科研之友
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摘要
Objective: To study the ameliorating effect of retigabine (RTG) on chronic stress-induced depression-like symptoms in rats, and to explore the possible molecular mechanism. Methods: 32 SD rats were randomly divided into control group, model group, RTG high dose (4 mg?kg-1) and RTG low dose (2 mg?kg-1) groups. Long-term repeated low-temperature water immersion restraint method was used to establish the rat chronic stress model. Open field test, forced swimming test and sucrose preference test were conducted to evaluate the degree of depression-like symptoms of rats. The histopathological changes in hippocampus of rats were detected by HE staining and Nissl staining. The levels of brain derived neurotrophic factor (BDNF), synaptophysin (SYP), glucose regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax) and Caspase-3 protein in hippocampus were determined by using Western Blot analysis. Results: In the chronic stress rat model, RTG markedly increased the total distance of movement, average movement speed, and stationary time in the central area in the open field experiment. RTG significantly increased the sucrose consumption ratio of rats and shortened the immobility time of forced swimming. In addition, RTG effectively improved the tissue lesion of hippocampus, markedly increased the protein expression of BDNF, SYP, GRP78 and Bcl-2 and decreased that of CHOP, Bax and Caspase-3. Conclusion: RTG has protective effect on depression-like symptoms and hippocampal structural pathological damage in rats induced by long-term repeated low-temperature water immersion. Its mechanism may be attributed to alleviating the endoplasmic reticulum stress of hippocampal nerve cells, reducing cell apoptosis, and improving neuroplasticity.
