基于网络药理学探究龙血竭治疗气滞血瘀型腰椎间盘突出症的作用机制  

Investigating the mechanism of Longxue Jue in the treatment of lumbar disc herniation of the qi stagnation and blood stasis type based on network pharmacology

作　　者：陆锋 莫小汕 陀宇 LU Feng;MO Xiaoshan;TUO Yu(Department of Traditional Chinese Medicine Orthopedics,Guangxi Zhuang Autonomous Region Guidong People’s Hospital,Guangxi Zhuang Autonomous Region,Wuzhou543000,China)

机构地区：[1]广西壮族自治区桂东人民医院中医骨伤科,广西梧州543000

出　　处：《中国医药导报》2024年第29期161-167,共7页China Medical Herald

基　　金：广西壮族自治区中药管理局自筹经费科研课题(GZZC2020214)。

摘　　要：目的利用网络药理学理论探讨龙血竭治疗气滞血瘀型腰椎间盘突出症(LDH)的相关作用机制,利用动物实验进一步验证。方法通过查阅文献并结合TCMSP数据库、Pub Chem数据库和Swiss Target Prediction平台、Gene Cards数据库获得龙血竭有效活性成分治疗LDH的靶点,在DAVID数据库中进行基因本体(GO)功能和京都基因和基因组数据库(KEGG)通路富集分析,并对龙血竭关键活性成分与其对应的靶点进行分子对接验证。经过随机数字表法将48只雌雄各半大鼠分为空白组、模型组、低剂量龙血竭组(0.5 g/kg)、中剂量龙血竭组(1.0 g/kg)、高剂量龙血竭组(2.0 g/kg)和阿仑膦酸钠片组[阳性对照,7.35 mg/(kg·d)],每组8只。测定大鼠血清中的碱性磷酸酶(ALP)、骨钙素(BGP)和基质金属蛋白酶9(MMP9)水平。检测血浆黏度、红细胞电泳时间、红细胞聚集指数。结果龙血竭主要活性成分为2’-甲氧基异甘草素、Broussin、7,4’-二羟基-3’-甲氧基黄烷、龙血素B、刺干草查尔酮,治疗LDH关键靶点为Akt1、EGFR、PIK3R1、VEGFA、PIK3CA、MMP9、RAF1、HIF1A、CASP3。KEGG主要富集在Ras信号通路、Erb B信号通路等途径上。分子对接结果显示,龙血竭关键活性成分与其对应的关键靶点结合均较好。动物实验发现,与空白组比较,模型组大鼠ALP、BGP、MMP9升高(P<0.05)。与模型组比较,低、中和高剂量龙血竭组ALP、BGP和MMP9降低,且高剂量龙血竭组ALP、BGP、MMP9水平低于低剂量龙血竭组(P<0.05)。与空白组比较,模型组大鼠血浆黏度、红细胞电泳时间和红细胞聚集指数升高(P<0.05);与模型组比较,低、中和高剂量龙血竭组大鼠血浆黏度、红细胞电泳时间和红细胞聚集指数降低,且高剂量龙血竭组低于低剂量龙血竭组(P<0.05)。结论龙血竭中有效活性成分作用于多靶点、多通路,可调节炎症因子水平,改善血液流变学异常,共同发挥治疗气滞血瘀型LDH的作�Objective To explore the mechanism of Longxue Jue in the treatment of lumbar disc herniation(LDH)with qi stagnation and blood stasis by using network pharmacology theory,and to further verify it by animal experiments.Methods Through literature review and combined with TCMSP database,PubChem database,Swiss Target Prediction platform,and GeneCards database,the targets of effective active ingredients of Longxue Jue in the treatment of LDH were obtained.Gene ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were carried out in DAVID database,and molecular docking verification of key active ingredients of Longxue Jue and their corresponding targets was carried out.A total of 48 male and female rats were divided into control group,model group,low dose of Longxue Jue group(0.5 g/kg),middle dose of Longxue Jue group(1.0 g/kg),high dose of Longxue Jue group(2.0 g/kg),and Alendronate Sodium Tablets drug group(positive positive control,7.35 mg/[kg·d])by random number table method,with eight rats in each group.The levels of alkaline phosphatase(ALP),bone gla protein(BGP),matrix metalloproteinase 9(MMP9)in serum of rats were measured.Plasma viscosity,erythrocyte electrophoresis time and erythrocyte aggregation index were measured.Results The main active ingredients of Longxue Jue were 2’-methoxyisoliquiritigenin,Broussin,7,4’-dihydroxy-3’-methoxyflavan,loureirin B,and thorn hay chalcone.The key targets for the treatment of LDH were Akt1,EGFR,PIK3R1,VEGFA,PIK3CA,MMP9,RAF1,HIF1A,and CASP3.KEGG was mainly enriched in Ras signaling pathway,ErbB signaling pathway,and other pathways.The results of molecular docking showed that the key active components of Longxue Jue combined well with their corresponding key targets.Animal experiments showed that compared with blank group,ALP,BGP,and MMP9 in the model group were increased(P<0.05);compared with the model group,the levels of ALP,BGP,and MMP9 in the low,medium,and high dose Longxue Jue groups were lower,and the levels of ALP,BGP

关 键 词：网络药理学 龙血竭 腰椎间盘突出症 气滞血瘀 作用机制 

分 类 号：R996[医药卫生—毒理学] R274.9[医药卫生—药学]