目的  通过检测双氢青蒿素 (DHA)对5×FAD小鼠的认知行为，海马、大脑皮质和视网膜细胞形态、β-淀粉样蛋白（Aβ）及自噬相关蛋白的影响，来证实DHA影响AD的发病机制。 方法  选取5×FAD小鼠20只、野生型（WT）小鼠5只，均为雌性。随机将 5×FAD 小鼠分为模型（M）组、多奈哌齐（D）组、低剂量DHA（DHA-L）组和高剂量DHA（DHA-H）组。WT和M组小鼠不进行任何处理, D组给予多奈哌齐0.1 mg/（kg·d）；DHA-L组和DHA-H组分别给予DHA 10 mg/（kg·d）和20 mg/（kg·d）。D组、DHA-L组和DHA-H组每天灌胃1次，连用3个月。Morris实验测定其认知行为的变化；HE染色观察大脑皮质、海马和视网膜组织中神经细胞的排列和形态；免疫组织化学检测大脑皮质、海马和视网膜组织中Aβ蛋白的表达；Western blotting检测自噬相关蛋白（LC3-Ⅰ、LC3-Ⅱ、Beclin-1、P62、β-actin）表达。 结果  DHA-H组和D组更多地采用线性趋势探索路线。与M组比较，其他4组小鼠海马CA1、大脑皮质初级躯体感觉皮层S1 和视网膜中Aβ含量差异有统计学意义(P<0.0001)。DHA-L组、DHA-H组与M组间自噬相关蛋白表达差异均有统计学意义(P<0.01)。 结论  双氢青蒿素能改善阿尔茨海默病模型小鼠认知功能，改善神经细胞形态。可降低小鼠大脑皮层、海马和视网膜中Aβ的含量，改善自噬相关蛋白的沉积。

Objective To explore the pathogenesis of Alzheimer’s disease by examining the effects of dihydroartemisinin(DHA) on cognitive behavior, hippocampal, cerebral cortex and retinal cell morphology, β-amyloid(Aβ) and autophagy-related proteins in 5×FAD mice.   Methods  Twenty 5×FAD mice and 5 wild type (WT) mice were selected, all of which were female. The 5×FAD mice were randomly divided into model (M) group, donepezil (D) group, low-dose DHA (DHA-L) group, and high-dose DHA (DHA-H) group. The WT and M groups were not treated, and the D group was given donepezil 0.1 mg/kg per day. DHA-L group and DHA-H group were given 10 mg/kg and 20 mg/kg DHA per day, respectively. Group D, group DHA-L and group DHA-H were given intragastric administration once a day for 3 months. The changes of in cognitive behavior were measured by Morris experiment. HE staining was used to observe the arrangement and morphology of nerve cells in cerebral cortex, hippocampus and retina. The expressions of Aβ protein in cerebral cortex, hippocampus and retina were detected by immunohistochemistry. Western blotting detected the expression of autophagy related proteins (LC3-Ⅰ, LC3-Ⅱ, Beclin-1, P62, β-actin).   Results  The DHA-H group and the D group exhibited more frequent adoption of both linear and trending exploration routes. Compared to the model group, significant differences in the contents of Aβ  in the hippocampal CA1, cerebral cortex S1, and retinal were observed (P<0.0001) in the other four groups. The analysis also showed significant differences in autophagy-associated proteins between the DHA-L,  DHA-H, and model groups (P<0.01).  Conclusion  DHA improves cognitive function and increases the number of nerve cells in mice. It also reduces Aβ content in the cerebral cortex, hippocampus, and retina, along with improving autophagy-associated protein deposition in mice.