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非酒精性脂肪性肝病和骨质疏松的关系及机制

The relationship and mechanism between non-alcoholic fatty liver disease and osteoporosis
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摘要 目的系统评价非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)和骨密度改变之间的相关性,同时通过生物信息学分析NAFLD和骨质疏松(osteoporosis,OP)之间的共同机制。方法检索中国知网、万方、维普数据库、PubMed、Cochrane Library、EmBase等数据库已发表的相关文献,对符合纳入标准的文献进行数据的提取,并使用Stata 15.0软件进行荟萃分析。在相关疾病数据库(Disgenet、TTD、OMIM、Gene Cards、KEGG)中筛选NAFLD和OP的相关基因,相互映射后获得疾病共同靶基因,并通过String网站和Cytoscape软件获得靶点PPI互作网络。通过CytoHubba插件获得关键基因并应用Metascape进行功能富集分析。结果本研究最终纳入8篇文献,共计纳入15095例患者,Meta分析结果显示与对照组相比,NAFLD组人群骨密度更低(SMD=-0.13,95%CI:-0.23~-0.03,P=0.002)。通过数据库检索筛选,映射出NAFLD和OP共同靶点264个,进一步筛选出核心靶点17个,富集分析发现,二者共同分子机制主要涉及HIF-1、FoxO和MAPK等信号通路。结论NAFLD与OP的发生风险增加相关,二者之间的核心靶点主要富集于调控炎症反应及糖脂代谢等信号通路上,为肝性骨病的防治及后续研究提供了新思路。 Objective To systematically evaluate the relationship between bone mineral density and non-alcoholic fatty liver disease(NAFLD),and to explore the potential co-pathogenesis of NAFLD and osteoporosis(OP)through bioinformatic analysis.Methods CNKI,WanFang,VIP database,PubMed,Cochrane Library and EmBase were searched for the relevant publications.Data were extracted from the literatures that met the requirement and were analyzed using Stata 15.0 software.NAFLD and OP related genes were gain from related disease databases(Disgenet,TTD,OMIM,Gene Cards,KEGG).After de-integration,the two groups of predicted targets were mapped to obtain common targets,and then PPI interaction network of targets was constructed through String website and Cytoscape software.Finally,CytoHubba plug-in was used to identify hub genes,and enrichment analysis was carried out through Metascape database.Results Eight studies that met the inclusion criteria were included,including 15095 patients.Meta-analysis indicated that patients with NAFLD had lower bone mineral density compared with the control group(SMD=-0.13,95%CI:-0.23--0.03,P=0.002).A total of 264 common targets were obtained and 17 key genes were screened after databases searching and filtering.Enrichment analysis of the key genes showed they mainly act on HIF-1 pathway,FoxO signaling pathway and MAPK signaling pathway,etc.Conclusion The occurrence of NAFLD is associated with an increased risk of OP.The core targets between the two are mainly enriched in the regulation of inflammatory response and glucose and lipid metabolism signaling pathways,providing new insights for the prevention and subsequent research of hepatic osteopathy.
作者 罗钒玮 刘彦均 LUO Fanwei;LIU Yanjun(The First Affiliated Hospital of Chongqing Medical University,Chongqing 400042;Department of Traditional Chinese Medicine,Dazhou Central Hospital,China)
出处 《胃肠病学和肝病学杂志》 CAS 2023年第12期1368-1373,1380,共7页 Chinese Journal of Gastroenterology and Hepatology
关键词 非酒精性脂肪性肝病 骨质疏松 META分析 生物信息学 Non-alcoholic fatty liver disease Osteoporosis Meta analysis Bioinformatics
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