In vitro and in vivo efficacy of a potent opioid receptor agonist, biphalin, compared to subtype-selective opioid receptor agonists for stroke treatment.
In vitro and in vivo efficacy of a potent opioid receptor agonist, biphalin, compared to subtype-selective opioid receptor agonists for stroke treatment.
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DOI：
10.1016/j.brainres.2015.03.022
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发表时间：
2015-06-03
期刊：
影响因子：
2.9
通讯作者：
Abbruscato, Thomas J.
中科院分区：
文献类型：
--
作者：
Yang, Li;Islam, Mohammad R.;Karamyan, Vardan T.;Abbruscato, Thomas J.
为了应对确定中风新疗法的挑战，本研究旨在使用缺血性中风的体外和体内模型，与亚型选择性 OR 激动剂相比，评估一种有效的非选择性阿片受体 (OR) 激动剂 Biphalin 作为潜在的神经保护候选药物。我们的体外方法包括接受谷氨酸和缺氧/血糖 (H/A) 条件挑战的小鼠原代神经元细胞。根据乳酸脱氢酶 (LDH) 和 3-(4, 5-二甲基噻唑-2-基)-2, 5-二苯基四唑溴化物 (MTT) 测定，我们观察到，与所有选择性阿片类激动剂相比，10 nM Biphalin 在谷氨酸挑战后发挥了统计学上显着的神经保护作用。此外，在所有情况下，与选择性阿片受体激动剂相比，10 nM Biphalin 在 H/A 复氧后提供了更好的神经保护作用。我们的体外研究得到了体内研究的支持，体内研究表明，与任何选择性阿片受体激动剂相比，非选择性阿片受体激动剂 Biphalin 具有增强的神经保护功效，水肿和梗塞比率降低证明了这一点。在两项独立的行为测试中，水肿和梗塞的减少伴随着动物神经系统的改善。总的来说，这些数据强烈表明，用双酞林同时激动剂刺激 mu、kappa 和 delta OR 具有神经保护作用，并且优于激活任何单一 OR 亚型的神经保护作用。
To meet the challenge of identification of new treatments for stroke, this study was designed to evaluate a potent, nonselective opioid receptor (OR) agonist, biphalin, in comparison to subtype selective OR agonists, as a potential neuroprotective drug candidate using in vitro and in vivo models of ischemic stroke. Our in vitro approach included mouse primary neuronal cells that were challenged with glutamate and hypoxic/aglycemic (H/A) conditions. We observed that 10 nM biphalin, exerted a statistically significant neuroprotective effect after glutamate challenge, compared to all selective opioid agonists, according to lactate dehydrogenase (LDH) and 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays. Moreover, 10 nM biphalin provided superior neuroprotection after H/A-reoxygenation compared to selective opioid agonists in all cases. Our in vitro investigations were supported by in vivo studies which indicate that the nonselective opioid agonist, biphalin, achieves enhanced neuroprotective potency compared to any of the selective opioid agonists, evidenced by reduced edema and infarct ratios. Reduction of edema and infarction was accompanied by neurological improvement of the animals in two independent behavioral tests. Collectively these data strongly suggest that concurrent agonist stimulation of mu, kappa and delta ORs with biphalin is neuroprotective and superior to neuroprotection by activation of any single OR subtype.
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影响因子：
3
作者：
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通讯作者：
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