摘要
目的探讨丹玄口康治疗口腔黏膜下纤维化(oral submucosal fibrosis,OSF)的作用网络和药效机制。方法基于网络药理学的方法,结合TCMSP、UniProt、GeneCards等数据库联合分析丹玄口康的有效成分和OSF的作用靶点;通过Cytoscape构建有效成分与靶基因的网络,对靶基因进行GO富集分析和信号通路分析;依据网络药理学结果,设置每组10只共5组SD大鼠进行实验论证,包括正常对照组、模型组、丹玄口康低剂量组、丹玄口康中剂量组、丹玄口康高剂量组。除正常对照组外,其余组以槟榔碱对口腔黏膜机械刺激和注射造模。模型组和正常对照组予以生理盐水灌胃,丹玄口康低、中、高剂量组分别以4、8、12 mL/kg浓度的中药灌胃,每天灌胃1次,连续8周。HE观察大鼠口腔黏膜的病理变化,q-PCR检测HIF-1α的含量。结果丹玄口康的主要活性成分93个,包括丹参酮、芍药苷、黄芩素等;治疗OSF的关键靶基因有48个,包括EGFR、JUN、HIF-1α等,通过参与氧化应激进程和HIF-1信号通路等,发挥治疗OSF的作用。动物实验结果显示:丹玄口康能改善OSF大鼠口腔黏膜上皮萎缩和胶原沉积,同时能下调HIF-1α的转录(P<0.01)。结论丹玄口康治疗OSF体现了中药多成分、多靶点和多通路的作用特点。
Objective To investigate the network and pharmacodynamic mechanism of Danxuankoukang in treating oral submucosal fibrosis(OSF).Methods Based on network pharmacology,TCMSP,UniProt,Genecards and other databases were combined to analyze the effective components of Danxuankoukang and the action targets of OSF;a network of active ingredients and target genes was constructed through Cytoscape,and GO enrichment analysis and signaling pathway analysis on target genes were performed;according to the results of network pharmacology,a total of 5 groups with 10 SD rats in each group were set up for experimental demonstration,including control group,model group,Danxuankoukang low-dose group,Danxuankoukang medium-dose group and Danxuankoukang high-dose group.Except the control group,the other groups were made by mechanical stimulation and injection of arecoline to oral mucosa.The model group and the control group were given physiological saline by gavage,and the low-dose,medium-dose and high-dose groups of Danxuankoukang were given 4,8 and 12 mL/kg concentrations of traditional Chinese medicine by gavage,once a day for 8 weeks.Pathological changes of rat oral mucosa were observed by HE,and the content of HIF-1αwas detected by q-PCR.Results There were 93 main active components in Danxuankoukang,including tanshinone,paeoniflorin and baicalin;there were 48 key target genes in the treatment of OSF,including EGFR,JUN,HIF-1αand other targets,which play a role in the treatment of OSF through oxidative stress response and HIF-1 signaling pathway.The results of animal experiments showed that Danxuankoukang can improve oral mucosa epithelial atrophy and collagen fiber deposition in OSF rats,and regulate HIF-1αtranscription(P<0.01).Conclusion The study shows the characteristics of multi components,multi targets and multi pathways of traditional Chinese medicine.
作者
朱可可
周蓉
王志豪
谭劲
ZHU Keke;ZHOU Rong;WANG Zhihao;TAN Jin(The First Hospital of Hunan University of Chinese Medicine,Changsha,Hunan 410007,China;Changsha Maternal and Child Health Care Hospital,Changsha,Hunan 410008,China)
出处
《湖南中医药大学学报》
CAS
2022年第9期1485-1492,共8页
Journal of Hunan University of Chinese Medicine
基金
国家自然科学基金面上项目(NSFC81874496)
湖南省中医药管理局重点项目(201808)
湖南省中医药管理局优秀青年项目(2021240)。
关键词
丹玄口康
口腔黏膜下纤维化
网络药理学
靶点
通路
Danxuankoukang
oral submucosal fibrosis
network pharmacology
target
pathway
