基于PI3K/Akt/FoxO3a信号通路探讨壮骨止痛胶囊防治肌少-骨质疏松症的作用机制  

Mechanism of Zhuanggu Zhitong Capsule in Preventing and Treating Osteosarcopenia Based on PI3K/Akt/FoxO3a Signaling Pathway

作　　者：桑继亮 杨岩冰 马江涛 柴爽 叶茂林[2] SANG Jiliang;YANG Yanbing;MA Jiangtao;CHAI Shuang;YE Maolin(Kaifeng Second Hospital of Chinese Medicine of Henan Province,Kaifeng 475000,China;Luoyang Orthopedic-Traumatological Hospital of Henan Province(Henan Provincial Orthopedic Hospital),Zhengzhou 450046,China;Guangzhou University of Chinese Medicine,Guangzhou 510405,China)

机构地区：[1]河南省开封市第二中医院,河南开封475000 [2]河南省洛阳正骨医院(河南省骨科医院),河南郑州450046 [3]广州中医药大学,广东广州510405

出　　处：《中医药信息》2022年第10期19-27,共9页Information on Traditional Chinese Medicine

基　　金：河南省自然科学基金青年科学基金项目(202300410555)。

摘　　要：目的:通过网络药理学联合动物实验的方法,预测并证实壮骨止痛胶囊防治肌少-骨质疏松症(OS)的作用机制。方法:首先利用网络药理学方法筛选壮骨止痛胶囊的有效成分及靶点和OS的靶点,将筛选出的关键靶点进行GO和KEGG富集分析。采用去势+地塞米松腹腔注射方法建立OS大鼠模型,灌胃壮骨止痛胶囊水溶液,观察用药后大鼠体质量、骨密度、前肢抓力、骨骼肌质量指数、四肢骨骼肌质量指数以及PI3K/Akt/FoxO3a信号通路相关蛋白的变化情况。结果:壮骨止痛胶囊防治OS的关键通路主要有PI3K/Akt信号通路、叉头转录因子信号通路和肿瘤坏死因子信号通路等。动物实验表明,去势+地塞米松腹腔注射可造成大鼠全身骨密度、腰椎骨密度、前肢抓力、骨骼肌质量指数和四肢骨骼肌质量指数下降(P<0.05)。壮骨止痛胶囊可明显提高大鼠全身骨密度、腰椎骨密度、前肢抓力、骨骼肌质量指数和四肢骨骼肌质量指数,并增加PI3K、p-Akt和p-FoxO3a蛋白表达(P<0.05)。结论:去势+地塞米松腹腔注射可成功构建OS大鼠模型,壮骨止痛胶囊防治OS的作用机制与上调PI3K/Akt/FoxO3a信号通路密切相关。Objective:To predict and confirm the mechanism of Zhuanggu Zhitong Capsule(ZGZT)in preventing and treating osteosarcopenia(OS)based on network pharmacology combined with animal experiments.Methods:Network pharmacology was used to screen the effective ingredients and targets of ZGZT and the targets of OS.The key targets were screened,and the enrichment analysis of GO and KEGG were conducted.The rat model of OS was established with ovariectomy and intraperitoneal injection of Dexamethasone.After the administration of ZGZT aqueous solution,body mass,bone mineral density(BMD),grasping force of forelimbs,skeletal muscle index(SMI),appendicular skeletal muscle mass(ASMM),as well as PI3K/Akt/FoxO3a signaling pathway related protein changes were observed in the rats.Results:The key pathways of ZGZT in the prevention and treatment of OS mainly included PI3K/Akt signaling pathway,FOXO signaling pathway and TNF signaling pathway.Animal experiments showed that ovariectomy plus Dexamethasone intraperitoneal injection could reduce the whole body BMD and lumbar bone BMD,the grip strength of forelimbs,SMI and ASMM(P<0.05).ZGZT significantly increased the whole body BMD and lumbar bone BMD,the grip strength of forelimbs,SMI and ASMM,as well as the protein expressions of PI3K,p-Akt and p-FoxO3a(P<0.05).Conclusion:Ovariectomy plus Dexamethasone intraperitoneal injection can successfully construct OS rat model.The mechanism of ZGZT in preventing and treating OS is closely related to the up-regulation of PI3K/Akt/FoxO3a signaling pathway.

关 键 词：壮骨止痛胶囊 肌少-骨质疏松症 大鼠模型 PI3K/Akt/FoxO3a 

分 类 号：R285.5[医药卫生—中药学]