School of Public Health, Southwest Medical University, Luzhou, 646000, China.
Clinical Drug Trial Institution, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.
Sci Rep. 2021 Mar 24;11(1):6732. doi: 10.1038/s41598-021-86279-y.
Uric acid is a powerful antioxidant. However, its elevated levels in association with cardiovascular diseases predispose individuals to cognitive impairment. Uric acid's effects on cognition may be related to its concentration and exposure period. We aimed to explore the effects of long-term elevated serum uric acid on cognitive function and hippocampus. Rats were randomly divided into four groups: NC, M1, M2 and M3 groups. Hyperuricemia was established in rats at week 6 and maintained until week 48 in groups M1, M2 and M3. The rats' spatial learning and memory abilities were assessed by the Morris Water Maze test at weeks 0, 6, 16, 32, and 48. After week 48, we observed pathological changes in right hippocampal CA1 and CA3 regions, and measured levels of oxidative stress, inflammatory cytokines, and β-amyloid peptide of left hippocampus. Starting from week 6, the serum uric acid level of M3 group > M2 group, the serum uric acid level of M2 group > M1 group, and the serum uric acid level of M1 group > NC group. The rats in M3 and M2 groups had longer escape latencies, longer mean distances to the platform, more extensive pathological damage, stronger inflammation response, higher oxidative stress and β-amyloid peptide levels than those in NC group. No significant differences were observed between M1 and NC groups. In addition, we also found that oxidative stress significantly correlated with tumour necrosis factor-α and β-amyloid peptide. Long-term elevated serum uric acid was significantly associated with cognitive impairment risk. Oxidative stress, tumour necrosis factor-α and β-amyloid peptide may mediate the pathogenesis of the cognitive impairment induced by uric acid. The detrimental effect of elevated serum uric acid on cognitive function was probably expressed when the serum uric acid concentration reached a certain level.
尿酸是一种强大的抗氧化剂。然而，其在心血管疾病中的升高水平使个体易发生认知障碍。尿酸对认知的影响可能与其浓度和暴露时间有关。我们旨在探讨长期高血清尿酸对认知功能和海马体的影响。大鼠随机分为四组：NC、M1、M2 和 M3 组。M1、M2 和 M3 组在第 6 周建立高尿酸血症，并维持至第 48 周。在第 0、6、16、32 和 48 周时，通过 Morris 水迷宫测试评估大鼠的空间学习和记忆能力。第 48 周后，观察右海马 CA1 和 CA3 区的病理变化，并测量左海马的氧化应激、炎症细胞因子和 β-淀粉样肽水平。从第 6 周开始，M3 组的血清尿酸水平>M2 组，M2 组的血清尿酸水平>M1 组，M1 组的血清尿酸水平>NC 组。M3 和 M2 组的大鼠逃避潜伏期较长，到达平台的平均距离较长，病理损伤较广泛，炎症反应较强，氧化应激和 β-淀粉样肽水平较高，与 NC 组相比差异有统计学意义。M1 组与 NC 组之间无显著差异。此外，我们还发现氧化应激与肿瘤坏死因子-α和 β-淀粉样肽显著相关。长期高血清尿酸与认知障碍风险显著相关。氧化应激、肿瘤坏死因子-α和 β-淀粉样肽可能介导尿酸引起的认知障碍的发病机制。当血清尿酸浓度达到一定水平时，高血清尿酸对认知功能的有害影响可能表现出来。
