Teng Yan, Zhang Meng-Qi, Wang Wen, Liu Li-Tao, Zhou Li-Ming, Miao Shi-Kun, Wan Li-Hong
Department of Pharmacology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, PR China.
BMC Complement Altern Med. 2014 Jan 14;14:23. doi: 10.1186/1472-6882-14-23.
Compound Danshen Tablet (CDT), a Traditional Chinese Medicine, has recently been reported to improve spatial cognition in a rat model of Alzheimer's disease. However, in vivo neuroprotective mechanism of the CDT in models of spatial memory impairment is not yet evaluated. The present study is aimed to elucidate the cellular mechanism of CDT on Aβ25-35-induced cognitive impairment in mice.
Mice were randomly divided into 5 groups: the control group (sham operated), the Aβ25-35 treated group, the positive drug group, and large and small dosage of the CDT groups, respectively. CDT was administered at a dose of 0.81 g/kg and 0.405 g/kg for 3 weeks. The mice in the positive drug group were treated with 0.4 mg/kg of Huperzine A, whereas the mice of the control and Aβ25-35 treated groups were administrated orally with equivalent saline. After 7 days of preventive treatment, mice were subjected to lateral ventricle injection of Aβ25-35 to establish the mice model of Alzheimer's disease. Spatial memory impairment was evaluated by Morris water maze test. Choline acetyltransferase (ChAT) contents in hippocampus and cortex were quantified by ELISA. The levels of cytokines, receptor of activated protein kinase C1 (RACK1) and brain-derived neurotrophic factor (BDNF) in hippocampus were measured by RT-PCR and ELISA.
The results showed that Aβ25-35 caused spatial memory impairment as demonstrated by performance in the Morris water maze test. CDT was able to confer a significant improvement in spatial memory, and protect mice from Aβ25-35-induced neurotoxicity. Additionally, CDT also inhibited the increase of TNF-α and IL-6 level, and increased the expression of choline acetyltransferase (ChAT), receptor of activated protein kinase C1 (RACK1) and brain-derived neurotrophic factor (BDNF) in brain as compared to model mice.
These findings strongly implicate that CDT may be a useful treatment against learning and memory deficits in mice by rescuing imbalance between cytokines and neurotrophins.
复方丹参片（CDT）作为一种中药，最近有报道称其可改善阿尔茨海默病大鼠模型的空间认知能力。然而，CDT在空间记忆损伤模型中的体内神经保护机制尚未得到评估。本研究旨在阐明CDT对Aβ25 - 35诱导的小鼠认知损伤的细胞机制。
将小鼠随机分为5组：对照组（假手术组）、Aβ25 - 35处理组、阳性药物组以及CDT大剂量组和小剂量组。CDT分别以0.81 g/kg和0.405 g/kg的剂量给药3周。阳性药物组小鼠用0.4 mg/kg石杉碱甲治疗，而对照组和Aβ25 - 35处理组小鼠口服等量生理盐水。预防性治疗7天后，小鼠侧脑室注射Aβ25 - 35以建立阿尔茨海默病小鼠模型。通过莫里斯水迷宫试验评估空间记忆损伤。用酶联免疫吸附测定法（ELISA）定量海马和皮质中胆碱乙酰转移酶（ChAT）的含量。用逆转录聚合酶链反应（RT-PCR）和ELISA检测海马中细胞因子、活化蛋白激酶C1受体（RACK1）和脑源性神经营养因子（BDNF）的水平。
结果表明，如莫里斯水迷宫试验所示，Aβ25 - 35导致空间记忆损伤。CDT能够显著改善空间记忆，并保护小鼠免受Aβ25 - 35诱导的神经毒性。此外，与模型小鼠相比，CDT还抑制了肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）水平的升高，并增加了脑中胆碱乙酰转移酶（ChAT）、活化蛋白激酶C1受体（RACK1）和脑源性神经营养因子（BDNF）的表达。
这些发现强烈表明，CDT可能通过挽救细胞因子和神经营养因子之间的失衡来有效治疗小鼠的学习和记忆缺陷。
