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复方丹参滴丸单独及联合卡马西平对红藻氨酸诱导的颞叶癫痫及认知障碍大鼠的保护作用。

Protective effect of compound Danshen (Salvia miltiorrhiza) dripping pills alone and in combination with carbamazepine on kainic acid-induced temporal lobe epilepsy and cognitive impairment in rats.

机构信息

a Department of Pharmacy , Lanzhou University Second Hospital , Lanzhou , China.

b Department of Pharmacy , Huaihe Hospital of Henan University , Kaifeng , China.

出版信息

Pharm Biol. 2018 Dec;56(1):217-224. doi: 10.1080/13880209.2018.1432665.

Abstract

CONTEXT

Temporal lobe epilepsy (TLE) is resistant to antiepileptic drugs (AEDs) and is associated with cognitive impairment. The modern Chinese medicine, compound Danshen dripping pills (CDDP), is clinically effective in treating epilepsy and improving cognitive impairment.

OBJECTIVE

This study evaluated the protective effects of CDDP alone and in combination with carbamazepine (CBZ) on kainic acid-induced TLE and cognitive impairment in rats.

MATERIALS AND METHODS

Sprague-Dawley rats were randomly divided into five groups: control (sham operated), model, CDDP, CBZ and combined. A TLE model was then created via bilateral intrahippocampal injection of 0.35 μg kainic acid (KA). Rats received CDDP (85 mg/kg), CBZ (100 mg/kg) or combined (85 mg/kg CDDP +100 mg/kg CBZ) via intragastric administration for 90 d, respectively. Seizure intensity, apoptosis and glial cell line-derived neurotrophic factor (GDNF) were measured. Furthermore, the improvement in cognitive impairment and hippocampal neuronal damage was evaluated.

RESULTS

CDDP combined with CBZ significantly decreased seizure severity and frequency (p < 0.05) and ameliorated cognitive impairment (p < 0.05). The model group showed a significant reduction of neurons and Bcl-2/Bax expression in the hippocampus CA3 area (p < 0.01), the combined groups significantly reversed these change (p < 0.01). GDNF expression in the combined groups showed a clear increase over the model group (p < 0.05).

CONCLUSION

These findings support the use of CDDP as an adjuvant drug for the treatment of TLE and cognitive deficit. Its mechanism might be related to an anti-apoptosis effect and up-regulation of GDNF.

摘要

背景

颞叶癫痫(TLE)对抗癫痫药物(AEDs)有抗性,并与认知障碍有关。中药复方丹参滴丸(CDDP)在临床上对治疗癫痫和改善认知障碍有效。

目的

本研究评估 CDDP 单独使用和与卡马西平(CBZ)联合使用对红藻氨酸诱导的 TLE 和大鼠认知障碍的保护作用。

材料和方法

Sprague-Dawley 大鼠随机分为五组:对照组(假手术)、模型组、CDDP 组、CBZ 组和联合组。通过双侧海马内注射 0.35μg 红藻氨酸(KA)建立 TLE 模型。大鼠分别经灌胃给予 CDDP(85mg/kg)、CBZ(100mg/kg)或联合(85mg/kg CDDP+100mg/kg CBZ)90d。测量癫痫发作强度、凋亡和胶质细胞源性神经营养因子(GDNF)。此外,评估认知障碍和海马神经元损伤的改善情况。

结果

CDDP 联合 CBZ 可显著降低癫痫发作严重程度和频率(p<0.05),并改善认知障碍(p<0.05)。模型组海马 CA3 区神经元和 Bcl-2/Bax 表达减少(p<0.01),联合组明显逆转了这些变化(p<0.01)。联合组 GDNF 表达明显高于模型组(p<0.05)。

结论

这些发现支持将 CDDP 作为治疗 TLE 和认知缺陷的辅助药物。其机制可能与抗凋亡作用和 GDNF 上调有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75b2/6130614/58c0ea8e5751/IPHB_A_1432665_F0001_C.jpg

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