藁本内酯调控H型血管防治骨质疏松症的网络药理学与分子对接分析及动物实验研究  

Network pharmacology and molecular docking analysis and animalexperimental study of ligustilide regulating H-type blood vessels inprevention and treatment of osteoporosis

作　　者：王凯 文皓楠 宋志靖 宋永嘉 宋敏 WANG Kai;WEN Hao-nan;SONG Zhi-jing;SONG Yong-jia;SONG Min(Dept of Orthopaedics,Gansu Provincial Hospital,Gansu University of Chinese Medicine,Lanzhou 730000,China;Clinical College of Chinese Medicine,Gansu University of Chinese Medicine,Lanzhou 730000,China)

机构地区：[1]甘肃省人民医院骨科,甘肃兰州730000 [2]甘肃中医药大学中医临床学院,甘肃兰州730000

出　　处：《中国药理学通报》2025年第3期583-591,共9页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81960877);甘肃省自然科学基金资助项目(No 24JRRA1063,22JR11RA132);甘肃省教育厅重大产业支撑项目(No 2022CYZC-52);兰州市科技计划项目(No 2024-4-33);甘肃省人民医院院内科研基金项目(No 24GSSYA-7)。

摘　　要：目的基于网络药理学与分子对接技术探讨藁本内酯调控H型血管防治骨质松疏松症的生物学机制,并结合动物实验进行验证。方法网络药理学预测藁本内酯调控H型血管防治骨质疏松症的可能机制,分子对接验证核心靶标EGFR与藁本内酯的结合能力。建立骨质疏松大鼠模型,分为假手术组、模型组、藁本内酯高、中、低剂量(80、40、20 mg·kg^(-1))组,HE染色观察股骨组织病理改变,免疫荧光检测胫骨干骺端CD31、EMCN、OSX+、RUNX2+蛋白表达,Western blot检测p-EGFR、p-PI3K、p-Akt蛋白表达。结果网络药理学结果显示,共得到20个交集靶点,EGFR、PTGS2、ESR1、ICAM1等属于核心靶标,分子对接显示EGFR与藁本内酯具有强烈的结合力。藁本内酯通过调控H型血管表达防治骨质疏松症的信号通路主要富集在PI3K-Akt、TNF等。与模型组比较,藁本内酯能明显增加骨小梁数量,改善骨微结构的破坏;明显提高CD31、EMCN、OSX+、RUNX2+蛋白表达(P<0.01,P<0.05),促进H型血管的生成,提高p-EGFR、p-PI3K、p-Akt蛋白表达(P<0.01,P<0.05)。结论藁本内酯能增加去势大鼠骨组织H型血管的表达,减轻骨小梁的破坏、改善骨微结构,EGFR介导的PI3K/Akt信号通路可能是其发挥生物学效应的关键途径。Aim To explore the biological mechanism of ligustilide in the prevention and treatment of osteoporosis by regulating H-type blood vessels,combined with animal experiments for verification,based on network pharmacology and molecular docking technology Methods The possible mechanism of ligustilide regulating H-type blood vessels to prevent osteoporosis was predicted by network pharmacology.Molecular docking technology was used to verify the binding ability of the core target EGFR to ligustilide.The rat model of osteoporosis was established and divided into the sham group,model group,ligustilide high,medium and low dose(80,40,20 mg·kg^(-1))groups.The pathological changes of femur were observed by HE staining.The expressions of CD31,EMCN,OSX+and RUNX2+protein in tibial metaphysis were detected by immunofluorescence.The expression of p-EGFR,p-PI3K and p-Akt protein was detected by Western blot.Results The results of network pharmacology showed that a total of 20 intersection targets were obtained.EGFR,PTGS2,ESR1 and ICAM1 were core targets,and molecular docking showed that EGFR had a strong binding ability with ligustilide.The signaling pathways of ligustilide in the prevention and treatment of osteoporosis by regulating the expression of H-type blood vessels were mainly enriched in PI3K-Akt,TNF,etc.Compared with the model group,ligustilide could significantly increase the number of trabecular bone and improve the destruction of bone microstructure.The expression of CD31,EMCN,OSX+and RUNX2+significantly increased(P<0.01,P<0.05),the formation of H-type blood vessels were promoted,and the expression of p-EGFR,p-PI3K and p-Akt significantly increased(P<0.01,P<0.05).Conclusions Ligustilide can increase the expression of H-type blood vessels in bone tissue of osteoporosis model rats,reduce the damage of bone trabecula and improve bone microstructure effectively.EGFR-mediated PI3K/Akt signaling pathway may be the key way to exert its biological effects.

关 键 词：骨质疏松症 藁本内酯 H型血管 EGFR PI3K/AKT信号通路 分子机制 

分 类 号：R-332[医药卫生] R284.1R322.12R319R336R681