高尿酸血症促进大鼠海马组织中β-淀粉样蛋白沉积的机制研究

目的： 观察血清尿酸水平对大鼠认知功能和海马组织中β-淀粉样蛋白（β-amyloid，Aβ）表达的影响，并探讨其相关机制。方法： 将24只雄性Wistar大鼠随机分为对照组、低剂量模型组、中剂量模型组和高剂量模型组，每组6只，后3组采用酵母膏饲料喂养联合不同浓度氧嗪酸钾腹腔注射的方法制备高尿酸血症动物模型，共4周。通过Morris水迷宫检测各组大鼠学习记忆能力；通过ELISA和蛋白免疫印迹法检测各组大鼠海马组织中Aβ及Aβ生成和清除途径中关键蛋白的表达水平。结果： 与对照组相比，各模型组尿酸水平均明显升高（P<0.01）；4组大鼠穿越平台次数及在平台象限停留时间无明显差异。与对照组相比，各模型组大鼠海马组织中Aβ1 42、淀粉样肽前体蛋白（amyloid precursor protein，APP）、β-分泌酶1（β-site APP cleaving enzyme 1，BACE1）、中性肽链内切酶（neprilysin，NEP）、胰岛素降解酶（insulin degrading enzyme，IDE）表达均增加，且随血清尿酸水平的增加而升高；而ATP结合转运蛋白G超家族成员2（ATP-binding cassette transporter G2，ABCG2）表达则减少，且随血清尿酸水平的增加而逐渐降低。结论： 高尿酸血症能促进大鼠海马组织中Aβ沉积，可能通过APP-BACE1途径增加Aβ的生成或ABCG2途径减少Aβ清除，而不是通过NEP、IDE降解途径减少Aβ降解；高尿酸血症对大鼠认知功能无明显影响。

Hyperuricemia accelerate Aβ deposition in rat hippocampus and the related mechanisms#br#

Objective To investigate the effects of serum uric acid levels on cognitive function and Aβ expression in hippocampus of rats, and to explore the related mechanisms. Methods Twenty four Wistar male rats were randomly divided into control group, low dose model group, middle dose model group and high dose model group, with 6 rats in each group. The hyperuricemia animal model was established by using yeast extract feed combined with different concentrations of potassium oxonate intraperitoneal injection for 4 weeks. The learning and memory ability of the rats in each group was tested by Morris water maze. The expression levels of Aβ and key proteins in Aβ production and clearance pathways in the hippocampus of rats in each group were detected by ELLISA and Western blotting assays. Results Compared with the control group, the level of uric acid in each model group was significantly increased (P<0.01). And there was no significant difference in the number of times of crossing the platform and the time spent in the quadrant of the platform in each group. Compared with control group, the expression levels of Aβ1 42, amyloid precursor protein (APP), β site APP cleaving enzyme 1 (BACE1), neprilysin (NEP) and insulin degrading enzyme (IDE) were increased in model groups, and the expression levels increased with the raise of serum uric acid level. However, the expression of ABCG2 was decreased in model group, and gradually decreased with the increase of serum uric acid level. Conclusion Hyperuricemia can aggravate Aβ deposition in rat hippocampus, possibly through the APP BACE1 pathway to increase the production of Aβ or/and the ABCG2 pathway to reduce the clearance of Aβ, rather than through NEP, IDE degradation pathways. Hyperuricemia had no significant effect on cognitive function.