摘要
目的:采用网络药理学方法预测桃红四物汤促进股骨干骨折愈合的药效物质基础及作用靶点,并建立右侧股骨干骨折大鼠模型对关键靶点进行验证。方法:通过TCMSP数据库筛选桃红四物汤的化合物及其作用靶点;使用GeneCards数据库获得股骨干骨折的疾病靶点;采用Cytoscape 3.6.0软件构建“药物-成分-基因-疾病”网络;通过STRING数据库建立靶蛋白交互作用(PPI)网络并分析核心靶点。使用多个剂量桃红四物汤干预右侧股骨干骨折大鼠对核心靶点进行初步验证,通过HE染色法观察桃红四物汤对骨折愈合的影响,利用Western blotting技术检测骨折早期骨痂内核心靶点蛋白的表达情况。结果:筛选后获得14个活性成分,共对应28个靶点。PPI网络分析发现VEGF节点度值最大,为潜在的核心靶点;通过分子对接技术分析可知黄芩苷、β-胡萝卜素可能为靶向VEGF的关键活性化合物。动物实验验证发现,桃红四物汤早期干预后,大鼠股骨干骨折端骨痂成骨进程加快,软骨细胞大量凋亡,成骨细胞不断增加,骨基质分泌增多且钙化加强,并以桃红四物汤高剂量组为佳。VEGF蛋白表达结果表明,与模型组比较,桃红四物汤中、高剂量组大鼠早期骨痂内VEGF蛋白相对表达量均明显升高(P<0.05),其中高剂量桃红四物汤作用最为显著;桃红四物汤低剂量组大鼠早期骨痂内VEGF蛋白相对表达量与模型组比较,差异无统计学意义(P>0.05)。结论:VEGF为桃红四物汤促进股骨干骨折愈合的核心靶点,黄芩苷和β-胡萝卜素可能靶向VEGF为桃红四物汤促进股骨干骨折愈合的关键活性成分。
Objective:To predict the effective components and potential targets of Taohong Siwu decoction in promoting femoral shaft fracture healing based on the network pharmacology,and to verify the key molecular target in a rat model of right femoral shaft fracture.Methods:The active components and potential targets in Taohong Siwu decoction were obtained from the TCMSP database,and the related targets of femoral shaft fracture were identified from GeneCards database.The"drug-component-gene-disease"network was established by Cytoscape 3.6.0 software,and PPI network was constructed by using STRING database to analyze the key target.A key target was preliminarily confirmed in right femoral shaft fracture rats intragastric administration with different doses of Taohong Siwu decoction.HE staining was used to observe the effect of Taohong Siwu decoction on fracture healing.Western blotting was used to detect the expression of the protein in callus at the early stage of fracture.Results:A total of 14 active components of Taohong Siwu decoction in treatment of femoral shaft fracture were obtained,corresponding to 28 targets.According to PPI network,VEGF showed the highest node degree,which was regarded as a potential key molecular target.Baicalin andβ-carotene may be the key active compounds targeting VEGF by molecular docking technology.According to experiment,after the early intervention of Taohong Siwu decoction,the bone formation process of the callus at the fracture end of the femoral shaft was accelerated in rats,and a large number of chondrocytes were apoptotic.Osteoblasts were continuously increasing.Bone matrix secretion was increased,and calcification was strengthened.The high-dose group of Taohong Siwu decoction is better.According to VEGF protein expression results,compared with the model group,the relative expression of VEGF protein increased in the low,medium and high dose groups of Taohong Siwu decoction group,and the relative expression of VEGF protein was the most obvious in the high dose group of Taohong Siwu
作者
马泽冰
李汪洋
熊辉
MA Zebing;LI Wangyang;XIONG Hui(The Second Affiliated Hospital of Hunan University of Chinese Medicine,Changsha Hunan 410007 China;Hunan University of Chinese Medicine,Changsha Hunan 410208,China;Orthopaedics&Traumatology of Chinese Medicine of Hunan Medical Research Center,Changsha Hunan 410007,China)
出处
《中医药导报》
2023年第10期23-29,49,共8页
Guiding Journal of Traditional Chinese Medicine and Pharmacy
基金
国家自然科学基金面上项目(81874478)
湖南省中医药管理局一般项目(2022-04033025)
湖南省教育厅青年项目(22B0369)。
关键词
股骨干骨折
骨折愈合
桃红四物汤
网络药理学
靶点
大鼠
femoral shaft fracture
fracture healing
Taohong Siwu decoction
network pharmacology
target
rat
