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