicatechin-induced cardiac protection is dependent on beta-opioid receptor stimulation. Am J Physiol Heart Circ Physiol 299: H1604-H1609, 2010. First published September 10, 2010; doi:10.1152/ajpheart.00073.2010.-Epicatechin, a flavonoid, is a well-known antioxidant linked to a variety of protective effects in both humans and animals. In particular, its role in protection against cardiovascular disease has been demonstrated by epidemiologic studies. Low-dose epicatechin, which does not have significant antioxidant activity, is also protective; however, the mechanism by which low-dose epicatechin induces this effect is unknown. Our laboratory tested the hypothesis that low-dose epicatechin mediates cardiac protection via opioid receptor activation. C57BL/6 mice were randomly assigned to 1 of 10 groups: control, epicatechin, naloxone (nonselective opioid receptor antagonist), epicatechin + naloxone, naltrindole (delta-specific opioid receptor antagonist), epicatechin + naltrindole, norbinaltorphimine (nor-BNI, kappa-specific opioid receptor antagonist), epicatechin + nor-BNI, 5-hydroxydecanoic acid [5-HD, ATP-sensitive potassium channel antagonist], and epicatechin + 5-HD. Epicatechin (1 mg/kg) or other inhibitors (5 mg/kg) were administered by oral gavage or intraperitoneal injection, respectively, daily for 10 days. Mice were subjected to 30 min coronary artery occlusion followed by 2 h of reperfusion, and infarct size was determined via planimetry. Whole heart homogenates were assayed for downstream opioid receptor signaling targets. Infarct size was significantly reduced in epicatechin- and epicatechin + nor-BNI-treated mice compared with control mice. This protection was blocked by naloxone, naltrindole, and 5-HD. Epicatechin and epicatechin + nor-BNI increased the phosphorylation of Src, Akt, and I kappa B alpha, while simultaneously decreasing the expression of c-Jun NH2-terminal kinase and caspase-activated DNase. All signaling effects are consistent with opioid receptor stimulation and subsequent cardiac protection. Naloxone, naltrindole, and 5-HD attenuated these effects. In conclusion, epicatechin acts via opioid receptors and more specifically through the delta-opioid receptor to produce cardiac protection from ischemia-reperfusion injury.