中国中药杂志

酸枣仁汤对APP/PS1模型小鼠海马神经元保护作用及PI3K/Akt信号通路的影响

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吴丹 ¹ , 赖碧璇 ¹ , 王政喻 ¹ , 牛绮萱 ¹ , 蔡元钦 ³ , 龙清华 ¹^,²^,^*

中国中药杂志 | 药理 2026,51(1): 173-180

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中国中药杂志 |药理 2026 , 51 (1) : 173 -180

酸枣仁汤对APP/PS1模型小鼠海马神经元保护作用及PI3K/Akt信号通路的影响

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吴丹¹, 赖碧璇¹, 王政喻¹, 牛绮萱¹, 蔡元钦³, 龙清华¹^,²^,^*

作者信息

^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

^3．云南中医药大学，云南昆明 650000

通讯作者:

龙清华，E-mail: 287201413@qq.com

Protective effects of Suanzaoren Decoction on hippocampal neuron and its influence on PI3K/Akt signaling pathway in APP/PS1 transgenic mice

Dan WU¹, Bi-xuan LAI¹, Zheng-yu WANG¹, Qi-xuan NIU¹, Yuan-qin CAI³, Qing-hua LONG¹^,²^,^*

Affiliations

^1.Medical School, Hubei Minzu University, Enshi 445000, China

^2.Hubei Provincial Key Laboratory of Occurrence and Intervention of Rheumatic Diseases, Hubei Minzu University, Enshi 445000, China

^3.Yunnan University of Chinese Medicine, Kunming 650000, China

出版时间: 2026-01-01 doi: 10.19540/j.cnki.cjcmm.20250930.701

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摘要

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探讨酸枣仁汤（SZRD）通过磷脂酰肌醇3-激酶（PI3K）/蛋白激酶B（Akt）信号通路抑制B细胞淋巴瘤-2（Bcl-2）相关X蛋白（Bax）/Bcl-2／半胱氨酸天冬氨酸蛋白酶-3（caspase-3）介导的细胞凋亡从而改善APP/PS1小鼠海马神经元损伤的机制。使用GEO数据库筛选阿尔茨海默病差异表达基因（DEGs），利用R语言对DEGs进行KEGG和GO富集分析。将30只6月龄APP/PS1模型小鼠随机分为APP/PS1组、酸枣仁汤低剂量组（12.96 g·kg^-1）和酸枣仁汤高剂量组（25.92 g·kg^-1），10只6月龄雄性C57BL/6J小鼠作为空白组。给药组分别给予相应药物灌胃，持续28 d。灌胃结束后，利用Morris水迷宫检测小鼠的学习记忆能力；尼氏染色检测神经元的数量；免疫组化检测海马神经元标志物特异性核蛋白（NeuN）的数量和海马神经元Aβ沉积情况；Western blot法检测小鼠海马组织中PI3K/Akt通路蛋白及凋亡相关蛋白Bcl-2、Bax、剪切的caspase-3（cleaved-caspase-3）、caspase-3的表达水平。结果显示，差异基因分析筛选出686个DEGs，GO富集分析显示其与突触功能、神经递质等生物学过程相关；KEGG富集分析主要涉及神经活性、PI3K/Akt等信号通路。动物实验显示，与APP/PS1组相比，酸枣仁汤低剂量组、酸枣仁汤高剂量组小鼠学习记忆水平显著提高，神经元数量显著增加，Aβ沉积显著减少，海马组织中p-PI3K/PI3K、p-Akt/Akt、Bcl-2蛋白表达均明显上升，Bax、cleaved-caspase-3/caspase-3蛋白表达均显著下降。综上所述，酸枣仁汤可能通过PI3K/Akt信号通路调控Bax/Bcl-2/caspase-3介导的细胞凋亡，从而改善APP/PS1小鼠海马神经元损伤，提高其认知水平。

关键词

酸枣仁汤 / APP/PS1小鼠 / PI3K/Akt通路 / 神经元凋亡

Abstract

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This study explored the mechanism by which Suanzaoren Decoction (SZRD) ameliorates hippocampal neuronal damage in APP/PS1 mice by inhibiting Bax/Bcl-2/caspase-3-mediated apoptosis through the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. Differentially expressed genes (DEGs) in Alzheimer's disease (AD) were screened using the GEO database, and KEGG and GO enrichment analyses were performed using R software. Thirty 6-month-old APP/PS1 transgenic mice were randomly assigned to three groups: APP/PS1 group, low-dose SZRD group (12.96 g·kg^-1), and high-dose SZRD group (25.92 g·kg^-1), while ten age-matched male C57BL/6J mice served as the blank control group. The treatment groups received SZRD by gavage for 28 consecutive days. Following treatment, spatial learning and memory were assessed using the Morris water maze test. Neuronal numbers were evaluated by Nissl staining. Immunohistochemistry (IHC) was used to detect neuron-specific nuclear protein (NeuN) and assess amyloid-β (Aβ) deposition in hippocampal neurons. Western blot was performed to measure the expression levels of PI3K/Akt pathway proteins and apoptosis-related markers, including Bcl-2, Bax, caspase-3, and cleaved-caspase-3 in hippocampal tissues. Bioinformatics analysis identified 686 DEGs, with GO enrichment linked to synaptic function and neurotransmitter transport, and KEGG pathways including neuroactive ligand-receptor interaction and PI3K/Akt signaling. In vivo experiments showed that, compared with APP/PS1 mice, both low-and high-dose SZRD groups exhibited improved learning and memory, increased neuronal numbers, and decreased Aβ deposition. Furthermore, hippocampal levels of p-PI3K/PI3K, p-Akt/Akt, and Bcl-2 were upregulated, while Bax and cleaved-caspase-3/caspase-3 levels were downregulated. In conclusion, SZRD may improve hippocampal neuronal damage and cognitive function in APP/PS1 mice by regulating Bax/Bcl-2/caspase-3-mediated apoptosis through the PI3K/Akt signaling pathway.

Key words

Suanzaoren Decoction / APP/PS1 mice / PI3K/Akt pathway / neuronal apoptosis

引用本文

吴丹, 赖碧璇, 王政喻, 牛绮萱, 蔡元钦, 龙清华. 酸枣仁汤对APP/PS1模型小鼠海马神经元保护作用及PI3K/Akt信号通路的影响. 中国中药杂志, 2026 , 51 (1) : 173 -180 . DOI: 10.19540/j.cnki.cjcmm.20250930.701

Dan WU, Bi-xuan LAI, Zheng-yu WANG, Qi-xuan NIU, Yuan-qin CAI, Qing-hua LONG. Protective effects of Suanzaoren Decoction on hippocampal neuron and its influence on PI3K/Akt signaling pathway in APP/PS1 transgenic mice[J]. Chinese Journal of Traditional Chinese Medicine, 2026 , 51 (1) : 173 -180 . DOI: 10.19540/j.cnki.cjcmm.20250930.701

基金

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国家自然科学基金青年科学基金项目(82204964)
中国博士后科学基金面上项目(2025M773957)
湖北省中医药管理局中医药科研面上项目(ZY2025M001)

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排序方式：

2026年第51卷第1期

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文章信息

doi: 10.19540/j.cnki.cjcmm.20250930.701

接收时间：2025-08-27
首发时间：2026-06-25
出版时间：2026-01-01

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出版历史

收稿日期：2025-08-27

基金

国家自然科学基金青年科学基金项目(82204964)

中国博士后科学基金面上项目(2025M773957)

湖北省中医药管理局中医药科研面上项目(ZY2025M001)

作者信息

^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

^3．云南中医药大学，云南昆明 650000

通讯作者:

龙清华，E-mail: 287201413@qq.com

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https://castjournals.cast.org.cn/joweb/zgzyzz/CN/10.19540/j.cnki.cjcmm.20250930.701

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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