Objective: To investigate the main components and potential mechanism of Shuxuening Injection(SXNI) in the treatment of myocardial ischemia-reperfusion injury(MIRI) through network pharmacology and in vivo research. M...Objective: To investigate the main components and potential mechanism of Shuxuening Injection(SXNI) in the treatment of myocardial ischemia-reperfusion injury(MIRI) through network pharmacology and in vivo research. Methods: The Traditional Chinese Medicine Systems Pharmacology(TCMSP) and Pharm Mapper databases were used to extract and evaluate the effective components of Ginkgo biloba leaves, the main component of SXNI. The Online Mendelian Inheritance in Man(OMIM) and Gene Cards databases were searched for disease targets and obtain the drug target and disease target intersections. The active ingredient-target network was built using Cytoscape 3.9.1 software. The STRING database, Metascape online platform, and R language were used to obtain the key targets and signaling pathways of the anti-MIRI effects of SXNI. In order to verify the therapeutic effect of different concentrations of SXNI on MIRI in rats, 60 rats were first divided into 5 groups according to random number table method: the sham operation group, the model group, SXNI low-dose(3.68 mg/kg), medium-dose(7.35 mg/kg), and high-dose(14.7 mg/kg) groups, with 12 rats in each group. Then, another 60 rats were randomly divided into 5 groups: the sham operation group, the model group, SXNI group(14.7 mg/kg), SXNI+LY294002 group,and LY294002 group, with 12 rats in each group. The drug was then administered intraperitoneally at body weight for 14 days. The main biological processes were validated using in vivo testing. Evans blue/triphenyltetrazolium chloride(TTC) double staining, hematoxylin-eosin(HE) staining, terminal deoxynucleotidyl transferase d UTP nick end labeling(TUNEL) assay, enzyme-linked immunosorbent assay(ELISA), and Western blot analysis were used to investigate the efficacy and mechanism of SXNI in MIRI rats. Results: Eleven core targets and 30 Kyoto Encyclopedia of Genes and Genomes(KEGG) pathways were selected. Among these, the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT) pathway was closely related to SXNI treatment of MIRI. In vivo experiments showed that SXNI reduced the myocardial infarction area in the model group, improved rat heart pathological damage, and reduced the cardiomyocyte apoptosis rate(all P<0.01). After SXNI treatment, the p-PI3K/PI3K and p-AKT/AKT ratios as well as B-cell lymphoma-2(Bcl-2) protein expression in cardiomyocytes were increased, while the Bax and cleaved caspase 3 protein expression levels were decreased(all P<0.05). LY294002 partially reversed the protective effect of SXNI on MIRI. Conclusion: SXNI protects against MIRI by activating the PI3K/AKT signaling pathway.展开更多
系统评价不同中成药联合常规西医治疗射血分数保留的心力衰竭的疗效及安全性,并进行用药排序。全面检索中国知网(CNKI)、万方(Wanfang)、维普(VIP)、中国生物医学文献服务系统(SinoMed)、PubMed、EMbase、Web of Science、Cochrane Libr...系统评价不同中成药联合常规西医治疗射血分数保留的心力衰竭的疗效及安全性,并进行用药排序。全面检索中国知网(CNKI)、万方(Wanfang)、维普(VIP)、中国生物医学文献服务系统(SinoMed)、PubMed、EMbase、Web of Science、Cochrane Library等建库至2022年10月9日涉及中成药治疗射血分数保留的心力衰竭的随机对照试验(randomized controlled trial,RCT),对纳入RCT使用R软件gemtc及rjags包进行网状Meta分析。共纳入74篇RCTs,7192例患者,涉及11种不同中成药(参附注射液、参麦注射液、芪苈强心胶囊、麝香保心丸、血脂康胶囊、丹参多酚酸盐注射液、丹参酮ⅡA磺酸钠注射液、心脉隆注射液、养心氏片、芪参益气滴丸、益心舒胶囊)。网状Meta分析疗效评价结果显示,①提高临床有效率方面,注射剂优选心脉隆注射液+常规西医,口服药选用麝香保心丸+常规西医、芪参益气滴丸+常规西医、芪苈强心胶囊+常规西医;②改善二尖瓣舒张早期血流峰值流速与舒张晚期血流峰值流速的比值(E/A)方面,注射剂选用参麦注射液+丹参多酚酸盐注射液+常规西医、参麦注射液+常规西医、参附注射液+常规西医,口服药优选益心舒胶囊+常规西医;③改善二尖瓣口舒张早期血流峰值速度与二尖瓣环舒张早期运动速度的比值(E/e′)方面,注射剂优选参附注射液+常规西医,口服药选用芪苈强心胶囊+常规西医、芪参益气滴丸+常规西医;④提高6 min步行试验(6MWT)方面,注射剂选用参麦注射液+常规西医、心脉隆注射液+常规西医,口服药选用芪参益气滴丸+常规西医、芪苈强心胶囊+常规西医;⑤降低N末端B型利钠肽前体(NT-proBNP)水平方面,口服药优选芪苈强心胶囊+常规西医;⑥降低B型利钠肽(BNP)方面,注射液优选心脉隆注射液+常规西医,口服药优选芪苈强心胶囊+常规西医。中成药联合常规西医不良反应与单纯常规西医相比,差异无统计学意义。结果表明,中成药联合常规西医治疗射血分数保留的心力衰竭在减轻临床症状、改善心功能、提高运动耐量方面优于单纯常规西医,且具有良好的用药安全性。但现有证据受限于纳入文献的质量与数量,以上结论需更多前瞻性RCT进一步验证。展开更多
基金Supported by the National Natural Science Foundation of China (No.82274316)the Special Project for the Scientific Research of Traditional Chinese Medicine in Henan Province (No.2022ZYZD01)。
文摘Objective: To investigate the main components and potential mechanism of Shuxuening Injection(SXNI) in the treatment of myocardial ischemia-reperfusion injury(MIRI) through network pharmacology and in vivo research. Methods: The Traditional Chinese Medicine Systems Pharmacology(TCMSP) and Pharm Mapper databases were used to extract and evaluate the effective components of Ginkgo biloba leaves, the main component of SXNI. The Online Mendelian Inheritance in Man(OMIM) and Gene Cards databases were searched for disease targets and obtain the drug target and disease target intersections. The active ingredient-target network was built using Cytoscape 3.9.1 software. The STRING database, Metascape online platform, and R language were used to obtain the key targets and signaling pathways of the anti-MIRI effects of SXNI. In order to verify the therapeutic effect of different concentrations of SXNI on MIRI in rats, 60 rats were first divided into 5 groups according to random number table method: the sham operation group, the model group, SXNI low-dose(3.68 mg/kg), medium-dose(7.35 mg/kg), and high-dose(14.7 mg/kg) groups, with 12 rats in each group. Then, another 60 rats were randomly divided into 5 groups: the sham operation group, the model group, SXNI group(14.7 mg/kg), SXNI+LY294002 group,and LY294002 group, with 12 rats in each group. The drug was then administered intraperitoneally at body weight for 14 days. The main biological processes were validated using in vivo testing. Evans blue/triphenyltetrazolium chloride(TTC) double staining, hematoxylin-eosin(HE) staining, terminal deoxynucleotidyl transferase d UTP nick end labeling(TUNEL) assay, enzyme-linked immunosorbent assay(ELISA), and Western blot analysis were used to investigate the efficacy and mechanism of SXNI in MIRI rats. Results: Eleven core targets and 30 Kyoto Encyclopedia of Genes and Genomes(KEGG) pathways were selected. Among these, the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT) pathway was closely related to SXNI treatment of MIRI. In vivo experiments showed that SXNI reduced the myocardial infarction area in the model group, improved rat heart pathological damage, and reduced the cardiomyocyte apoptosis rate(all P<0.01). After SXNI treatment, the p-PI3K/PI3K and p-AKT/AKT ratios as well as B-cell lymphoma-2(Bcl-2) protein expression in cardiomyocytes were increased, while the Bax and cleaved caspase 3 protein expression levels were decreased(all P<0.05). LY294002 partially reversed the protective effect of SXNI on MIRI. Conclusion: SXNI protects against MIRI by activating the PI3K/AKT signaling pathway.
