Shao Ju-Wei, Wang Jin-De, He Qian, Yang Ying, Zou Ying-Ying, Su Wei, Xiang Shu-Tian, Li Jian-Bo, Fang Jing
Department of Radiology, The Second People's Hospital of Yunnan Province, The Affiliated Hospital of Yunnan University, Kunming 650021, Yunnan Province, China.
College of Clinical Medicine, Kunming Medical University, Kunming 650500, Yunnan Province, China.
World J Diabetes. 2021 Apr 15;12(4):499-513. doi: 10.4239/wjd.v12.i4.499.
Type 2 diabetes mellitus (T2DM) has been strongly associated with an increased risk of developing cognitive dysfunction and dementia. The mechanisms of diabetes-associated cognitive dysfunction (DACD) have not been fully elucidated to date. Some studies proved lower cerebral blood flow (CBF) in the hippocampus was associated with poor executive function and memory in T2DM. Increasing evidence showed that diabetes leads to abnormal vascular endothelial growth factor (VEGF) expression and CBF changes in humans and animal models. In this study, we hypothesized that DACD was correlated with CBF alteration as measured by three-dimensional (3D) arterial spin labeling (3D-ASL) and VEGF expression in the hippocampus.
To assess the correlation between CBF (measured by 3D-ASL and VEGF expression) and DACD in a rat model of T2DM.
Forty Sprague-Dawley male rats were divided into control and T2DM groups. The T2DM group was established by feeding rats a high-fat diet and glucose to induce impaired glucose tolerance and then injecting them with streptozotocin to induce T2DM. Cognitive function was assessed using the Morris water maze experiment. The CBF changes were measured by 3D-ASL magnetic resonance imaging. VEGF expression was determined using immunofluorescence.
The escape latency time significantly reduced 15 wk after streptozotocin injection in the T2DM group. The total distance traveled was longer in the T2DM group; also, the platform was crossed fewer times. The percentage of distance in the target zone significantly decreased. CBF decreased in the bilateral hippocampus in the T2DM group. No difference was found between the right CBF value and the left CBF value in the T2DM group. The VEGF expression level in the hippocampus was lower in the T2DM group and correlated with the CBF value. The escape latency negatively correlated with the CBF value. The number of rats crossing the platform positively correlated with the CBF value.
Low CBF in the hippocampus and decreased VEGF expression might be crucial in DACD. CBF measured by 3D-ASL might serve as a noninvasive imaging biomarker for cognitive impairment associated with T2DM.
2型糖尿病（T2DM）与发生认知功能障碍和痴呆的风险增加密切相关。糖尿病相关认知功能障碍（DACD）的机制迄今尚未完全阐明。一些研究证明，海马体中脑血流量（CBF）降低与T2DM患者的执行功能和记忆力差有关。越来越多的证据表明，糖尿病会导致人类和动物模型中血管内皮生长因子（VEGF）表达异常和CBF变化。在本研究中，我们假设DACD与通过三维（3D）动脉自旋标记（3D-ASL）测量的CBF改变以及海马体中的VEGF表达相关。
评估T2DM大鼠模型中CBF（通过3D-ASL测量）和VEGF表达与DACD之间的相关性。
将40只雄性Sprague-Dawley大鼠分为对照组和T2DM组。通过给大鼠喂食高脂饮食和葡萄糖以诱导糖耐量受损，然后注射链脲佐菌素诱导T2DM，建立T2DM组。使用莫里斯水迷宫实验评估认知功能。通过3D-ASL磁共振成像测量CBF变化。使用免疫荧光法测定VEGF表达。
T2DM组在注射链脲佐菌素15周后逃避潜伏期显著缩短。T2DM组的总游动距离更长；此外，穿过平台的次数更少。目标区域内的距离百分比显著降低。T2DM组双侧海马体的CBF降低。T2DM组右侧CBF值与左侧CBF值之间未发现差异。T2DM组海马体中的VEGF表达水平较低，且与CBF值相关。逃避潜伏期与CBF值呈负相关。穿过平台的大鼠数量与CBF值呈正相关。
海马体中低CBF和VEGF表达降低可能在DACD中起关键作用。通过3D-ASL测量的CBF可能作为T2DM相关认知障碍的非侵入性成像生物标志物。
