基于网络药理学和Meta分析的清开灵注射剂作用机制与临床应用研究
发布时间：2018-07-24 16:20
【摘要】：清开灵注射剂目前有清开灵注射液和注射用清开灵(冻干)两个品种,均主要由胆酸、猪去氧胆酸、水牛角、黄芩苷、栀子、金银花、板蓝根、珍珠母组成,功效为清热解毒、化痰通络、醒神开窍,具有抗菌、抗病毒、解热、抗炎、免疫调节、保肝及改善脑循环、保护脑细胞功能等多种药理作用。清开灵注射剂临床应用广泛,尤其在脑血管疾病、上呼吸道感染、肝炎、高热等方面具有良好的疗效。清开灵注射剂的药效物质基础、作用机制及临床评价研究一直是学术界的研究热点。本研究基于网络药理学的研究方法,利用"药物-成分-靶标-疾病"多层次生物网络,结合基因功能注释和KEGG通路,开展清开灵注射剂的作用机制研究;基于Meta分析和系统评价的循证医学手段,科学地评估各项临床随机对照试验的方法学质量和相关数据,为清开灵注射剂治疗特定疾病提供更加可靠的证据,以供临床参考。研究目的1探讨清开灵注射剂的药理作用机制,从微观角度揭示清开灵注射剂药理作用特点。2系统评价清开灵注射剂治疗急性上呼吸道感染、肺炎、流行性腮腺炎的临床疗效及安全性。研究方法(一)网络药理学利用公共数据库(如TCMSP、PubChemCompound和TCMID)收集清开灵注射剂的成分及其分子信息,结合药物分子的ADME性质参数及文献研究,预测和筛选活性分子,并获取其靶标、基因及疾病信息,利用Microsoft Access 2010构建数据库;提取数据,利用Cytoscape 3.4.0软件构建"药物-成分-靶标-疾病"网络图,进行网络拓扑学分析,确定网络关键节点或关键模块,再通过GO功能富集分析和KEGG通路富集分析,分析其基因集合的主要功能,多层次、多角度探讨清开灵注射剂的作用机制。(二)Meta 分析通过全面检索国内外文献数据库,包括中国知网、万方、维普、SinMed、PubMed、Springer、Web of Science、Cochrane Central Register of Controlled Trials 等,收集清开灵注射剂治疗特定疾病的临床随机对照试验(RCTs),纳入符合标准的RCTs,并对其进行质量评价和资料提取;对同质性较好的研究进行Meta分析,以森林图呈现结果;异质性较大时可采用Meta回归、亚组分析、敏感性分析探讨异质性来源,采用敏感性分析检验结果的稳定性,以漏斗图检测发表偏倚。研究结果(一)基于网络药理学的作用机制研究1数据库构建:所构建的"清开灵注射剂网络药理学基础信息数据库"包含清开灵注射剂的8个药物所涉及的116个成分,1 271个靶标,929种疾病,以及3 786条成分、靶标、疾病对应关系。2清开灵注射剂作用机制的拆方分析研究:(1)"胆酸-猪去氧胆酸"作用机制研究:主要成分胆酸、猪去氧胆酸均具有较好的类药性;该药对的"药物-成分-靶标-疾病"网络涉及6个靶标和8种疾病,以盐皮质激素受体(MR)和肝X受体(LXRα、LXRβ)为关键靶标,主要涉及脑损伤、动脉粥样硬化、血脂异常等疾病;GO富集主要在甘油三酯的合成、胆固醇的储存及流出调控等生物学过程方面,KEGG通路主要富集在胰岛素抵抗通路等。(2)"水牛角-珍珠母"作用机制研究:共筛选出6个成分,其总体类药性较好;该药对的"药物-成分-靶标-疾病"网络涉及765个靶标和595种疾病,以前列腺素内过氧化物合酶2(COX-2)和过氧化物酶体增殖物激活受体γ(PPARγ)为关键靶标,以精神分裂症、阿尔茨海默症和炎症为度值最高的疾病;GO富集主要在小分子代谢、细胞代谢等生物学过程方面,KEGG通路主要富集在多种氨基酸代谢通路中。(3)"黄芩苷-栀子"作用机制研究:共筛选出20个成分,其总体类药性较好;该药对的"药物-成分-靶标-疾病"网络涉及198个靶标和369种疾病,以COX-2、PPARy和5-脂氧合酶(5-LOX)等为关键靶标,疾病主要涉及肿瘤、糖尿病、心血管疾病等;GO富集主要在化学刺激响应、细胞增殖调控、细胞凋亡及细胞程序性死亡调控等生物学过程方面,KEGG通路主要富集在多种癌症通路和乙型肝炎通路等。(4)"金银花-板蓝根"作用机制研究:共筛选出92个成分,其总体类药性较好;该药对的"药物-成分-靶标-疾病"网络涉及665个靶标和609种疾病,以COX-2、热休克蛋白90α(HSP86)、前列腺素内过氧化物合酶1(COX-1)和PPARγ等为关键靶标,疾病主要涉及肿瘤、心血管疾病、糖尿病、阿尔茨海默症、炎症等;GO富集主要在细胞表面受体相关信号通路、化学刺激响应等生物学过程方面,KEGG通路主要富集在cAMP信号通路、钙离子信号通路、多种癌症通路及乙型肝炎通路等。3清开灵注射剂作用机制的整体研究:共筛选出116个成分,其总体类药性较好;清开灵注射剂的"药物-成分-靶标-疾病"网络涉及1 271个靶标和929种疾病,以COX-2、HSP86、COX-1靶标度值最高,主要涉及肿瘤、心血管疾病、糖尿病、阿尔茨海默症、精神分裂症、炎症等疾病;GO富集主要在化学刺激响应、信号传递、代谢过程等生物学过程方面,KEGG通路主要富集在cAMP信号通路、cGMP-PKG信号通路、多种氨基酸代谢通路、癌症通路和乙型肝炎通路等;模块分析所得6个模块对应基因的GO富集主要在心率调控、心肌收缩调控等生物学过程中,KEGG通路主要富集在心肌细胞肾上腺素信号通路和cGMP-PKG信号通路等;具有血脑屏障通透性的29个成分对应基因的GO富集主要在胆固醇代谢过程、胆固醇体内平衡等生物学过程中,KEGG通路主要富集在PPAR信号通路、多种氨基酸的合成通路及尼古丁成瘾通路等。(二)基于Meta分析的临床评价研究1清开灵注射剂治疗急性上呼吸道感染:纳入42项研究,累计患者5 905例;在单用或联合西医对症治疗基础上,清开灵注射剂在提高急性上呼吸道感染的临床疗效总有效率方面优于利巴韦林注射剂(RR=1.19,95%CI:1.16～1.22,P0.000 01)等;12项研究累计报告试验组42例药品不良反应/不良事件(ADRs/ADEs),11项研究累计报告对照组34例ADRs/ADEs。2清开灵注射剂治疗肺炎:纳入17项研究,累计患者1 702例;在应用抗生素和对症治疗基础上,联用清开灵注射剂可提高治疗肺炎的临床疗效总有效率(RP= 1.23,95%CI:1.14～1.33,P0.000 01)等;4 项研究累计报告试验组 27 例 ADRs/ADEs,对照组64例ADRs/ADEs。3清开灵注射剂治疗流行性腮腺炎:纳入7项研究,累计患者580例;清开灵注射剂联合对症治疗在缩短流行性腮腺炎的退热时间方面优于利巴韦林注射剂联合对症治疗或仅对症治疗(MD =-1.16,95%CI:-1.36～-0.96,P0.000 01)等;3项研究未发生ADRs/ADEs,4项研究未报告ADRs/ADEs。研究结论1清开灵注射剂各药对的网络关键节点分析、基因GO功能注释和KEGG通路富集分析的结果各有侧重,反映了清开灵注射剂各药对之间功效的差异及各药对之间作用机制方面的相互配合,体现了中医配伍用药和复方用药的意义。2清开灵注射剂可能由多个成分通过作用于LXR、COX-2、HSP86和PPARγ等关键靶标,调控胆固醇代谢与其体内平衡、氨基酸代谢、细胞增殖及细胞凋亡等多个生物学过程,参与多个信号通路、代谢通路和癌症等疾病通路,在肿瘤、心血管疾病、糖尿病、阿尔茨海默症、精神分裂症及炎症等疾病中发挥作用。3清开灵注射剂临床主要用于脑血管疾病,用于心血管疾病治疗的报道较少,但本研究发现其多个作用靶标、相关通路与心肌梗死、缺血性心脏病等心血管疾病密切相关,值得进一步深入研究。4清开灵注射剂各药对及其整体处方的"药物-成分-靶标-疾病"网络均具有部分无标度和小世界特性,模块属性很低,适宜采用识别关键节点的方法进行网络分析,模块分析的方法根据具体情况可以选用。5在临床应用方面,相较于仅采用西医常规治疗或对症治疗,联合清开灵注射剂可以提高急性上呼吸道感染、肺炎和流行性腮腺炎的治疗效果。但是本研究通过纳入文献的分析,在清开灵注射剂的安全性方面尚无法给出确切结论。
[Abstract]:Qingkailing injection has two varieties of Qingkailing injection and injection Qingkailing (freeze-dried), which are mainly composed of cholic acid, porcine deoxycholic acid, water ox horn, baicalin, gardenia, honeysuckle, Radix Isatidis root, pearl mother. The effect is clearing heat and detoxifying, removing phlegm and dredging collaterals, opening the orifices, antivirus, antipyretic, anti-inflammatory, immune regulation, liver preservation and improvement. Qingkailing injection has a wide range of clinical applications, especially in cerebrovascular disease, upper respiratory tract infection, hepatitis, high fever and so on. The pharmacological basis, mechanism and clinical evaluation of Qingkailing injection have always been a hot topic in the academic field. In the study of network pharmacology, the mechanism of the action mechanism of Qingkailing injection was studied by using the multilevel biological network of "drug component - target disease", combined with gene functional annotation and KEGG pathway, and based on the evidence-based medical methods of Meta analysis and systematic evaluation, the methodological quality and phase of various clinical randomized controlled trials were evaluated scientifically. To provide more reliable evidence for the treatment of specific diseases by Qingkailing injection for clinical reference. Objective 1 to explore the pharmacological mechanism of Qingkailing injection and to reveal the pharmacological and functional characteristics of Qingkailing injection from the microcosmic point of view.2 system evaluation of Qingkailing injection for the treatment of acute upper respiratory infection, pneumonia, and epidemic parotid gland. The clinical efficacy and safety of inflammation. (I) network pharmacology uses public databases (such as TCMSP, PubChemCompound and TCMID) to collect the components and molecular information of Qingkailing injection, combined with the ADME properties and literature research of drug molecules, to predict and screen the active molecules, and to obtain their targets, gene and disease information, and use M Icrosoft Access 2010 constructs the database, extracts the data, uses the Cytoscape 3.4.0 software to construct the "drug component target disease" network map, carries out network topology analysis, determines the network key nodes or key modules, and then analyzes the main functions of the gene collection by GO function enrichment analysis and KEGG pathway enrichment analysis, and the multilevel and multi angle analysis. The effect mechanism of Qingkailing injection was discussed. (two) Meta analysis through the comprehensive retrieval of domestic and foreign literature database, including China know net, Wanfang, VP, SinMed, PubMed, Springer, Web of Science, Cochrane Central Register of Controlled, collect the clinical randomized controlled trial of Qingkailing injection for the treatment of specific diseases. The quality evaluation and data extraction were included in the standard RCTs, and Meta analysis was carried out for better homogeneity research. The result of forest map was presented. Meta regression, subgroup analysis, sensitivity analysis were used to investigate the heterogeneity, and sensitivity analysis was used to test the stability of the results. 1 database construction based on network pharmacology: the construction of "Qingkailing injection network pharmacology basic information database" contains 116 components, 1271 targets, 929 diseases, 3786 components, target, and disease correspondence.2 Qingkailing for the 8 drugs of Qingkailing injection network pharmacology. Analysis and Study on the mechanism of the action of injections: (1) the mechanism of the action of cholic acid - porcine deoxycholic acid: the main component of cholic acid, porcine deoxycholic acid has a better class property; the drug - drug - ingredient - target - disease network involves 6 targets and 8 diseases, and the key target is the MR and the liver X receptor (LXR a, LXR beta). Mainly related to brain injury, atherosclerosis, dyslipidemia and other diseases, GO enrichment mainly in the synthesis of triglycerides, cholesterol storage and regulation of biological processes, the KEGG pathway is mainly enriched in the insulin resistance pathway. (2) the "water cow angle pearl mother" mechanism: a total of 6 components, its overall drug resistance Well, the drug's "drug - component - target - disease" network involves 765 targets and 595 diseases, with prostaglandin endogenous peroxidase 2 (COX-2) and peroxisome proliferator activated receptor gamma (PPAR gamma) as the key target, with schizophrenia, Alzheimer's disease and inflammation as the highest degree of disease; GO enrichment is mainly in small molecular generations. KEGG pathway is mainly enriched in a variety of amino acid metabolic pathways. (3) the mechanism of "baicalin - Gardenia" is studied: a total of 20 components are screened, and their overall drug resistance is better; the drug "drug component target disease" network involves 198 targets and 369 diseases, with COX-2, PPARy, and 5- lipoxygenase. 5-LOX) and so on as the key target, the disease mainly involves tumor, diabetes, cardiovascular disease and so on. The enrichment of GO is mainly in the biological process of chemical stimulation response, cell proliferation regulation, cell apoptosis and programmed cell death regulation. The KEGG pathway is mainly enriched in many kinds of cancer pathways and hepatitis B pathway. (4) "honeysuckle isatis root" effect Mechanism study: a total of 92 components were screened, and their overall drug class was better; the drug "drug component target disease" network involved 665 targets and 609 diseases, with COX-2, heat shock protein 90 alpha (HSP86), prostaglandin synthase 1 (COX-1) and PPAR gamma as the key targets, and the disease mainly involved tumor, cardiovascular disease, diabetes, Alzheimer's disease, inflammation and so on; GO enrichment mainly in the cell surface receptor related signaling pathway, chemical stimulation response and other biological processes, the KEGG pathway is mainly enriched in the cAMP signal pathway, calcium signal pathway, various cancer pathways and hepatitis B pathway and other.3 Qingkailing injection mechanism of the overall study: a total of 116 COX-2, HSP86, COX-1 target value is the highest, mainly involving tumor, cardiovascular disease, diabetes, Alzheimer's disease, Alzheimer's disease, semen schizophrenia, inflammation and other diseases; GO enrichment mainly in chemical stimulation response, letter KEGG pathway is mainly enriched in cAMP signaling pathway, cGMP-PKG signaling pathway, multiple amino acid pathway, cancer pathway and hepatitis B pathway, and the GO enrichment of the 6 module corresponding genes is mainly in biological processes such as heart rate regulation, myocardial contraction regulation and other biological processes, KEGG pathway. The epinephrine signaling pathway and cGMP-PKG signaling pathway are mainly enriched in the cardiac myocytes; the GO enrichment of the 29 components corresponding to the permeability of the blood brain barrier is mainly in the biological process of cholesterol metabolism and cholesterol balance, and the KEGG pathway is mainly enriched in the PPAR signaling pathway, the synthesis pathway of various amino acids and the NiO Ding Chengyin pathway, etc. (two) clinical evaluation based on Meta analysis 1 Qingkailing Injection in the treatment of acute upper respiratory tract infection: 42 studies and 5905 cumulative patients; on the basis of single use or combined treatment of Western medicine, the total effectiveness of Qingkailing Injection in improving the clinical efficacy of acute upper respiratory infection is superior to Leigh Bhave Lin. Injection (RR=1.19,95%CI:1.16 ~ 1.22, P0.000 01), 12 studies reported 42 cases of adverse drug reactions / adverse events (ADRs/ADEs) in the experimental group, and 11 studies reported 34 cases of ADRs/ADEs.2 Qingkailing injection for pneumonia in the control group: 17 studies were included in 1702 cases, combined with antibiotics and symptomatic treatment. Qingkailing injection could improve the total effective efficiency of the treatment of pneumonia (RP= 1.23,95%CI:1.14 ~ 1.33, P0.000 01), 4 studies reported 27 cases of ADRs/ADEs in the experimental group and 64 cases of ADRs/ADEs.3 Qingkailing Injection in the control group for the treatment of epidemic parotitis: 7 studies, 580 cases of cumulative patients, and Qingkailing Injection combined with symptomatic treatment. The time of reducing the fever of epidemic parotitis was better than that of Leigh Bhave Lin injection combined with symptomatic treatment or only symptomatic treatment (MD =-1.16,95%CI:-1.36 to -0.96, P0.000 01); 3 studies did not occur ADRs/ADEs, 4 studies did not report ADRs/ADEs. study conclusion 1 the key node analysis of each drug pair of Qingkailing injection, gene GO function injection. The results of the analysis of the concentration and analysis of the KEGG pathway were focused, reflecting the differences in the efficacy of each drug and the interaction between the drugs and the mechanism of the action between each drug, reflecting the significance of the combination of medicine and compound medicine of traditional Chinese medicine (.2), the key of the Qingkailing injection may be affected by many components through the action on LXR, COX-2, HSP86 and PPAR gamma. Target, regulation of cholesterol metabolism and its internal balance, amino acid metabolism, cell proliferation, cell apoptosis and other biological processes involved in multiple signaling pathways, metabolic pathways and cancer pathways, and play a role in.3 injection in diseases such as tumors, cardiovascular diseases, diabetes, Alzheimer's disease, schizophrenia and inflammation. The drug is mainly used in cerebrovascular disease, and there are few reports on the treatment of cardiovascular diseases. However, this study found that many target targets, related pathways are closely related to myocardial infarction, ischemic heart disease and other cardiovascular diseases. It is worthwhile to further study the "drug composition target disease" and the overall prescription of.4 Qingkailing injection. The disease "network has a part of scale-free and small world characteristics, the module attribute is very low, the method of identifying key nodes is suitable for network analysis. The method of module analysis can choose.5 in clinical application according to the specific situation, compared with only conventional treatment of Western medicine or symptomatic treatment, combined with Qingkailing injection can improve the acute effect. The treatment effect of upper respiratory tract infection, pneumonia and mumps. However, the safety of Qingkailing injection has not been given by the analysis of the literature.
【学位授予单位】：北京中医药大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R286
[Abstract]:Qingkailing injection has two varieties of Qingkailing injection and injection Qingkailing (freeze-dried), which are mainly composed of cholic acid, porcine deoxycholic acid, water ox horn, baicalin, gardenia, honeysuckle, Radix Isatidis root, pearl mother. The effect is clearing heat and detoxifying, removing phlegm and dredging collaterals, opening the orifices, antivirus, antipyretic, anti-inflammatory, immune regulation, liver preservation and improvement. Qingkailing injection has a wide range of clinical applications, especially in cerebrovascular disease, upper respiratory tract infection, hepatitis, high fever and so on. The pharmacological basis, mechanism and clinical evaluation of Qingkailing injection have always been a hot topic in the academic field. In the study of network pharmacology, the mechanism of the action mechanism of Qingkailing injection was studied by using the multilevel biological network of "drug component - target disease", combined with gene functional annotation and KEGG pathway, and based on the evidence-based medical methods of Meta analysis and systematic evaluation, the methodological quality and phase of various clinical randomized controlled trials were evaluated scientifically. To provide more reliable evidence for the treatment of specific diseases by Qingkailing injection for clinical reference. Objective 1 to explore the pharmacological mechanism of Qingkailing injection and to reveal the pharmacological and functional characteristics of Qingkailing injection from the microcosmic point of view.2 system evaluation of Qingkailing injection for the treatment of acute upper respiratory infection, pneumonia, and epidemic parotid gland. The clinical efficacy and safety of inflammation. (I) network pharmacology uses public databases (such as TCMSP, PubChemCompound and TCMID) to collect the components and molecular information of Qingkailing injection, combined with the ADME properties and literature research of drug molecules, to predict and screen the active molecules, and to obtain their targets, gene and disease information, and use M Icrosoft Access 2010 constructs the database, extracts the data, uses the Cytoscape 3.4.0 software to construct the "drug component target disease" network map, carries out network topology analysis, determines the network key nodes or key modules, and then analyzes the main functions of the gene collection by GO function enrichment analysis and KEGG pathway enrichment analysis, and the multilevel and multi angle analysis. The effect mechanism of Qingkailing injection was discussed. (two) Meta analysis through the comprehensive retrieval of domestic and foreign literature database, including China know net, Wanfang, VP, SinMed, PubMed, Springer, Web of Science, Cochrane Central Register of Controlled, collect the clinical randomized controlled trial of Qingkailing injection for the treatment of specific diseases. The quality evaluation and data extraction were included in the standard RCTs, and Meta analysis was carried out for better homogeneity research. The result of forest map was presented. Meta regression, subgroup analysis, sensitivity analysis were used to investigate the heterogeneity, and sensitivity analysis was used to test the stability of the results. 1 database construction based on network pharmacology: the construction of "Qingkailing injection network pharmacology basic information database" contains 116 components, 1271 targets, 929 diseases, 3786 components, target, and disease correspondence.2 Qingkailing for the 8 drugs of Qingkailing injection network pharmacology. Analysis and Study on the mechanism of the action of injections: (1) the mechanism of the action of cholic acid - porcine deoxycholic acid: the main component of cholic acid, porcine deoxycholic acid has a better class property; the drug - drug - ingredient - target - disease network involves 6 targets and 8 diseases, and the key target is the MR and the liver X receptor (LXR a, LXR beta). Mainly related to brain injury, atherosclerosis, dyslipidemia and other diseases, GO enrichment mainly in the synthesis of triglycerides, cholesterol storage and regulation of biological processes, the KEGG pathway is mainly enriched in the insulin resistance pathway. (2) the "water cow angle pearl mother" mechanism: a total of 6 components, its overall drug resistance Well, the drug's "drug - component - target - disease" network involves 765 targets and 595 diseases, with prostaglandin endogenous peroxidase 2 (COX-2) and peroxisome proliferator activated receptor gamma (PPAR gamma) as the key target, with schizophrenia, Alzheimer's disease and inflammation as the highest degree of disease; GO enrichment is mainly in small molecular generations. KEGG pathway is mainly enriched in a variety of amino acid metabolic pathways. (3) the mechanism of "baicalin - Gardenia" is studied: a total of 20 components are screened, and their overall drug resistance is better; the drug "drug component target disease" network involves 198 targets and 369 diseases, with COX-2, PPARy, and 5- lipoxygenase. 5-LOX) and so on as the key target, the disease mainly involves tumor, diabetes, cardiovascular disease and so on. The enrichment of GO is mainly in the biological process of chemical stimulation response, cell proliferation regulation, cell apoptosis and programmed cell death regulation. The KEGG pathway is mainly enriched in many kinds of cancer pathways and hepatitis B pathway. (4) "honeysuckle isatis root" effect Mechanism study: a total of 92 components were screened, and their overall drug class was better; the drug "drug component target disease" network involved 665 targets and 609 diseases, with COX-2, heat shock protein 90 alpha (HSP86), prostaglandin synthase 1 (COX-1) and PPAR gamma as the key targets, and the disease mainly involved tumor, cardiovascular disease, diabetes, Alzheimer's disease, inflammation and so on; GO enrichment mainly in the cell surface receptor related signaling pathway, chemical stimulation response and other biological processes, the KEGG pathway is mainly enriched in the cAMP signal pathway, calcium signal pathway, various cancer pathways and hepatitis B pathway and other.3 Qingkailing injection mechanism of the overall study: a total of 116 COX-2, HSP86, COX-1 target value is the highest, mainly involving tumor, cardiovascular disease, diabetes, Alzheimer's disease, Alzheimer's disease, semen schizophrenia, inflammation and other diseases; GO enrichment mainly in chemical stimulation response, letter KEGG pathway is mainly enriched in cAMP signaling pathway, cGMP-PKG signaling pathway, multiple amino acid pathway, cancer pathway and hepatitis B pathway, and the GO enrichment of the 6 module corresponding genes is mainly in biological processes such as heart rate regulation, myocardial contraction regulation and other biological processes, KEGG pathway. The epinephrine signaling pathway and cGMP-PKG signaling pathway are mainly enriched in the cardiac myocytes; the GO enrichment of the 29 components corresponding to the permeability of the blood brain barrier is mainly in the biological process of cholesterol metabolism and cholesterol balance, and the KEGG pathway is mainly enriched in the PPAR signaling pathway, the synthesis pathway of various amino acids and the NiO Ding Chengyin pathway, etc. (two) clinical evaluation based on Meta analysis 1 Qingkailing Injection in the treatment of acute upper respiratory tract infection: 42 studies and 5905 cumulative patients; on the basis of single use or combined treatment of Western medicine, the total effectiveness of Qingkailing Injection in improving the clinical efficacy of acute upper respiratory infection is superior to Leigh Bhave Lin. Injection (RR=1.19,95%CI:1.16 ~ 1.22, P0.000 01), 12 studies reported 42 cases of adverse drug reactions / adverse events (ADRs/ADEs) in the experimental group, and 11 studies reported 34 cases of ADRs/ADEs.2 Qingkailing injection for pneumonia in the control group: 17 studies were included in 1702 cases, combined with antibiotics and symptomatic treatment. Qingkailing injection could improve the total effective efficiency of the treatment of pneumonia (RP= 1.23,95%CI:1.14 ~ 1.33, P0.000 01), 4 studies reported 27 cases of ADRs/ADEs in the experimental group and 64 cases of ADRs/ADEs.3 Qingkailing Injection in the control group for the treatment of epidemic parotitis: 7 studies, 580 cases of cumulative patients, and Qingkailing Injection combined with symptomatic treatment. The time of reducing the fever of epidemic parotitis was better than that of Leigh Bhave Lin injection combined with symptomatic treatment or only symptomatic treatment (MD =-1.16,95%CI:-1.36 to -0.96, P0.000 01); 3 studies did not occur ADRs/ADEs, 4 studies did not report ADRs/ADEs. study conclusion 1 the key node analysis of each drug pair of Qingkailing injection, gene GO function injection. The results of the analysis of the concentration and analysis of the KEGG pathway were focused, reflecting the differences in the efficacy of each drug and the interaction between the drugs and the mechanism of the action between each drug, reflecting the significance of the combination of medicine and compound medicine of traditional Chinese medicine (.2), the key of the Qingkailing injection may be affected by many components through the action on LXR, COX-2, HSP86 and PPAR gamma. Target, regulation of cholesterol metabolism and its internal balance, amino acid metabolism, cell proliferation, cell apoptosis and other biological processes involved in multiple signaling pathways, metabolic pathways and cancer pathways, and play a role in.3 injection in diseases such as tumors, cardiovascular diseases, diabetes, Alzheimer's disease, schizophrenia and inflammation. The drug is mainly used in cerebrovascular disease, and there are few reports on the treatment of cardiovascular diseases. However, this study found that many target targets, related pathways are closely related to myocardial infarction, ischemic heart disease and other cardiovascular diseases. It is worthwhile to further study the "drug composition target disease" and the overall prescription of.4 Qingkailing injection. The disease "network has a part of scale-free and small world characteristics, the module attribute is very low, the method of identifying key nodes is suitable for network analysis. The method of module analysis can choose.5 in clinical application according to the specific situation, compared with only conventional treatment of Western medicine or symptomatic treatment, combined with Qingkailing injection can improve the acute effect. The treatment effect of upper respiratory tract infection, pneumonia and mumps. However, the safety of Qingkailing injection has not been given by the analysis of the literature.
【学位授予单位】：北京中医药大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R286
【参考文献】
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