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通腑疗法增强补肾中药对Aβ1-42诱导的阿尔茨海默病模型大鼠海马胆碱能系统的神经保护作用。

Therapy of Dredging the Bowels Enhanced the Neuroprotective Effect of Nourishing Kidney Herbs on Hippocampal Cholinergic System in Alzheimer's Disease Model Rat Induced by A 1-42.

作者信息

Feng Lu-Da, Tian Yang, Wang Xin, Dai Run, Cai Song, Cao Yu-Jia, Si Yin-Chu

机构信息

Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China.

Dongfang Hospital, Beijing University of Chinese Medicine, Beijing 100078, China.

出版信息

Evid Based Complement Alternat Med. 2018 Sep 12;2018:3282385. doi: 10.1155/2018/3282385. eCollection 2018.

Abstract

BACKGROUND

Therapy of nourishing kidney has been used for treating memory deficits of Alzheimer's disease (AD) for thousands of years based on traditional Chinese medicine. However, we found the therapy of dredging the bowels could alleviate both memory deficits and mental symptoms of AD in clinic.

OBJECTIVE

To determine whether the therapy of dredging the bowels could enhance the neuroprotective effect of nourishing kidney herbs for treating AD rats, and to explore the underlying mechanism of the combination of nourishing kidney and dredging the bowels (NKDB) herbs.

METHODS

60 rats were randomly divided into sham-operated group (SOG), model group (MG), nourishing kidney group (NKG), dredging the bowels group (DBG), nourishing kidney and dredging the bowels group (NKDBG), and donepezil hydrochloride group (DHG). The model establishment was performed by injecting A 1-42 into the hippocampal CA1 region. Animals received aqueous solution of Chinese herbal medicine or western medicine while SOG received only distilled water. Ability of learning and memory were assessed by Morris water maze. Acetylcholinesterase(AChE) and choline acetyltransferase (ChAT) activity and positive cells in the hippocampus were detected by the biochemical and immunofluorescent assay.

RESULTS

All rats were in the same baseline. While after model establishment, ability of learning and memory of MG, NKG, DBG, NKDBG, and DHG were significantly impaired compared with SOG. Whereas after treatment, ability of learning and memory of NKG, DBG, NKDBG, and DHG were significantly improved compared with MG. Additionally, AChE activity of NKG, DBG, and NKDBG was significantly decreased, meanwhile ChAT activity showed an increased tendency. The number of AChE-positive cells and ChAT-positive cells of both NKDBG and DHG were significantly decreased and increased respectively, superior to those when compared with NKG and DBG. What's more, there was no significant difference between NKDBG and DHG.

CONCLUSION

Therapy of dredging the bowels could enhance the neuroprotective effect of nourishing kidney herbs by reversing morphological damage of hippocampal cholinergic system. Furthermore, treatment with NKDB herbs could be effectively against AD, providing a practical therapeutic strategy in clinic.

摘要

背景

基于传统中医理论,补肾疗法用于治疗阿尔茨海默病(AD)的记忆缺陷已有数千年历史。然而,我们在临床中发现通腑疗法可缓解AD的记忆缺陷和精神症状。

目的

确定通腑疗法是否能增强补肾中药对AD大鼠的神经保护作用,并探讨补肾与通腑(NKDB)中药联合应用的潜在机制。

方法

将60只大鼠随机分为假手术组(SOG)、模型组(MG)、补肾组(NKG)、通腑组(DBG)、补肾通腑组(NKDBG)和盐酸多奈哌齐组(DHG)。通过向海马CA1区注射Aβ1-42建立模型。动物接受中药水溶液或西药治疗,而SOG仅接受蒸馏水。通过Morris水迷宫评估学习和记忆能力。采用生化和免疫荧光分析法检测海马中乙酰胆碱酯酶(AChE)和胆碱乙酰转移酶(ChAT)活性及阳性细胞。

结果

所有大鼠基线相同。造模后,MG、NKG、DBG、NKDBG和DHG的学习和记忆能力与SOG相比均显著受损。而治疗后,NKG、DBG、NKDBG和DHG的学习和记忆能力与MG相比均显著改善。此外,NKG、DBG和NKDBG的AChE活性显著降低,同时ChAT活性呈上升趋势。NKDBG和DHG的AChE阳性细胞数和ChAT阳性细胞数分别显著减少和增加,优于NKG和DBG。此外,NKDBG和DHG之间无显著差异。

结论

通腑疗法可通过逆转海马胆碱能系统的形态学损伤增强补肾中药的神经保护作用。此外,NKDB中药治疗可有效对抗AD,为临床提供了一种切实可行的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/abe6/6157172/7055f1c7599f/ECAM2018-3282385.001.jpg

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