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王伟伟,欧志学,章晓云,李时斌,周毅,李统.壮瑶药生骨汤治疗激素性股骨头缺血性坏死的临床疗效评价及网络药理学机制初探[J].湖南中医药大学学报英文版,2022,42(4):642-650.[Click to copy
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| 壮瑶药生骨汤治疗激素性股骨头缺血性坏死的临床疗效评价及网络药理学机制初探 |
| 王伟伟,欧志学,章晓云,李时斌,周毅,李统 |
| (广西中医药大学附属瑞康医院, 广西 南宁 530000;桂林市中医医院, 广西 桂林 541002) |
| 摘要: |
| 目的 运用Meta分析对壮瑶药生骨汤治疗激素性股骨头缺血性坏死的临床疗效进行系统评价，并运用网络药理学对其作用机制进行初探。方法 检索相关数据库，时间从建库至2021年1月，查找对象为生骨汤治疗激素性股骨头缺血性坏死的随机对照试验研究，采用RevMan 5.3软件对纳入文献进行质量评价以及Meta分析。并运用网络药理学筛选生骨汤成分、靶点以及激素性股骨头缺血性坏死靶点，进行映射，映射结果采用生物信息学进行注释，并运用分子对接技术对其进行验证。结果 （1）共纳入5篇文献，394例患者，结果提示生骨汤可显著提高临床总有效率和综合疗效评分，降低患者空骨陷窝概率。（2）网络药理学分析得到活性成分40个，共有靶点94个，关键成分为木犀草素、去甲汉黄芩素、牵牛花色素、2’-羟基染料木素、染料木素，蛋白质相互作用网络图以及关键蛋白模块图提示壮瑶药生骨汤主要通过诱导SRC、VEGFA、MMP9、PLG、MAPK14等核心靶点起到治疗作用。（3）GO、KEGG富集分析结果显示，生骨汤通过以上关键核心靶点影响PI3K/Akt、HIF-1、MAPK等主要信号通路，集中调控蛋白水解、信号传导、胶原分解代谢等生物过程来发挥治疗激素性股骨头缺血性坏死作用。（4）分子对接结果显示，关键活性成分与核心靶点结合能均小于参考值，具有较好结合活性。结论 壮瑶药生骨汤能显著提高激素性股骨头缺血性坏死患者临床总有效率和综合疗效评分，降低其空骨陷窝概率；其中木犀草素、去甲汉黄芩素、牵牛花色素、2’-羟基染料木素、染料木素等为关键活性成分，通过调节新生血管生成、凝血系统以及骨细胞的增殖、凋亡、分化等达到治疗效果。 |
| 关键词: 生骨汤 激素性股骨头缺血性坏死 Meta分析 网络药理学 分子对接 壮瑶药 |
| DOI：10.3969/j.issn.1674－070X.2022.04.021 |
| Received:April 15, 2021 |
| 基金项目:国家自然科学基金项目（81960803）；广西自然科学基金青年基金项目（2020GXNSFBA159053）；广西高校青年教师基础能力提升项目（2019KY0352）；广西中医药大学2019年校级科研课题（2019QN027）；广西中医药大学一流学科课题（2019XK026，2019XK029）；广西崇左市科技计划项目（崇科FC2019006）。 |
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| Evaluation of clinical efficacy and network pharmacology mechanism of Zhuangyao medicine Shenggu Decoction in the treatment of steroid-induced avascular necrosis of femoral head |
| WANG Weiwei,OU Zhixue,ZHANG Xiaoyun,LI Shibin,ZHOU Yi,LI Tong |
| (Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi 530000, China;Guilin Hospital of Traditional Chinese Medicine, Guilin, Guangxi 541002, China) |
| Abstract: |
| Objective To systematically evaluate the clinical efficacy of Zhuangyao medicine Shenggu Decoction in the treatment of steroid-induced avascular necrosis of femoral head by Meta analysis, and to explore its mechanism of action by network pharmacology. Methods Relevant databases were searched from the establishment of the database to January 2021, to search for randomized controlled trials of Shenggu Decoction in the treatment of steroid-induced avascular necrosis of femoral head, and RevMan 5.3 software was used to evaluate the quality of the included literature as well as Meta analysis.Network pharmacology was used to screen the components, targets of Shenggu Decoction and targets of steroid-induced avascular necrosis of femoral head, and mapped. The mapping results were annotated by bioinformatics, and verified by molecular docking technology. Results (1) A total of 5 literatures and 394 patients were included. The results indicated that Shenggu Decoction could significantly improve the clinical total effective rate and comprehensive efficacy score, and reduce the probability of patients with empty bone lacuna. (2) Network pharmacology analysis obtained 40 active ingredients, there were 94 targets in total, and the key components were luteolin, norwogonin, morning glory, 2'-hydroxygenistein, and genistein. The protein-protein interaction network map and the key protein module map suggested Zhuangyao medicine Shenggu Decoction mainly plays a therapeutic role by inducing core targets such as SRC, VEGFA, MMP9, PLG, and MAPK14. (3) The results of GO and KEGG enrichment analysis showed that Shenggu Decoction affected major signaling pathways such as PI3K/Akt, HIF-1, and MAPK through the above key core targets, and centrally regulated biological processes such as proteolysis, signal transduction, and collagen catabolism to play a role in the treatment of steroid-induced avascular necrosis of femoral head. (4) Molecular docking results showed that the binding energies of key active ingredients and core targets were all lower than the reference value, indicating good binding activity. Conclusion Zhuangyao medicine Shenggu Decoction can significantly improve the clinical total effective rate and comprehensive efficacy score in patients with steroid-induced avascular necrosis of femoral head, and reduce the probability of empty bone lacuna; luteolin, norwogonin, morning glory, 2'-hydroxygenistein, and genistein are key active ingredients, which achieve therapeutic effects by regulating angiogenesis, coagulation system, and proliferation, apoptosis, and differentiation of bone cells. |
| Key words: Shenggu Decoction steroid-induced avascular necrosis of femoral head Meta analysis network pharmacology molecular docking Zhuangyao medicine |
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