目的 本文旨在研究穿心莲内酯对慢性阻塞性肺疾病急性加重期(acute exacerbation of chronic obstructive pulmonary disease,AECOPD)患者血清学中的炎症反应因子及肺部功能改变的影响。方法 从我院已出院的患者中挑选2017年6月—2018年6月期间收治的AECOPD患者共80例,其中给予哌拉西林舒巴坦抗感染和雾化吸入布地奈德及复方异丙托溴铵治疗的患者为对照组,对照组的治疗方法基础上给予喜炎平注射液的患者为观察组,各40例。对2组患者接受治疗前后血清学中的基质金属蛋白酶-9 (matrix metalloproteinase-9, MMP-9)、降钙素原 (procalcitonin, PCT)、白介素-6 (interleukin-6, IL-6) 水平和肺功能指标等方面进行比较。结果 2组治疗前血清学MMP-9、PCT、IL-6和肺功能指标第1秒用力呼气容积(forced expiratory volume in one second, FEV1)、用力肺活量(forced vital capacity, FVC)、一秒率(FEV1/FVC)无差异(P＞0.05)。观察组经过治疗后MMP-9为(1995.13±347.281)pg/mL、IL-6为(7.98±3.23)pg/mL,低于对照组的(2159.30±367.477)pg/mL、(10.03±5.45)pg/mL(P＜0.05);观察组治疗后的PCT、FEV1、FVC和FEV1/FVC与对照组相比差异无统计学意义 (P＞0.05)。结论 穿心莲内酯在AECOPD患者中可以减少血清学中炎症因子,值得在临床中推广。
Objective To investigate the effect of andrographolide on levels of serum inflammatory factors and pulmonary function in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods Eighty patients with AECOPD who were treated in our hospital from June 2017 to June 2018 were selected. Forty patients in the control group were given anti-infection treatment with piperacillin and sulbactam and aerosol inhalation with compound ipratropium bromide and budesonide, while other 40 patients in study group were given andrographolide additionally. The levels of serum matrix metalloproteinase-9 (MMP-9), procalcitonin (PCT), interleukin-6 (IL-6) and the pulmonary function indexes of patients in the two groups were observed and compared before and after treatment. Results There were no statistically significant differences in the serum levels of MMP-9, PCT and IL-6 and the pulmonary function indexes forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and FEV1/FVC of the two groups before treatment (P>0.05). After treatment, in the study group, the MMP-9 and IL-6 levels in serum were (1995.13±347.281)pg/mL and (7.98±3.23)pg/mL respectively, which were significantly lower than that in the control group [(2159.30±367.477) pg/mL and (10.03±5.45) pg/mL (P＜0.05)].Compared with the control group, differences in the PCT, FEV1, FVC and FEV1/FVC in the study group were not statistically significant (P>0.05). Conclusion Andrographolide had significant clinical effect on the treatment of AECOPD, which could reduce the levels of serum inflammatory factors and it is worthy of clinical application.
目的 采用网络药理学方法与分子对接技术分析白头翁汤治疗细菌性痢疾（BD）的潜在活性成分与作用机制。方法 借助中药系统药理学数据库与分析平台（TCMSP）及PubChem数据库检索筛选白头翁汤方的化学成分和作用靶点，通过Uniprot数据库校正基因名，同时通过比较毒物基因组学数据库（CTD）、药物靶标数据库（TTD）、GeneCards数据库和药物和药物靶标数据库（DRUGBANK）获得BD相关疾病靶点。经在线绘图平台微生信分析“活性成分-疾病”交集靶点，使用Cyoscape 3.7.2软件构建可视化的中药-活性成分-靶点网络、蛋白质互作网络，筛选潜在的关键活性成分与核心靶点；通过Metascape数据库对进行靶点的基因本体（GO）功能分析和京都百科全书基因和基因组通路数据库（KEGG）通路富集分析，同时使用Cyoscape 3.7.2软件构建基因-通路网络，筛选潜在的通路及其作用机制。同时采用分子对接技术对白头翁汤中关键活性成分和BD核心靶点进行分析。结果 白头翁汤共筛选出266个潜在活性成分，其中，槲皮素、β-谷甾醇、异鼠李素、异延胡索单酚碱、小檗红碱、豆甾醇等66个关键活性成分可通过肿瘤坏死因子（TNF）、白细胞介素-6（IL-6）、前列腺素内过氧化物合酶2（PTGS2）、丝氨酸/苏氨酸蛋白激酶1（AKT1）、血管内皮生长因子A（VEGFA）、V-rel网状内皮细胞病毒癌基因同源物A（RELA）、半胱氨酸天冬氨酸蛋白酶3（CASP3）、白细胞介素-8（CXCL8）、白细胞介素-1B（IL-1B）、丝裂原活化蛋白激酶1（MAPK1）、白细胞介素-10（IL-10）等33个潜在交集靶点作用于BD。GO基因功能分析共得到生物过程（BP）条目20个、细胞组成（CC）条目6个、分子功能（MF）条目9个（P＜0.01），主要涉及外部凋亡过程、细胞迁移正向调控、细胞因子受体结合、蛋白同源二聚活性、TNF受体超家族结合等生物进程。KEGG通路富集分析确定13条信号通路（P＜0.01），主要涉及癌症信号通路、白细胞介素-17（IL-17）信号通路等关键通路。分子对接结果显示槲皮素、β-谷甾醇、异鼠李素、异延胡索单酚碱等核心活性成分与TNF、IL-6、PTGS2核心靶点具有良好的结合效应（结合能＜-5 kJ/mol）。结论 白头翁汤主要通过槲皮素、β-谷甾醇等潜在的多种活性成分作用于TNF、IL-6、IL-1B、PTGS2、AKT1、VEGFA等潜在的关键靶点调控IL-17等信号通路，从而发挥治疗细菌性痢疾的作用，符合中药复方多成分、多靶标、多途径起效的显著特征。
Objective To analyze the potential active ingredients and mechanism of Baitouweng Decoction in the treatment of bacillary dysentery（BD）by means of network pharmacology and molecular docking technology．Methods With the help of the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（Traditional Chinese Medicine Systems Pharmacology Database，TCMSP）and PubChem database to search and screen the chemical composition and target of Baitouweng Decoction，the gene name was corrected through the Uniprot database，and the CTD database，TTD database，GeneCards database and DRUGBANK database obtain BD-related disease targets．The intersection target was obtained through the online drawing platform，and Cytoscape 3.7.2 was used to construct a network of Pulsatilla active ingredient-component disease intersection target．The protein-protein interaction analysis of the intersection target was performed through the String database，and the Cytoscape 3.7.2 software was used for visualization．The Metascape database platform performed GO function analysis and KEGG pathway enrichment analysis on the target to predict its mechanism of action．The key active ingredient compounds in Baitouweng Decoction were molecularly docked with the core protein in the intersection target．Results A total of 266 potential active ingredients in Baitouweng Decoction were screened，of which 66 key active ingredients such as quercetin，β-sitosterol，isorhamnetin，Isocorypalmine，berberine，stigmasterol，etc．It acts on BD through 33 potential intersection targets such as TNF，IL-6，PTGS2，AKT1，VEGFA，RELA，CASP3，CXCL8，IL-1B，MAPK1，IL-10．GO gene function analysis yielded a total of 20 biological process（BP）entries，6 cell composition（CC）entries，and 9 molecular function（MF）entries（P＜0.01），which mainly involve external apoptosis process and positive regulation of cell migration，Cytokine receptor binding，protein homodimerization activity，tumor necrosis factor receptor superfamily binding and other biological processes．KEGG pathway enrichment analysis identified 13 signal pathways（P＜0.01），mainly related to key pathways such as cancer signal pathway and IL-17 signal pathway．The results of molecular docking showed that the core active ingredients such as quercetin，β-sitosterol，isorhamnetin，Isocorypalmine and TNF，IL-6，PTGS2 core targets have good binding effects（binding energy ＜-5 KJ /mol）．Conclusions Baitouweng Decoction modulated signaling pathways involving IL-17 through its active constituents like quercetin and β-sitosterol，targeting key molecules such as TNF，IL-6，IL-1β，PTGS2，AKT1，and VEGFA，reflecting the multi-target therapeutic approach of traditional Chinese medicine．
