摘要
目的探讨红豆杉多糖通过PI3K/Akt信号通路调节神经元自噬缓解阿尔茨海默病(AD)大鼠神经损伤的作用机制。方法取SD大鼠30只,随机取10只设为空白对照组,剩余20只大鼠采用侧脑室微量注射Aβ25-35建立AD大鼠动物模型。建模完毕后随机分为模型对照组与红豆杉多糖组,每组10只大鼠。模型对照组与空白对照组注射等量生理盐水,红豆杉多糖组采用红豆杉多糖溶液灌胃。对3组大鼠脑部组织行HE染色,观察神经损伤情况;采用Western Blot法测定3组大鼠PI3K、p-Akt/Akt、p-mTOR/mTOR及Beclin1蛋白量;采用Morris水迷宫测定3组大鼠记忆能力和空间探索能力。结果与空白对照组比较,模型对照组PI3K、p-mTOR/mTOR、p-Akt/Akt蛋白表达量上调,Beclin1蛋白表达量下调(P<0.05)。与模型对照组比较,红豆杉多糖组p-mTOR/mTOR、p-Akt/Akt下调,差异有统计学意义(P<0.05),PI3K和Beclin1表达变化不大(P>0.05)。与空白对照组比较,模型对照组逃避潜伏期延长,穿越平台次数减少;与模型对照组相比,红豆杉多糖组干预后潜伏期、平台滞留时间缩短,穿越平台次数增多,差异有统计学意义(P<0.05)。结论红豆杉多糖用于AD大鼠中能减轻神经损伤,有助于改善大鼠记忆和空间探索能力,其机制可能与PI3K/Akt信号通路调节神经元自噬有关。
AIM To investigate the mechanism of Taxus polysaccharide to alleviate the neural damage through regulating autophagy mediated by PI3 K/Akt signal pathway in Alzheimer’s disease(AD)rats.METHODS Thirty SD rats were involved in this study,and 10 were randomly selected as the blank control group.The remaining 20 rats were prepared for AD rat models by Aβ25-35 injection in the lateral ventricles.After modeling,they were randomly divided into model control group and Taxus polysaccharide group,with 10 in each group.The rats in the Taxus polysaccharide group were given Taxus polysaccharide solution by intragastric administration,while those in the model control and blank control group were given the same volume of normal saline.The brain tissues of the 3 groups were stained with HE staining fluid to observe the nerve injury degree;the protein expression levels of PI3 K,p-Akt/Akt,p-mTOR/mTOR and Beclin 1 were measured by Western blot;the memory ability and space exploration ability were measured by Morris water maze.RESULTS Compared with the blank control group,the expression of PI3 K,p-mTOR/mTOR and p-Akt/Akt protein in the model control group were up-regulated,and the expression of Beclin1 protein was down-regulated,the difference between groups had statistically significance(P<0.05).Compared with the model group,the expression of p-mTOR/mTOR and p-Akt/Akt in the Taxus polysaccharide group were down-regulated,the difference between groups had statistically significance(P<0.05);while the expression of PI3 K and Beclin1 did not change significantly(P>0.05).Compared with the blank control group,the escape latency of the model control group was prolonged,and the number of crossing platform was decreased.Compared with the model group,the latency and platform retention time of the Taxus polysa-ccharide group were shortened,the number of crossing platform was increased,and the difference was statistically significant(P<0.05).CONCLUSION The application of paclitaxel can reduce neural damage,improve the memory and spatial exp
作者
陈华群
王灵俊
王锦燕
周海平
王瑶
朱慧民
CHEN Huaqun;WANG Lingjun;WANG Jinyan;ZHOU Haiping;WANG Yao;ZHOU Huimin(Department of Geriatrics,Taizhou Central Hospital-Affiliated Hospital of Taizhou University,Zhejiang Province,Taizhou 318000,China;Scientific Research Department,Taizhou Central Hospital-Affiliated Hospital of Taizhou University,Zhejiang Province,Taizhou 318000,China)
出处
《中国临床药学杂志》
CAS
2020年第4期261-266,共6页
Chinese Journal of Clinical Pharmacy
基金
台州市科学技术项目(编号2016A33701)。
