白藜芦醇对血管性痴呆大鼠学习记忆能力及海马CA1区SIRT1、STAT3及IL-17表达的影响

doi:10.12092/j.issn.1009-2501.2026.06.013

摘要/Abstract

摘要：

目的: 研究白藜芦醇（resveratrol，Rsv）对血管性痴呆（vascular dementia，VD）大鼠学习记忆能力及海马CA1区沉默信息调节因子1（SIRT1）、信号转导与转录激活因子3（STAT3）及白细胞介素-17（IL-17）表达的影响，探讨白藜芦醇的可能治疗机制。方法: 成年健康雄性SD大鼠，随机分为假手术组（Sham组），假手术+白藜芦醇组（Sham+Rsv组），手术组。手术组采用双侧颈总动脉永久结扎法建立VD模型，从中筛选出建模成功的大鼠，随机分为VD组和VD+白藜芦醇组（VD+Rsv组），每组8只。VD+Rsv组以及Sham+Rsv组均给予白藜芦醇（20 mg/kg）灌胃30 d。分别采用Morris水迷宫测试大鼠的学习记忆能力，免疫组织化学法和Western blot检测海马CA1区SIRT1、STAT3和IL-17A的蛋白表达。采用酶联免疫吸附试验检测炎症因子IL-17的分泌。结果: 与Sham组相比，Sham+Rsv组各项测定结果差异无统计学意义。与Sham组相比，VD组大鼠逃避潜伏期显著增加，首次穿越平台区域潜伏期显著延长，目标象限停留时间显著缩短，穿越平台次数显著减少（P<0.001）；海马CA1区SIRT1阳性神经元数量显著减少，平均灰度值显著增高（P<0.001），蛋白表达量显著减少（P<0.01）；STAT3和IL-17A阳性神经元数量显著增加，平均灰度值显著降低（P<0.001），蛋白表达量显著增加（P<0.01）；炎症因子IL-17的分泌量显著增加（P<0.001）。VD大鼠经白藜芦醇治疗4周后，与VD组比较，VD+Rsv组逃避潜伏期显著缩短（P<0.001），首次穿越平台区域潜伏期显著缩短（P<0.001），目标象限停留时间显著延长（P<0.05），穿越平台次数显著增多（P<0.01）；海马CA1区SIRT1阳性神经元数量显著增加（P<0.01），平均灰度值显著减少（P<0.001），蛋白表达量显著增加（P<0.05）；STAT3和IL-17A阳性神经元数量显著减少（P<0.05，P<0.001），平均灰度值显著增加（P<0.001），蛋白表达量显著减少（P<0.05），炎症因子IL-17分泌显著减少（P<0.05）。结论: 白藜芦醇能够缓解VD诱导的学习记忆能力降低和神经炎症，其作用机制可能与调控SIRT1、STAT3及IL-17表达有关。

关键词: 血管性痴呆, 白藜芦醇, SIRT1, STAT3, 炎症, 学习记忆

Abstract:

AIM: To investigate the effects of resveratrol (Rsv) on learning and memory abilities, as well as the expressions of silent information regulator 1 (SIRT1), signal transducer and activator of transcription 3 (STAT3), and interleukin-17 (IL-17) in the hippocampal CA1 region of rats with vascular dementia (VD), and to explore the potential therapeutic mechanism of resveratrol. METHODS: Adult healthy male Sprague-Dawley (SD) rats were randomly divided into the sham operation group (Sham group), sham operation + resveratrol group (Sham+Rsv group), and the operation group. The vascular dementia (VD) model was established in the operation group by permanent ligation of bilateral common carotid arteries. Rats with successful model establishment were screened out and randomly assigned to the VD group and VD + resveratrol group (VD+Rsv group), with 8 rats in each group. Both the VD+Rsv group and Sham+Rsv group were given Rsv (20 mg/kg) by gavage for 30 consecutive days. The learning and memory abilities of rats were evaluated using the Morris water maze test. The protein expressions of SIRT1, STAT3, and IL-17A in the hippocampal CA1 region were detected by immunohistochemistry and Western blotting. Additionally, the secretion of the inflammatory factor IL-17 was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: No statistically significant differences were observed in all measured outcomes between the Sham+Rsv group and the Sham group. Compared with the Sham group, the VD group exhibited a significant increase in escape latency, a prolonged latency to first cross the platform area, a shortened residence time in the target quadrant, and a reduced number of platform crossings (all P<0.001). In the hippocampal CA1 region of the VD group, the number of SIRT1-positive neurons was significantly decreased, with a marked increase in the average gray value (P<0.001) and a reduction in protein expression (P<0.01). Conversely, the numbers of STAT3-positive and IL-17A-positive neurons were significantly increased, accompanied by a significant decrease in the average gray value (P<0.001) and an elevation in their protein expressions (P<0.01). Additionally, the secretion of the inflammatory factor IL-17 was significantly increased in the VD group (P<0.001). After 4 weeks of resveratrol treatment in VD rats, compared with the VD group, the VD+Rsv group showed a significant reduction in escape latency (P<0.001), a shortened latency to first cross the platform area (P<0.001), an extended residence time in the target quadrant (P<0.05), and an increased number of platform crossings (P<0.01). In the hippocampal CA1 region of the VD+Rsv group, the number of SIRT1-positive neurons was increased (P<0.01), with a significant decrease in the average gray value (P<0.001) and an increase in protein expression (P<0.05). For STAT3 and IL-17A, the numbers of positive neurons were reduced (P<0.05 for STAT3, P<0.001 for IL-17A), with a significant increase in the average gray value (P<0.001) and a decrease in their protein expressions (P<0.05 for both). Moreover, the secretion of the inflammatory factor IL-17 was decreased in the VD+Rsv group (P<0.05). CONCLUSION: Rsv can alleviate VD-induced impairments in learning and memory abilities as well as neuroinflammation, and its mechanism of action may be related to the regulation of the expressions of SIRT1, STAT3, and IL-17.

Key words: vascular dementia, resveratrol, SIRT1, STAT3, inflammation, learning and memory

中图分类号:

R965.2

王薇, 熊钱颖, 丁见, 吴锋, 马同军. 白藜芦醇对血管性痴呆大鼠学习记忆能力及海马CA1区SIRT1、STAT3及IL-17表达的影响[J]. 中国临床药理学与治疗学, 2026, 31(6): 836-843.

Wei WANG, Qianying XIONG, Jian DING, Feng WU, Tongjun MA. Effects of resveratrol on learning and memory abilities and the expression of SIRT1, STAT3, and IL-17 in the hippocampal CA1 region in VD rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2026, 31(6): 836-843.

图/表 4

图 1

Fig.1 Comparison of Morris water maze test results of rats in each group ($\bar x $±s, n=8) A: escape latency for finding the platform during the training period; B: average swimming speed of rats in each group during the probe test; C: representative swimming trajectories of rats in each group during the probe test; D: latency to first cross the platform area in rats of each group during the probe test; E: quantitative analysis of the time spent in the target quadrant by rats of each group during the probe test on day 6; F: average number of crossings in the target quadrant by rats of each group. *P<0.05, **P<0.01, ***P<0.001.

图 2

Fig.2 Comparison of the positive expression levels of SIRT1, STAT3, and IL-17A proteins in the hippocampal CA1 region of rats in each group ($\bar x $±s, n=8) A: representative images of the positive expression of the three proteins in the hippocampal CA1 region of rats in each group; B: average gray values of the positive expression of the three proteins in the hippocampal CA1 region of rats in each group; C: quantitative analysis of the three types of positive neurons in the hippocampal CA1 region of rats in each group. Scale bars: 50 µm; *P<0.05, **P<0.01, ***P<0.001.

图 3

Fig.3 Comparison of the expression levels of SIRT1, STAT3, and IL-17A proteins in the hippocampal CA1 region of rats in each group ($\bar x $±s, n=8) A: representative Western blot bands of SIRT1, STAT3, IL-17A, and β-actin in rats of each group; B-D: quantitative analysis of the relative expression levels of SIRT1, STAT3, and IL-17A proteins. *P<0.05, **P<0.01.

图 4 *P<0.05, ***P<0.001.

Fig.4 Comparison of IL-17A concentrations in the hippocampal CA1 region of rats in each group ($\bar x $±s, n=8) *P<0.05, ***P<0.001.

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