南方医科大学学报

南方医科大学学报 ›› 2026, Vol. 46 ›› Issue (10): 2447-2455.doi: 10.12122/j.issn.1673-4254.2026.10.14

• • 上一篇    

酸枣仁汤调控Hippo-YAP通路抑制神经炎症改善APP/PS1模型小鼠海马神经元损伤

牛绮萱1(), 吴丹1, 赖碧璇1, 陈俊华1, 王政喻1, 龙清华1,2()   

  1. 1.湖北民族大学，医学部，湖北 恩施 445000
    2.湖北民族大学，风湿性疾病发生与干预湖北省重点实验室，湖北 恩施 445000
  • 收稿日期:2026-03-30 出版日期:2026-10-20 发布日期:2026-10-26
  • 通讯作者: 龙清华 E-mail:2868113586@qq.com;287201413@qq.com
  • 作者简介:牛绮萱，在读硕士研究生，E-mail: 2868113586@qq.com
  • 基金资助:
    国家自然科学基金青年科学基金(82204964);中国博士后科学基金(2025M773957);湖北省中医药管理局中医药科研面上项目(ZY2025M001);中华中医药学会青年人才托举工程项目(2025-QNRC2-B09);湖北省教育厅科学研究计划重点项目(D20251902)

Suanzaoren Decoction inhibits neuroinflammation and alleviates hippocampal neuronal injury in APP/PS1 transgenic mice by regulating the Hippo-YAP pathway

Qixuan NIU1(), Dan WU1, Bixuan LAI1, Junhua CHEN1, Zhengyu WANG1, Qinghua LONG1,2()   

  1. 1.Health Medical Center, Hubei Minzu University, Enshi 445000, China
    2.Hubei Provincial Key Laboratory of Occurrence and Intervention of Rheumatic Diseases, Hubei Minzu University, Enshi 445000, China
  • Received:2026-03-30 Online:2026-10-20 Published:2026-10-26
  • Contact: Qinghua LONG E-mail:2868113586@qq.com;287201413@qq.com
  • Supported by:
    Natural Science Foundation for the Youth of China(82204964)

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摘要：

目的 探讨酸枣仁汤（SZRD）通过Hippo-YAP信号通路抑制神经炎症从而改善APP/PS1小鼠海马神经元损伤的机制。 方法 将30只7月龄APP/PS1小鼠随机分为APP/PS1模型组、酸枣仁汤低剂量组（12.96 g/kg）和酸枣仁汤高剂量组（25.92 g/kg），10只/组。另取10只7月龄雄性C57BL/6J小鼠用作空白组。给药组连续灌胃相应剂量酸枣仁汤，空白组与APP/PS1模型组灌胃等体积生理盐水，持续28 d。灌胃结束后，利用Morris水迷宫实验评估小鼠学习记忆能力；尼氏染色检测神经元的数量；硫磺素S染色观察β-淀粉样蛋白（Aβ）斑块的沉积情况；免疫组化观察小鼠海马区小胶质细胞标志物离子钙结合衔接分子1（IBA1）的表达情况；IBA1/Aβ免疫荧光双标染色检测海马IBA1与Aβ的表达情况；通过RNA测序筛选关键靶点；Western blotting法检测小鼠海马组织中Hippo-YAP通路蛋白哺乳动物STE20样蛋白激酶1（MST1）、大肿瘤抑制因子1（LATS1）、Yes相关蛋白（YAP1）、磷酸化Yes相关蛋白（p-YAP1-s127）及神经炎症相关蛋白核因子‑κB（NF‑κB p65）、磷酸化NF‑κB p65（p-NF‑κB p65-ser536）、白细胞介素（IL）-6、IL-1β、肿瘤坏死因子-α（TNF-α）的表达水平。 结果 动物实验显示，与APP/PS1模型组相比，低、高剂量酸枣仁汤组小鼠学习记忆水平提高（P<0.05）；神经元排列更整齐，数量增加（P<0.05）；Aβ沉积减少（P<0.05）；IBA1表达水平降低（P<0.05）；IBA1阳性面积、Aβ阳性面积以及IBA1/Aβ共定位程度均降低（P<0.05）；RNA测序结果显示，酸枣仁汤可下调Hippo通路关键基因与炎症相关的基因；Western blotting结果显示，与APP/PS1模型组相比，海马组织中，MST1、LATS1、p-YAP1-s127/YAP1、p‑NF‑κB p65-ser536/ NF‑κB p65、IL-1β、IL-6、TNF-α蛋白表达降低（P<0.05）。 结论 酸枣仁汤可通过调控Hippo-YAP通路抑制神经炎症改善APP/PS1模型小鼠海马神经元损伤。

关键词: 酸枣仁汤, APP/PS1小鼠, RNA测序, Hippo-YAP信号通路, 神经炎症

Abstract:

Objective To investigate the mechanism by which Suanzaoren Decoction (SZRD) ameliorates hippocampal neuronal injury in APP/PS1 mice. Methods Thirty 7-month-old APP/PS1 transgenic mice were randomized into 3 groups for daily gavage with saline or SZRD at 12.96 or 25.92 g/kg (n=10) for 28 consecutive days, with 10 saline-treated age-matched male C57BL/6J mice as the blank control group. Spatial learning and memory abilities of the mice were evaluated using Morris water maze test. Neuronal integrity and amyloid β (Aβ) deposition were examined with Nissl staining and Thioflavin S staining, respectively, and hippocampal IBA1 expression was detected by immunohistochemistry. IBA1/Aβ immunofluorescence double staining was used to evaluate the spatial relationship between hippocampal microglia and Aβ plaques. RNA sequencing was employed to identify the key targets. Western blotting was performed to detect hippocampal expressions of nuclear factor kappa-B (NF‑κB p65), p-NF‑κB p65-ser536, interleukin (IL)-6, IL-1β, tumor necrosis factor-α (TNF-α), and the Hippo-YAP pathway proteins including mammalian sterile 20-like kinase 1 (MST1), large tumor suppressor 1 (LATS1), Yes-associated protein (YAP1), and p-YAP1- s127. Results In APP/PS1 mice, SZRD at both the low and high doses significantly improved learning and memory performance and neuronal organization, increased hippocampal neuronal number, and reduced amyloid-β (Aβ) deposition and IBA1 expression. The treatments also significantly decreased IBA1-positive area, Aβ-positive area, and IBA1/Aβ co-localization in the transgenic mice. RNA sequencing revealed that SZRD downregulated the key genes in the Hippo signaling pathway and inflammation-related genes in APP/PS1 mice. Western blotting demonstrated that SZRS treatment significantly lowered hippocampal expressions of MST1, LATS1, p-YAP1-s127/YAP1, p-NF-κB p65-Ser536/NF-κB p65, IL-1β, IL-6, and TNF-α in APP/PS1 mice. Conclusion SZRD ameliorates hippocampal neuronal injury in APP/PS1 mice by regulating the Hippo-YAP signaling pathway and inhibiting neuroinflammation.

Key words: Suanzaoren Decoction, APP/PS1 mice, RNA sequencing, hippo-YAP signaling pathway, neuroinflammation