维生素A缺乏对APP/PS1小鼠认知功能和补体系统的影响

目的 研究维生素A缺乏(vitamin A deficiency, VAD)对阿尔茨海默症(Alzheimer''s disease, AD)模型APP/PS1小鼠认知功能和补体系统的影响，探索补体因子影响APP/PS1小鼠认知功能的作用机制。方法 将20只雄性APP/PS1小鼠随机分为维生素A缺乏组(VAD)和维生素A正常组(vitamin A normal, VAN)，进行45周的特殊饲料干预。45周后，进行新物体识别实验和Y迷宫实验以检测小鼠的认知功能，采用免疫组化和Western blot检测小鼠皮质中的补体系统起始因子C1q的蛋白表达情况，采用实时荧光定量PCR(real-time quantitative polymerase chain reaction, RT-qPCR)检测小鼠海马中C1q以及其他补体因子的mRNA表达情况。结果 新物体识别实验和Y迷宫实验的结果显示，维生素A缺乏使APP/PS1小鼠认知功能障碍加重。免疫组化和Western blot的结果显示，与VAN组相比，VAD干预45周后皮质中的C1q的蛋白表达量显著升高(P＜0.05)。RT-qPCR结果显示，VAD干预45周后，海马中C1q和C1r的mRNA表达显著上调(P＜0.05)，C4、C4BP和C5的mRNA表达显著下调(P＜0.05)，而C1s、C2、C3和C5aR1的mRNA表达无明显变化。结论 长期缺乏维生素A会加重AD模型APP/PS1小鼠的认知功能障碍并影响大脑中的补体系统，且补体因子可能参与VAD影响认知功能的作用机制。

Effects of vitamin A deficiency on cognitive function and complement system in APP/PS1 mice

Objective To identify the effect of vitamin A deficiency (VAD) on the cognitive function and complement system of APP/PS1 mice, and explore the mechanism of the complement factors on the cognitive function of APP/PS1 mice. Methods Twenty male APP/PS1 mice were randomly divided into two groups (VAD and VAN) for 45 weeks of special feed intervention. After 45 weeks, new object recognition tasks and Y-maze tasks were performed to examine the cognitive function. The protein expression of C1q in the mouse cortex, the complement system initiation factor, was detected by Immunohistochemistry and Western blot. The mRNA expression of C1q and other complement factors in the hippocampus were detected by real-time quantitative polymerase chain reaction(RT-qPCR). Results The behavioral experiments showed that vitamin A deficiency exacerbated the cognitive dysfunction in the APP/PS1 mice. Immunohistochemistry and Western blot indicated that the protein expression of C1q in the cortex was significantly increased after 45 weeks of the VAD diet (P<0.05). RT-qPCR results illustrated that the mRNA expressions of C1q and C1r in the hippocampus were significantly upregulated (P<0.05), and the mRNA expressions of C4, C4BP, and C5 were significantly downregulated (P<0.05), while the mRNA expressions of C1s, C2, C3, and C5aR1 did not change significantly. Conclusion Long-term vitamin A deficiency aggravates the cognitive dysfunction and influences the complement system in APP/PS1 mice, and the complement factors may be involved in the mechanism of VAD influencing cognitive function.