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[汤剂通过调节海马NMDAR亚基上调ASIC1改善大鼠癫痫后的认知障碍]

[ Decoction improves cognitive impairment after epilepsy in rats by regulating hippocampal NMDAR subunits upregulating ASIC1].

作者信息

Yu Yunhong, Xie Wei, Li Hui

机构信息

Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Institute of Guangdong Geriatric, Southern Medical University, Guangzhou 510080, China.

School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China.

出版信息

Nan Fang Yi Ke Da Xue Xue Bao. 2025 Jul 20;45(7):1506-1512. doi: 10.12122/j.issn.1673-4254.2025.07.17.

Abstract

OBJECTIVES

To explore the therapeutic mechanism of (CHSG) Decoction for improving cognitive impairment in rats with epilepsy induced by lithium chloride and pilocarpine.

METHODS

Male SD rat models of cognitive impairment model after epilepsy induced by intraperitoneal injection with lithium chloride and pilocarpine were randomly divided into 5 groups (=12) for treatment with daily gavage of saline, donepezil (90 mg/kg), or CHSG Decoction at 2.5, 5.0, 10, 20 and 40 g/kg for 4 consecutive weeks, with 10 rats with intraperitoneal injection with saline as the blank control group. Morris water maze test was used to evaluate cognitive and behavioral changes of the rats after treatment. The mRNA and protein expressions of ASIC1, NR1, NR2A and NR2B in the hippocampus of rats were detected using RT-qPCR and Western blotting.

RESULTS

Compared with those with saline treatment, the rat models treated with CHSG Decoction at 5 and 10 g/kg showed significantly shortened escape latency and prolonged stay in the target quadrant with increased number of platform crossings in Morris water maze test. CHSG Decoction treatment at the two doses significantly increased ASIC1, NR1, NR2A and NR2B protein expressions in the hippocampus of the rat models, and their mRNA expression levels were all increased significantly after the treatment at the doses above 2.5 g/kg.

CONCLUSIONS

CHSG Decoction can improve cognitive impairment in rats after epilepsy possibly by regulating the expression and channel activity of NMDAR protein and its subunit protein via upregulating ASIC1 to modulate neuronal excitability and synaptic plasticity in the hippocampus.

摘要

目的

探讨柴芍桂枝汤改善氯化锂-匹罗卡品诱导癫痫大鼠认知障碍的治疗机制。

方法

将腹腔注射氯化锂和匹罗卡品诱导癫痫后认知障碍的雄性SD大鼠模型随机分为5组(每组n = 12),分别每日灌胃给予生理盐水、多奈哌齐(90 mg/kg)或2.5、5.0、10、20和40 g/kg柴芍桂枝汤,连续给药4周,另10只腹腔注射生理盐水的大鼠作为空白对照组。采用Morris水迷宫试验评估大鼠治疗后的认知和行为变化。采用RT-qPCR和蛋白质免疫印迹法检测大鼠海马中ASIC1、NR1、NR2A和NR2B的mRNA和蛋白表达。

结果

与生理盐水治疗组相比,5和10 g/kg柴芍桂枝汤治疗的大鼠模型在Morris水迷宫试验中逃避潜伏期显著缩短,在目标象限停留时间延长,穿越平台次数增加。两剂量柴芍桂枝汤治疗均显著增加大鼠模型海马中ASIC1、NR1、NR2A和NR2B蛋白表达,2.5 g/kg以上剂量治疗后其mRNA表达水平均显著升高。

结论

柴芍桂枝汤可能通过上调ASIC1调节神经元兴奋性和海马突触可塑性,从而调控NMDAR蛋白及其亚基蛋白的表达和通道活性,改善癫痫后大鼠的认知障碍。

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本文引用的文献

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The Role of ASIC1a in Epilepsy: A Potential Therapeutic Target.ASIC1a 在癫痫中的作用:一个潜在的治疗靶点。
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