a Department of Pharmacy , Lanzhou University Second Hospital , Lanzhou , China.
b College of Pharmacy , Lanzhou University , Lanzhou , China.
Pharm Biol. 2019 Dec;57(1):22-28. doi: 10.1080/13880209.2018.1563619.
Epilepsy is a common life-threatening neurological disorder that is often drug-resistant and associated with cognitive impairment. The traditional Chinese patent medicine Songling Xuemaikang capsules (SXC) is clinically used for epilepsy therapy and alleviation of cognitive impairment.
This study investigates the neuronal protective effect of SXC combined with carbamazepine (CBZ) on epilepsy and cognitive impairment in kainic acid-kindled SD rats.
Kainic acid-kindled rats were established by injection of 0.45 μg kainic acid and randomly divided into 5 groups (n = 14): saline (sham-operated), control, CBZ, SXC and CBZ + SXC combined group. Rats in the treatment groups received CBZ (50 mg/kg/d), SXC (600 mg/kg/d) or combined CBZ (50 mg/kg/d) + SXC (600 mg/kg/d) via intragastric injection for 60 days. Epileptic behaviours, cognitive impairment, neuronal apoptosis and expression of p-Akt, Akt and caspase-9 were measured, and the alleviation of cognitive damage and neuronal apoptosis was analyzed.
The combined administration of SXC and CBZ significantly decreased the frequency of seizures (1.2 ± 0.3) and the number of episodes (1.3 ± 0.5) above stage III (p < 0.05). Neuronal apoptosis was improved (p < 0.01), and cognitive damage was ameliorated (p < 0.05).The level of p-Akt was enhanced (p < 0.01) whereas the expression of caspase-9 was evidently inhibited (p < 0.01) in the combined group.
The present findings confirm that the combined use of SXC with CBZ can effectively control epileptic seizures, alleviate damage to hippocampal neurons and protect against cognitive impairment. The mechanism of action might be related to the upregulation of p-Akt and inhibition of caspase-9 expression.
癫痫是一种常见的危及生命的神经系统疾病，通常对药物有抗药性，并伴有认知障碍。传统中药方剂松龄血脉康胶囊（SXC）临床上用于治疗癫痫和缓解认知障碍。
本研究旨在探讨 SXC 联合卡马西平（CBZ）对红藻氨酸致痫 SD 大鼠癫痫和认知障碍的神经保护作用。
采用 0.45μg 红藻氨酸注射建立红藻氨酸致痫大鼠模型，随机分为 5 组（n=14）：生理盐水（假手术）组、对照组、CBZ 组、SXC 组和 CBZ+SXC 联合组。治疗组大鼠分别给予 CBZ（50mg/kg/d）、SXC（600mg/kg/d）或联合 CBZ（50mg/kg/d）+SXC（600mg/kg/d）灌胃 60 天。测定癫痫发作行为、认知功能障碍、神经元凋亡及磷酸化 Akt（p-Akt）、Akt 和半胱氨酸天冬氨酸蛋白酶-9（caspase-9）的表达，分析认知损伤和神经元凋亡的缓解情况。
SXC 与 CBZ 联合给药可显著降低癫痫发作频率（1.2±0.3）和 III 级以上发作次数（1.3±0.5）（p<0.05）。神经元凋亡得到改善（p<0.01），认知损伤得到改善（p<0.05）。联合组 p-Akt 水平升高（p<0.01），caspase-9 表达明显抑制（p<0.01）。
本研究证实 SXC 与 CBZ 联合使用可有效控制癫痫发作，减轻海马神经元损伤，防止认知障碍。其作用机制可能与上调 p-Akt 和抑制 caspase-9 表达有关。
