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首页> 外文期刊>Basic & clinical pharmacology & toxicology. >Combination therapy of rosiglitazone, a peroxisome proliferator-activated receptor-gamma ligand, and NMDA receptor antagonist (MK-801) on experimental embolic stroke in rats.
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Combination therapy of rosiglitazone, a peroxisome proliferator-activated receptor-gamma ligand, and NMDA receptor antagonist (MK-801) on experimental embolic stroke in rats.

机译：罗格列酮，过氧化物酶体增殖物激活的受体-γ配体和NMDA受体拮抗剂（MK-801）联合治疗大鼠栓塞性中风。

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Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists have been found to have potent anti-inflammatory actions and suggested as potential therapies for brain ischaemia. Glutamate is the most common excitatory neurotransmitter in the central nervous system and is released excessively during ischaemia. Stroke therapy will require combinations of drug classes, because no single drug class has yet been proven efficacious in human beings. The present study was conducted to assess whether N-methyl-d-aspartate (NMDA) receptor antagonist (MK-801) treatment can improve recovery from ischaemic brain injury and whether rosiglitazone, a PPAR-gamma ligand, can increase its neuroprotective effect in an embolic model of stroke. Stroke was induced in rats by embolizing a preformed clot into the middle cerebral artery. Rosiglitazone (0.1 mg/kg, intraperitoneally) and MK-801 (0.1 mg/kg, intravenously) were injected immediately after embolization. Forty-eight hours later, the brains were removed, sectioned and stained with triphenyltetrazolum chloride and analysed by a commercial image processing software programme. Rosiglitazone and MK-801 alone or in combination decreased infarct volume by 49.16%, 50.26% and 81.32%, respectively (P < 0.001). Moreover, the combination therapy significantly decreased the infarct volume when compared to any drug used alone (P < 0.05). MK-801 reduced the brain oedema by 68% compared to the control group (P < 0.05), but rosiglitazone or combination did not show any significant effect. The drugs alone or in combination also demonstrated improved neurological function, but combination therapy was more effective on neurological deficits improving. Our data show that the combination of MK-801 and rosiglitazone is more neuroprotective in thromboembolic stroke than given alone; this effect perhaps represents a possible additive effect in the brain infarction.
机译：已发现过氧化物酶体增殖物激活的受体-γ（PPAR-γ）激动剂具有有效的抗炎作用，并被建议作为脑缺血的潜在疗法。谷氨酸是中枢神经系统中最常见的兴奋性神经递质，在缺血时会过度释放。中风疗法将需要药物类别的组合，因为还没有一种药物类别被证明对人类有效。本研究旨在评估N-甲基-d-天冬氨酸（NMDA）受体拮抗剂（MK-801）的治疗是否可以改善缺血性脑损伤的恢复，以及PPAR-γ配体罗格列酮是否可以增强其对神经元的保护作用。中风栓塞模型。通过将预先形成的血栓栓塞入大脑中动脉，在大鼠中诱发中风。栓塞后立即注射罗格列酮（0.1 mg / kg，腹膜内）和MK-801（0.1 mg / kg，静脉内）。 48小时后，取出大脑，切成薄片并用三苯基四唑氯化物染色，并通过商业图像处理软件程序进行分析。罗格列酮和MK-801单独或联合使用可分别减少49.16％，50.26％和81.32％的梗塞体积（P <0.001）。此外，与任何单独使用的药物相比，联合疗法显着减少了梗塞体积（P <0.05）。与对照组相比，MK-801减轻了脑水肿68％（P <0.05），但罗格列酮或罗格列酮未显示任何明显的作用。单独或联合用药也表现出改善的神经功能，但联合治疗对改善神经功能缺损更有效。我们的数据显示，MK-801和罗格列酮的组合对血栓栓塞性中风的神经保护作用大于单独给予。这种作用可能代表了在脑梗塞中可能的累加作用。

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