Effects of Etanercept against Transient Cerebral Ischemia in Diabetic Rats.
Effects of Etanercept against Transient Cerebral Ischemia in Diabetic Rats.
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DOI：
10.1155/2015/189292
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发表时间：
2015
影响因子：
--
通讯作者：
Hibino Y
中科院分区：
文献类型：
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作者：
Iwata N;Takayama H;Xuan M;Kamiuchi S;Matsuzaki H;Okazaki M;Hibino Y
已知糖尿病可加重急性脑缺血性损伤。以往的研究表明，糖尿病大鼠短暂性脑缺血引起的梗死体积大于非糖尿病大鼠。肿瘤坏死因子-α（TNF-α）是脑缺血时产生的一种促炎蛋白，可促进细胞凋亡。依那西普（ETN）是一种重组TNF受体（p75）-Fc融合蛋白，竞争性抑制TNF-α。因此，我们评估了慢性或急性治疗与ETN对大脑中动脉闭塞/再灌注（MCAO/Re）造成的脑损伤的神经保护作用与链脲佐菌素诱导的糖尿病大鼠。此外，我们还观察了ETN对细胞凋亡和髓过氧化物酶活性的影响。在MCAO前单次给予ETN显著抑制非糖尿病大鼠脑损伤的加重，通过梗死体积评估。与此相反，糖尿病状态明显加重MCAO/再诱导的脑损伤，尽管ETN治疗前24小时内MCAO。在糖尿病大鼠模型中，ETN以900 μg/kg/d重复给药，可改善糖尿病大鼠的神经功能损害。结果提示，反复应用ETN可预防糖尿病状态下脑缺血损伤的加重，其作用机制主要是抗炎作用。
Diabetes mellitus is known to exacerbate acute cerebral ischemic injury. Previous studies have demonstrated that infarction volumes caused by transient cerebral ischemia were greater in diabetic rats than in nondiabetic rats. Tumor necrosis factor-α (TNF-α) is a proinflammatory protein produced in the brain in response to cerebral ischemia that promotes apoptosis. Etanercept (ETN), a recombinant TNF receptor (p75)-Fc fusion protein, competitively inhibits TNF-α. Therefore, we evaluated the neuroprotective effects of chronic or acute treatment with ETN on cerebral injury caused by middle cerebral artery occlusion/reperfusion (MCAO/Re) in rats with streptozotocin-induced diabetes. Furthermore, we evaluated the effects of ETN against the apoptosis and myeloperoxidase activity. Single administration of ETN before MCAO significantly suppressed exacerbation of cerebral damage in nondiabetic rats, as assessed by infarct volume. In contrast, the diabetic state markedly aggravated MCAO/Re-induced cerebral damage despite ETN treatment within 24 h before MCAO. However, the damage was improved by repeated administration of ETN at 900 μg/kg/daily in rats in an induced diabetic state. These results suggested that repeated administration of ETN can prevent exacerbation of cerebral ischemic injury in the diabetic state and is mainly attributed to anti-inflammatory effects.