目的 探究姜黄素对Aβ_25-35诱导痴呆模型大鼠认知功能及学习记忆能力的影响，并分析其与5/12/15-脂氧合酶（5/12/15-LOX）通路的关联性。方法 将SD大鼠随机分为对照组、模型组、姜黄素（50、200 mg/kg）组、多奈哌齐组。采用mNSS评分、新型物体识别以及Y迷宫任务测试评估神经功能与认知行为；尼氏和HE染色评估海马神经元病理变化；ELISA检测海马组织β-淀粉样蛋白（Aβ）₄₂、Aβ₄₀、p-tau、t-tau、神经丝轻链蛋白（NFL）及脂氧合酶（LOXs）通路代谢产物[5-羟二十碳四烯酸（5-HETE）、12-HETE、15-HETE、白三烯B4（LTB4）]水平；RT-qPCR和Western blotting检测海马组织5-LOX、12-LOX、15-LOX的表达。结果 与模型组比较，姜黄素（50、200 mg/kg）组mNSS评分、病理损伤评分、Aβ₄₂/Aβ₄₀、p-tau/t-tau以及NFL、5-HETE、12-HETE、15-HETE、LTB4含量均显著降低，5-LOX、12-LOX、15-LOX的mRNA及蛋白表达显著降低，识别指数、自发交替率、正常神经元数量显著升高（P＜0.05），且呈剂量相关性。结论 姜黄素改善Aβ_25-35诱导痴呆模型大鼠认知功能，其效应与抑制5/12/15-LOX通路活性相关。

Objective To investigate the effects of curcumin on cognitive function and learning and memory in Aβ_25-35-induced dementia model rats, and to analyze its association with the 5/12/15-LOX pathway. Methods SD rats were randomly divided into control group, model group, curcumin (50, 200 mg/kg) group, and donepezil group. The mNSS score, novel object recognition, and Y-maze task tests were used to evaluate neurological function and cognitive behaviors. Nissl and HE stainings were used to evaluate the pathological changes of hippocampal neurons. ELISA was used to detect the levels of Aβ₄₂, Aβ₄₀, p-tau, t-tau, NFL and the metabolic products of LOXs pathways (5-HETE, 12-HETE, 15-HETE, LTB4) in the hippocampal tissue. RT-qPCR and Western blotting were used to detect the expression levels of 5-LOX, 12-LOX and 15-LOX in the hippocampal tissue. Results Compared with the model group, the mNSS score, pathological injury score, Aβ₄₂/Aβ₄₀, p-tau/t-tau, the NFL, 5-HETE, 12-HETE, 15-HETE, and LTB4 contents in the curcumin group were decreased, while the mRNA and protein expressions of 5-LOX, 12-LOX, and 15-LOX were decreased, and the recognition index, spontaneous alternation rate, and the number of normal neurons were increased (P < 0.05), and it shows a dose-dependent relationship. Conclusion Curcumin improves cognitive function in Aβ_25-35-induced dementia model rats, and its effects are associated with the inhibition of 5/12/15-LOX pathway activity.

R286.1

河北省医学科学研究课题计划资助项目（20260789）