Effects of HSYA on serum and brain cholesterol levels in AD rats based on quantitative proteomics
Effects of HSYA on serum and brain cholesterol levels in AD rats based on quantitative proteomics
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DOI：
10.1080/00207454.2022.2082964
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发表时间：
2022-05
影响因子：
2.2
通讯作者：
Chunhui Wang;Jiawei Hou;Mengyu Zhang;Yanjie Zheng;Hongxia Ye;Yanqiang Qi;Li Guo;Yan-li Hu
中科院分区：
文献类型：
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作者：
Chunhui Wang;Jiawei Hou;Mengyu Zhang;Yanjie Zheng;Hongxia Ye;Yanqiang Qi;Li Guo;Yan-li Hu
摘要背景：羟基红花黄A （hydroxyysafflor yellow A， HSYA）对阿尔茨海默病（Alzheimer 's disease， AD）大鼠有一定的改善作用，但具体机制尚不清楚。本研究旨在观察HSYA对a - β1-42诱导的AD大鼠学习记忆能力的调节作用。材料与方法：采用Morris水迷宫实验评价HSYA对AD模型大鼠学习记忆能力的影响。基于定量蛋白质组学研究HSYA治疗AD的有效靶点及可能的分子机制。结果：通过Morris水迷宫实验，我们发现HSYA治疗后，模型组大鼠的学习能力有明显提高。定量蛋白质组学结果显示，在“模型/假手术”对照组与“HSYA治疗/模型”对照组的11种常见差异蛋白中，胆固醇合成限速酶甲羟酸脱羧酶（Mvd） Western Blot结果与定量蛋白质组学分析结果一致。我们发现HSYA可以抑制AD大鼠海马组织中BACE蛋白的表达，降低a - β1-42的水平。此外，HSYA还能降低血清和海马的胆固醇水平。结论：综上所述，HSYA可有效改善AD大鼠的学习记忆障碍，并通过有效控制血清和脑胆固醇，下调BACE的表达，从而降低a - β1-42的含量，发挥神经保护作用。
Abstract Backgroud: Hydroxysafflor yellow A (HSYA) has a certain improvement effect on Alzheimer’s disease (AD) rats, but its specific mechanism is still unclear. The purpose of this study was to observe the regulatory effect of HSYA on learning and memory ability of AD rats induced by Aβ1-42. Materials and methods: Morris water maze test was used to evaluate the effect of HSYA on the learning and memory ability of AD model rats. To explore the effective targets and potential molecular mechanisms of HSYA in AD treatment based on quantitative proteomics. Results: Through the Morris water maze experiment, we found that after HSYA treatment, the learning ability of rats in the model group has been significantly improved. Quantitative proteomics results showed that among the 11 common differential proteins between the “model/sham operation” comparison group and the “HSYA treatment/model” comparison group, the cholesterol synthesis rate-limiting enzyme mevalonate decarboxylase (Mvd) Western Blot results are consistent with the results of quantitative proteomics analysis. We found that HSYA can inhibit the expression of BACE protein in hippocampus of AD rats and decrease the level of Aβ1-42. Besides, HSYA could also reduce cholesterol levels in serum and hippocampus. Conclusion: In summary, HSYA can effectively improve learning and memory disorders in AD rats, and exert neuroprotective effects by effectively controlling serum and brain cholesterol to down-regulate the expression of BACE and thus reduce the content of Aβ1-42.