摘要
背景：糖原合酶激酶（GSK）-3β和脑源性神经营养因子（BDNF）在轻度认知障碍（MCI）和2型糖尿病（T2DM）中起着至关重要的作用。潜在的机制可能涉及炎症和氧化应激。 目的：探讨老年T2DM患者中GSK-3β/ BDNF比值与MCI的相关性，以及GSK-3β/ BDNF比值是否可作为M2并发T2DM（MD）的新诊断生物标志物。 方法：根据认知水平和GSK-3β/ BDNF比值四分位数对326例中国老年T2DM患者进行分类。根据国家老年痴呆协会协会工作组标准诊断出MCI。除常规血尿和生化检查外，还使用蒙特利尔认知评估量表（MoCA）评估认知功能，并使用ELISA方法测量GSK-3β活性和血清BDNF，白介素1β（IL-1β）的水平，高迁移率族box-1（HMGB1）蛋白，丙二醛（MDA）和8-isoprostaglandinF2α（8-iso-PGF2α）。 结果：我们发现GSK-3β活性与BDNF呈负相关（r = -0.270，P = 0.008），而GSK-3β/ BDNF比值较高的患者的MoCA评分较低（P = 0.001）。与没有MCI（nMD）的T2DM患者相比，MD患者的GSK-3β活性和GSK-3β/ BDNF比率更高，但BDNF水平较低。至于炎症和氧化应激，IL-1β与GSK-3β活性呈负相关，而8-isoPGF2α与GSK-3β活性和GSK-3β/ BDNF比值呈正相关。当GSK-3β/ BDNF比值四分位数从最低值升高到最高值时，MCI的优势比逐渐增加（6.90，95％CI 3.22-14.78）。相反，MoCA评分与GSK-3β/ BDNF比，年龄和快速血糖（FBG）相关，其中GSK-3β/ BDNF比对认知的影响最大（β= -0.199，P <0.001）。 结论：我们的数据提供了GSK-3β/ BDNF比值与MCI之间密切联系的证据。与单独使用GSK-3β或BDNF相比，GSK-3β/ BDNF比率可以作为更好的MD诊断生物标志物，并且增加的GSK-3β/ BDNF比率表明认知功能较差。
关键词: 轻度认知障碍，2型糖尿病，糖原合成酶激酶-3β，脑源性神经营养因子，炎症，氧化应激。
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