Diabetes:降糖药linagliptin可能减少中风后脑损伤
2013-05-06 mumu 生物谷
--在小鼠中开展的一项研究中,瑞典卡罗林斯卡医学院的科学家们发现了一种新的潜在疗法,可能减少2型糖尿病患者中风后的脑损伤。所建议的药物已获批准用于2型糖尿病的治疗。然而,科学家们希望,这一新的研究成果,也可能开辟了减少其他中风高风险患者中风发作后脑损伤的可能性。该项研究已在线发表于Diabetes期刊。 中风是当氧运输缺乏、血液凝块(血栓)或血管破裂导致大脑中部分神经组织的损伤。糖尿
--在小鼠中开展的一项研究中,瑞典卡罗林斯卡医学院的科学家们发现了一种新的潜在疗法,可能减少2型糖尿病患者中风后的脑损伤。所建议的药物已获批准用于2型糖尿病的治疗。然而,科学家们希望,这一新的研究成果,也可能开辟了减少其他中风高风险患者中风发作后脑损伤的可能性。该项研究已在线发表于Diabetes期刊。
中风是当氧运输缺乏、血液凝块(血栓)或血管破裂导致大脑中部分神经组织的损伤。糖尿病患者发生中风的风险比一般群体高。目前,常用于减少中风后果(伤残)的唯一急性期疗法是溶栓,在症状出现后迅速给药,溶解闭塞血管中的血液凝块。
然而,这种疗法仅适合于10%的中风患者,同时具有潜在的严重副作用,主要是脑出血。此外,溶栓治疗的效果在糖尿病患者中会降低,这是因为糖尿病本身可导致一种敏感的血管结构。
该项研究的基础是一种化学物质,名为linagliptin(商品名为Trajenta),该药已商业化用于糖尿病的治疗。结合运动及特殊饮食,linagliptin能够降低2型糖尿病患者的血糖水平。在这项研究中,在诱导中风试验前后,科学家们将linagliptin或安慰剂给药糖尿病小鼠。通过采用该研究的设计,科学家模拟了2型糖尿病患者接受linagliptin治疗的情景。
结果表明,linagliptin能够激发神经保护,同时在很大程度上减少中风后脑损伤,这种作用独立于该药的降糖效果。这反过来表明,2型糖尿病患者中,当给与linagliptin治疗,在中风后可能比接受其他药物具有更好的预后。
Linagliptin是一种二肽基肽酶–4(DPP-4)抑制剂,是勃林格殷格翰(Boehringer Ingelheim )的原研产品,已获美国、欧盟、日本、印度等国批准,作为2型糖尿病患者饮食和运动治疗的一种辅助治疗,用以改善血糖控制。
编译自:Diabetes drug may reduce brain damage after stroke
doi:10.2337/db12-0988
PMC:
PMID:
The DPP-4 Inhibitor Linagliptin Counteracts Stroke in the Normal and Diabetic Mouse Brain A Comparison With Glimepiride
Vladimer Darsalia, Henrik Orts?ter, Anna Olverling, et al
Abstract:Type 2 diabetes is a strong risk factor for stroke. Linagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor in clinical use against type 2 diabetes. The aim of this study was to determine the potential antistroke efficacy of linagliptin in type 2 diabetic mice. To understand whether efficacy was mediated by glycemia regulation, a comparison with the sulfonylurea glimepiride was done. To determine whether linagliptin-mediated efficacy was dependent on a diabetic background, experiments in nondiabetic mice were performed. Type 2 diabetes was induced by feeding the mice a high-fat diet for 32 weeks. Mice were treated with linagliptin/glimepiride for 7 weeks. Stroke was induced at 4 weeks into the treatment by transient middle cerebral artery occlusion. Blood DPP-4 activity, glucagon-like peptide-1 (GLP-1) levels, glucose, body weight, and food intake were assessed throughout the experiments. Ischemic brain damage was measured by determining stroke volume and by stereologic quantifications of surviving neurons in the striatum/cortex. We show pronounced antistroke efficacy of linagliptin in type 2 diabetic and normal mice, whereas glimepiride proved efficacious against stroke in normal mice only. These results indicate a linagliptin-mediated neuroprotection that is glucose-independent and likely involves GLP-1. The findings may provide an impetus for the development of DPP-4 inhibitors for the prevention and treatment of stroke in diabetic patients.
作者:mumu
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