Weixiang Wu*, Wanli Dong*#, Zhengxiang Ji*, Jingye Lu**
*Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China - **Department of Neurology, Taixing People’s Hospital, Taixing, 225400, China
Objective: To investigate the expression of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in hippocampal tissues of rats with vascular dementia, and the monoamine transmitters 5-HT (5-HT), dopamine (DA) and norepinephrine (NE) in cerebral cortex.
Methods: 120 clean healthy male SD rats were selected for adaptive culture for 2 weeks. Rats were randomly divided into model group, sham operation group, low-dose butylphthalide group and high-dose butylphthalide group, with 30 rats in each group. Sham operation group, only bilateral common carotid arteries were isolated without ligation. Model group: bilateral common carotid arteries were separated. Low-dose butylphthalide group: ligated bilateral common carotid artery and intraperitoneally injected 3 mg/kg butylphthalide sodium chloride injection; High-dose butylphthalide group: ligated bilateral common carotid artery and intraperitoneally injected 7 mg/kg butylphthalide sodium chloride injection. The model group and the sham operation group were given equal doses of saline intraperitoneally. Morris water maze experiment was used to detect the changes in the time of escape latency, the exploration time of the platform area, the time of effective zone residence and the number of errors. The expression levels of TNF- a and IL-1β in hippocampal tissues of rats were detected by elisa. The changes of 5-HT, DA and NE in cerebral cortex of rats were determined by immunofluorescence. The changes of hippocampal tissues in each group were observed by HE staining.
Results: Compared with the model group, the escape latency time and the number of errors in the high-dose and low-dose butylphthalide groups were significantly reduced, and the exploration time in the plateau area and the stay time in the effective area were significantly increased (P<0.05). Compared with the model group, the levels of TNF-α and IL-1β in the high-dose, low-dose and sham operation groups were significantly increased, and the levels of TNF-α and IL-1β in the model group were significantly higher than those at 1 and 6 weeks after the operation (P<0.05). Compared with the model group, the levels of 5-HT, DA and NE in the high-dose, low-dose and sham operation groups were significantly increased (P<0.05). The hippocampal nerve cells in the sham operation group were arranged normally, with dense and large round neurons, obvious nucleoli and distinct cell stratification. The shapes of hippocampal neurons in the high-dose and low-dose butylphthalide groups were regular, with obvious stratification, and there was no significant difference between the two groups. In the model group, the pyramidal cells in the hippocampal of rats were arranged in disorder, and the shape of the cells were irregular, connective tissue such as glial cells proliferate, nodular formation, and the level disappeared.
Conclusion: Butylphthalide can inhibit the expression of TNF-α and IL-1β in hippocampus of rats with vascular dementia, reduce its damage to the nervous system, and increase the levels of 5-HT, DA and NE in vascular dementia rats, and improve the learning and memory ability of rats.
butyl phenyl peptide, vascular dementia, hippocampus, TNF-α, IL-1β, 5-HT, DA, NE.