To explore the molecular mechanism ofWendan Decoction(温胆汤)improving cognitive impairment in schizophrenia from the perspective of neuronal synaptic plasticity by using glutamate-induced HT22 cells as a cellularmodel of schizophrenia and detecting synaptic plasticity related proteins,postsynaptic density protein-95(PSD-95),growth associated protein-43(GAP-43),c-Jun NH2-terminal kinase-interacting protein-3(JIP-3)and connexin-43(Cx-43).
The SD ratswere randomly divided into four groups:Wendan Decoction 40 g/kg,30 g/kg and 20 g/kg groups and clozapine 0.02 g/kg group. Each drug group was given the corresponding dose of drug by gavage,once a day. After seven days,the ratswere be killed to collect blood and prepare the drug-containing serum. CCK8 assay was used to determine the concentration and time point of glutamate action on astrocytes. HT22 cells at 10 mmol/L glutamate for 24 h were used as a cellmodel to detect the effect of Wendan Decoction-containing serum on the apoptosis rate of HT22 cells by flow cytometry. RT-qPCR was used to detect the expressions of Psd95,Gap43,Jip3 and Cx43 mRNA in HT22 cells. The expressions of PSD-95,GAP-43,JIP-3 and Cx-43 proteins in HT22 cellswere detected by Western blot.
According to the results of the effectof different concentrations of glutamate on the proliferation rate of HT22 cells,10 mmol/L glutamate HT22 cells for 24 h were determined as the cell experimental conditions. Compared with thatof the normal control group,the apoptosis rate of HT22 cells in the glutamate model group increased significantly. The mRNA and protein expressions of PSD-95,GAP-43,JIP-3 and Cx-43 were also significantly down-regulated(P<0.01). Compared with that of the glutamate model group,the apoptosis rate of HT22 cells in Wendan Decoction-containing serum groups were significantly decreased and the expressions of PSD-95,GAP-43,JIP-3,Cx-43 mRNA and protein significantly up-regulated(P<0.05 or P<0.01).
Wendan Decoction may be to reduce apoptosis in neurons and up-regulate the expressions of PSD-95,GAP-43,JIP-3 and Cx-43,and then regulate synaptic plasticity,in order to effectively improve cognitive deficits in schizophrenia.
| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |