党参-茯苓-甘草水提物通过激活胆碱能信号通路改善痴呆小鼠的学习记忆功能

Aqueous Extract of Radix Codonopsis-Poria cocos-Glycyrrhizae Radix Improves the Learning and Memory Functions in Mice through Activating the Cholinergic Signaling Pathway

该研究深入探讨“药食两用”中药党参、茯苓、甘草水提物改善学习记忆障碍小鼠的作用机制。小鼠随机分为正常组、模型组、党参-茯苓-甘草组(10、20、40 g/kg)和阳性药组(盐酸多奈哌齐,1.5 mg/kg),每组10只,不间断给药30 d(10 mL/(kg·d))。腹腔注射氢溴酸东莨菪碱建立学习记忆障碍模型(2 mg/kg,5 d),Morris水迷宫实验考察小鼠行为变化;ELISA检测小鼠海马组织中乙酰胆碱(acetylcholine,Ach)和乙酰胆碱脂酶(acetylcholinesterase,AchE)水平;Western blot测定胆碱能信号通路相关蛋白及磷酸化表达量。结果发现,与模型组比较,高剂量组(40 g/kg)小鼠在Morris水迷宫实验中穿过平台次数增加了5.48次,在第Ⅲ象限时间、路程分别增加了17.41%、14.39%;小鼠海马中ACh水平升高了26%,AChE水平降低了11.9%;中、高剂量组小鼠海马α7-nAChR、CaMKⅡ、p-ERK1/2、p-CREB蛋白表达明显增强。这表明党参-茯苓-甘草水提物能够对学习记忆障碍小鼠起到改善作用,其机制可能与激活海马组织胆碱能突触通路并上调相关蛋白的表达有关。该研究为潞党参、茯苓、甘草这三味“药食两用”中药资源改善学习记忆障碍功效提供研究基础,为开发山西省道地药材潞党参提供研究方向。

This research thoroughly investigated the mechanism of action for the aqueous extract of Chinese medicine Radix Codonopsis-Poria cocos-Glycyrrhizae Radix to ameliorate the learning and memory impairment in mice.The mice were randomly divided into a normal group,a model group,and Radix Codonopsis-Poria cocos-Glycyrrhizae Radix treatment groups(10,20,40 g/kg)and a positive drug group(donepezil,1.5 mg/kg),with 10 mice for each group and 30 days of administration without interruption(10 mL/(kg·d)).The learning and memory impairment model was established by the intraperitoneal injection of scopolamine hydrobromide(2 mg/kg for 5 days).The behavioral changes of the mice were examined by the Morris water maze test,and the ACh and AChE levels in the hippocampal tissues of mice were evaluated by ELISA.The protein expression or phosphorylation related to the cholinergic signaling pathway were determined by Western blotting.The results showed that compared with the model group,the high-dose(40 g/kg)mice crossed the platform 5.48 times more,with their time in the third quadrant increased by 17.41%and the distance in the third quadrant increased by 14.39%in the Morris water maze test.The levels of ACh and AChE in the mouse hippocampal tissues of the middle dose group increased by 29%and decreased by 13.7%,respectively.The levels of Ach and AchE in the hippocampus of high-dose mice increased by 26%and decreased by 11.9%(p<0.05),respectively;The expression ofα7-nAChR,CaMKⅡ,p-ERK1/2,p-CREB proteins in the hippocampus of medium-and high-dose mice increased significantly.These results suggest that the aqueous extract of Radix Codonopsis-Poria cocos-Glycyrrhizae Radix can ameliorate learning and memory impairments in mice,and its mechanism of action may be related to the activation of the cholinergic synaptic signaling pathway in the hippocampus and up-regulating the expression of related proteins.This research provides a research foundation for ameliorating learning and memory impairments using traditional Chinese medicine resources such as Radix Codonopsis,Poria cocos and Glycyrrhizae Radix,and a research direction for the development of the authentic medicinal material,Lu Codonopsis,in Shanxi province.