摘要
目的基于网络药理学及实验验证探究清热利胆汤治疗胆汁瘀积性肝损伤的作用机制。方法采用网络药理学方法筛选清热利胆汤和胆汁瘀积性肝损伤相关的核心靶点,构建基于活性成分与疾病共同靶点的蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络,利用DAVID数据库对潜在作用靶点进行京都基因与基因组百科全书(Kyoto encyclopedia ofgenesandgenomes,KEGG)通路富集分析,通过分子对接方法验证活性成分与关键靶点的结合作用。采用胆管结扎方法建立胆汁瘀积性肝损伤大鼠模型,给予思美泰及清热利胆汤进行干预,考察各组大鼠血清中天冬氨酸转氨酶(aspartate aminotransferase,AST)、丙氨酸转氨酶(alanineaminotransferase,ALT)活性以及总胆红素(totalbilirubin,TBIL)、直接胆红素(direct bilirubin,DBIL)和总胆汁酸(total bile acid,TBA)水平;考察各组大鼠肝组织病理变化;考察各组大鼠肝脏组织蛋白激酶Cα(protein kinase Cα,PRKCA)、原癌基因丝氨酸/苏氨酸蛋白激酶1(protooncogene serine/threonine-protein kinase 1,RAF1)、双特异性丝裂原活化蛋白激酶1(dual specificity mitogen-activated protein kinase 1,MAP2K1)和丝裂原活化蛋白激酶1(mitogen-activated protein kinase 1,MAPK1)m RNA表达情况。结果网络药理学分析显示,清热利胆汤可能通过作用于PRKCA、RAF1、MAP2K1和MAPK1靶点,参与MAPK信号通路,从而治疗胆汁瘀积性肝损伤;原花青素B2与MAP2K1、槲皮素与MAPK1具有较好的结合能力。与模型组比较,清热利胆汤组大鼠血清中ALT活性和TBA水平显著降低(P<0.05),肝组织病理损伤得到改善;肝脏组织中PRKCA、MAP2K1和MAPK1 mRNA表达水平显著降低(P<0.05、0.01),RAF1 mRNA表达水平显著升高(P<0.01)。结论清热利胆汤能够通过调控PRKCA、RAF1、MAP2K1和MAPK1,从而治疗胆汁瘀积性肝损伤。
Objective To explore the mechanism of Qingre Lidan Decoction(清热利胆汤) on cholestatic liver injury based on network pharmacology and experimental verification. Methods Core targets related to Qingre Lidan Decoction and cholestatic liver injury were screened, and protein-protein interaction(PPI) network based on common target of active ingredients and disease was constructed by network pharmacology. DAVID database was used to perform Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis on potential targets, molecular docking methods was used to verify the binding effect of active ingredients with key targets. Bile duct ligation was used to establish a rat model of cholestatic liver injury, Simeite and Qingre Lidan Decoction were administered to intervene, levels of aspartate aminotransferase(AST), alanine aminotransferase(ALT), total bilirubin(TBIL), direct bilirubin(DBIL) and total bile acid(TBA) in serum of rats in each group were investigated;Pathological changes of liver tissues of rats in each group were investigated;m RNA expressions of protein kinase C α(PRKCA), protooncogene serine/threonine-protein kinase 1(RAF1), dual specificity mitogen-activated protein kinase 1(MAP2K1) and mitogen-activated protein kinase 1(MAPK1) in liver of rats were investigated. Results Network pharmacological analysis showed that Qingre Lidan Decoction participated in MAPK signaling pathway by acting on the targets of PRKCA, RAF1, MAP2K1 and MAPK1, thereby treating cholestatic liver injury;Procyanidin B2 and MAP2K1, quercetin and MAPK1 had a good binding ability. Compared with model group, levels of ALT and TBA in serum of rats in Qingre Lidan Decoction group were significantly reduced(P < 0.05), and pathological damage in liver tissue was improved;Expressions of PRKCA, MAP2K1 and MAPK1 m RNA in liver tissue were significantly reduced(P < 0.05, 0.01), RAF1 mRNA expression was significantly increased(P < 0.01). Conclusion Qingre Lidan Decoction can treat cholestatic liver injury by regulating PRKCA, RA
作者
黄彭
曲佳琳
段文倩
韦天夫
张洋
蔡明宸
张雪扬
张桂信
冷爱晶
HUANG Peng;QU Jia-lin;DUAN Wen-qian;WEI Tian-fu;ZHANG Yang;CAI Ming-chen;ZHANG Xue-yang;ZHANG Gui-xin;LENG Ai-jing(Clinical Laboratory of Integrative Medicine,First Affiliated Hospital of Dalian Medical University,Dalian 116011,China;Institute of Integrative Medicine,Dalian Medical University,Dalian 116044,China;Department of Respiratory and Critical Care Medicine,Suixian People’s Hospital of Henan Province,Shangqiu 476900,China;Department of Traditional Chinese Medicine,First Affiliated Hospital of Dalian Medical University,Dalian 116011,China;Department of Endocrinology,First Affiliated Hospital of Dalian Medical University,Dalian 116011,China;Department of General Surgery,First Affiliated Hospital of Dalian Medical University,Dalian 116011,China)
出处
《中草药》
CAS
CSCD
北大核心
2021年第15期4577-4586,共10页
Chinese Traditional and Herbal Drugs
基金
国家自然科学基金资助项目(81703675)
辽宁省自然资金指导计划项目(2019-ZD-0914,2019-ZD-0631)
辽宁省教育厅科学研究经费项目自然科学类(LZ2020015)。
