Objective To investigate the effect of carbamazepine (CBZ) on Kv7.4 channels of dopaminergic (DA) neurons in the ventral tegmental area (VTA) of the midbrain of epileptic rats. Methods 50 male Wistar rats were randomly divided into 5 groups: control group, epilepsy group, and low, medium, high concentration CBZ group, 10 in each group. Except control group, rats in other groups were induced epilepsy with lithium chloride and pilocarpine to establish epilepsy rat model. After the model was successfully constructed, the rats in low, medium, and high concentration CBZ groups were given CBZ (10, 30, and 50 mg/kg) by gavage respectively, while rats in control group and epilepsy group were given the same amount of normal saline by gavage once a day for 7 days. The behavior changes of rats were observed. The malondialdehyde (MDA), glutathione (GSH) content and superoxide dismutase (SOD) activity in VTA were determinate by spectrophotometric. The protein expression of tyrosine hydroxylase (TH) and kv7.4 in VTA were detected by immunofluorescence and laser confocal microscopy. Western blotting was used to detecte the TH and Kv7.4 expression. Results No abnormal behavior showed with rats in control group. After pilocarpine injection, rats in epilepsy group experienced symptoms such as convulsions, chewing, and salivation, and the symptoms in low, medium, and high concentration CBZ group were alleviated. Compared with rats in control group, the MDA content of the rats in epilepsy group was significantly increased (P<0.05), the GSH content, SOD activity, number of DA neurons in the VTA region, and the expression of TH and Kv7.4 protein were significantly reduced (P<0.05). Compared with rats in epilepsy group, the seizure latency, GSH content, SOD activity, number of DA neurons in VTA area, and TH and Kv7.4 protein expression levels significantly increased in the low, medium and high concentration CBZ group (P<0.05); seizure rate and MDA content significantly decreased in the medium and high concentration CBZ group (P<0.05). Conclusions CBZ could alleviate oxidative stress response in brain of epileptic rats, promote DA neuron activity at VTA, activate Kv7.4 channels, and relieve epileptic seizures.
| 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 |