[1]肖明月,白雅琪,王恒,等.白藜芦醇通过PI3K/Akt信号通路改善血管性痴呆大鼠认知功能作用机制[J].陕西中医,2026,(8):1039-1045,1051.[doi:DOI:10.3969/j.issn.1000-7369.2026.08.005]
　XIAO Mingyue,BAI Yaqi,WANG Heng,et al.Mechanism of resveratrol improving cognitive function in rats with vascular dementia via PI3K/Akt signaling pathway[J].,2026,(8):1039-1045,1051.[doi:DOI:10.3969/j.issn.1000-7369.2026.08.005]
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白藜芦醇通过PI3K/Akt信号通路改善血管性痴呆大鼠认知功能作用机制

《陕西中医》[ISSN:1000-7369/CN:61-1281/TN]

卷:
期数:
2026年8期
页码:
1039-1045,1051
栏目:
基础研究
出版日期:
2026-08-05

文章信息/Info

Title:
Mechanism of resveratrol improving cognitive function in rats with vascular dementia via PI3K/Akt signaling pathway
作者:
肖明月1; 白雅琪1; 王恒1; 翟一泽1; 杨建飞2
（1.黑龙江中医药大学研究生院，黑龙江 哈尔滨 150040；2.黑龙江中医药大学附属第一医院，黑龙江 哈尔滨 150040）
Author(s):
XIAO Mingyue1; BAI Yaqi1; WANG Heng1; ZHAI Yize1; YANG Jianfei2
（1.Graduate School of Heilongjiang University of Chinese Medicine,Harbin 150040,China；2.The First Affiliated Hospital of Heilongjiang University of Chinese Medicine,Harbin 150040,China）
关键词:
血管性痴呆; 白藜芦醇; PI3K/Akt信号通路; 海马神经元; 凋亡; 认知功能
Keywords:
Vascular dementia; Resveratrol; PI3K/Akt signaling pathway; Hippocampal neurons; Apoptosis; Cognitive function
分类号:
R 28
DOI:
DOI:10.3969/j.issn.1000-7369.2026.08.005
文献标志码:
A
摘要:
目的：探讨白藜芦醇对血管性痴呆（VD）模型大鼠认知功能及海马神经元凋亡的影响，探讨其是否通过磷脂酰肌醇3-激酶/蛋白激酶B（PI3K/Akt）信号通路发挥神经保护作用。方法：将68只雄性SD大鼠随机分为假手术组、模型组、白藜芦醇低、中、高剂量组、多奈哌齐组及联合用药组，每组8~10只。采用改良短暂性双侧颈总动脉闭塞法建立VD大鼠模型，各组连续干预4周。白藜芦醇低、中、高剂量组分别以12.5、25、50 mg/kg灌胃，多奈哌齐组以0.45 mg/kg多奈哌齐灌胃，联合用药组给予25 mg/kg白藜芦醇灌胃联合5 mg/kg LY294002腹腔注射。通过Y迷宫测试评估大鼠学习记忆能力；HE染色和尼氏染色观察海马CA1区神经元病理形态；TUNEL染色检测神经元凋亡；Western blot法检测海马组织B细胞淋巴瘤-2蛋白（Bcl-2）、半胱氨酸蛋白酶-3（Caspase-3）、半胱氨酸蛋白酶-9（Caspase-9）及PI3K/Akt通路相关蛋白表达情况。结果：与假手术组相比，模型组大鼠认知功能衰退（P＜0.05）。海马CA1区神经元形态损伤严重，凋亡指数升高（P＜0.05）。Caspase-9、Caspase-3表达升高，Bcl-2表达降低（P＜0.05）。PI3K、Akt磷酸化水平降低（P＜0.05）。与模型组相比，白藜芦醇各剂量组大鼠认知功能改善（P＜0.05）。神经元病理损伤得以修复，凋亡指数降低（P＜0.05），并下调Caspase-9、Caspase-3蛋白表达（P＜0.05），上调Bcl-2及PI3K、Akt磷酸化水平（P＜0.05）。联合用药后，白藜芦醇的神经保护及抗凋亡作用均逆转（P＜0.05）。结论：白藜芦醇可改善VD模型大鼠学习记忆能力，减轻海马神经元损伤，抑制神经元凋亡，其机制与激活PI3K/Akt信号通路密切相关。
Abstract:
Objective:To investigated effects of resveratrol on cognitive function and hippocampal neuronal apoptosis in a vascular dementia (VD) rat model,and explored whether it exerts neuroprotective effects through the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway.Methods:Sixty-eight male sprague-dawley rats were randomly divided into seven groups:sham group,model group,low-dose,medium-dose,and high-dose resveratrol groups,donepezil group,and combined treatment group,with 8-10 rats per group.Modified transient bilateral common carotid artery occlusion method was used to establish the VD rat model,followed by four weeks of continuous intervention.The low-dose,medium-dose,and high-dose resveratrol groups received oral gavage of 12.5,25,and 50 mg/kg,respectively.The donepezil group received 0.45 mg/kg donepezil via oral gavage,and the combined treatment group received 25 mg/kg resveratrol orally plus 5 mg/kg LY294002 intraperitoneally.Cognitive function was assessed using the Y-maze test.Neuronal morphology in the hippocampal CA1 region was examined by hematoxylin-eosin (HE) and Nissl staining.Neuronal apoptosis was detected by TUNEL staining.Aprotein expression levels of B-cell lymphoma-2 (Bcl-2),Caspase-3,Caspase-9,and PI3K/Akt pathway-related proteins were analyzed by Western blot.Results:Compared with the sham group,the model group exhibited impaired cognitive function (P＜0.05),severe neuronal morphological damage in the hippocampal CA1 region,and increased apoptosis index (P＜0.05).Expression of Caspase-9 and Caspase-3 was elevated,while Bcl-2 expression was reduced (P＜0.05).Phosphorylation levels of PI3K and Akt were decreased (P＜0.05).Compared with the model group,all resveratrol-treated groups showed improved cognitive function (P＜0.05),repaired neuronal pathological damage,reduced apoptosis index (P＜0.05),downregulated expression of Caspase-9 and Caspase-3 (P＜0.05),and upregulated expression of Bcl-2 as well as phosphorylated PI3K and Akt (P＜0.05).However,after combined treatment with LY294002,the neuroprotective and anti-apoptotic effects of resveratrol were reversed (P＜0.05).Conclusion:Resveratrol improves learning and memory ability in VD rat models,reduces hippocampal neuronal injury,and inhibits neuronal apoptosis,mechanisms closely associated with activation of the PI3K/Akt signaling pathway.

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备注/Memo

备注/Memo:
黑龙江省“双一流”学科协同创新项目（LJGXCG2024-P40）；世界中医药学会联合会科技专项课题（WFCMS2024006）；全国名老中医药专家传承工作室建设项目（国中医药人教函〔2022〕75号）；黑龙江中医药大学校基金-博士创新基金资助项目(2018bs09)
更新日期/Last Update: 2026-08-13