穿心莲用于妊娠胆汁淤积症的作用机制  

The mechanism of Andrographis paniculata for intrahepatic cholestasis of pregnancy

作　　者：薛莲芳[1] 刘慧[1] 丘穗珊 朱勤爱[2] 王玉平 罗惠娟[3] XUE Lianfang;LIU Hui;QIU Suishan;ZHU Qinai;WANG Yuping;LUO Huijuan(Department of Pharmacy,the First Affiliated Hospital of Jinan University,Guangzhou 510630,China;Clinical Medical Laboratory Center,the First Affiliated Hospital of Jinan University,Guangzhou 510630,China;Maternity Department,the First Affiliated Hospital of Jinan University,Guangzhou 510630,China)

机构地区：[1]暨南大学附属第一医院药学部,广东广州510630 [2]暨南大学附属第一医院临床医学检验中心,广东广州510630 [3]暨南大学附属第一医院产科,广东广州510630

出　　处：《暨南大学学报（自然科学与医学版）》2021年第3期284-292,338,共10页Journal of Jinan University(Natural Science & Medicine Edition)

基　　金：广东省中医药局资助项目(20191089)。

摘　　要：目的:采用网络药理学方法全面系统筛选穿心莲治疗妊娠胆汁淤积症的作用靶点及相关信号通路,并通过动物实验进一步明确其作用机制.方法:利用中药系统药理学数据库TCMSP筛选穿心莲的有效化学成分,整合多种系统生物数据库构建“活性成分-疾病-靶点”网络关系,对共有蛋白互作PPI网络基因进行功能富集分析,对有效成分进行动物实验验证.结果:穿心莲包含24个活性成分,包括穿心莲黄酮、穿心莲内酯、汉黄芩素和穿心莲黄酮甙F、14-去氧-12-甲氧基穿心莲内酯等,这些活性成分与妊娠胆汁淤积相关的30个潜在靶点蛋白发生相互作用,其中包含JUN,ESR1,IL6,NOS2,DPP4,CCL2,NR3C2,KDR,CKD2,CCNA2,CDKN1A,PPARG,RELA和CASP9等.实验结果显示,血液生化指标显示造模成功,穿心莲内酯高、中剂量治疗组对ICP模型孕鼠各项生化指标均有明显改善作用(P<0.05),低剂量组无明显改善.高、中剂量组可显著提高胎鼠成活数与胎鼠平均质量(P<0.05),低剂量组与模型组比较未见显著差异.结论:穿心莲内酯可以改善孕鼠ICP引起的血液生化指标异常,同时提高胎鼠存活率.Objective:To explore the targets and related signaling pathways of Andrographis paniculata for Intrahepatic cholestasis of pregnancy using network pharmacology,and animal experiments are applied to further clarify its mechanism of action.Methods:TCMSP database was used to screen the active chemical components of Andrographis paniculata,and varieties of systematic biological databases were integrated to construct the“active component-disease-target”network relationship,and the common PPI network genes were functionally enriched.The active ingredients were verified by animal experiments.Results:Andrographis paniculata contains 24 active ingredients the active ingredient related to Intrahepatic cholestasis of pregnancy 30 potential target proteins interact,and which contains JUN,ESR1,IL6,NOS2,DPP4,CCL2,NR3C2,KDR,CKD2,CCNA2,CDKN1A,PPARG,RELA and CASP9,etc.The experimental results showed that the blood biochemical indexes(BBI)showed that the ICP model was successful established,and the BBI levels in the high and medium dose group had significant decreased when compared with the model group(P<0.05),while there were none difference of BBI were found between the low dose group and the model group.The number of fetal in the high dose group was significantly higher than that in the other groups,and there was no significant difference between the low-dose group and the model group.Conclusion:Andrographolide can normalize the BBI in ICP rats,and has a certain restorative effect on fetal rats number and qulity.

关 键 词：穿心莲 穿心莲内酯 网络药理学 肝内胆汁淤积症 动物实验 

分 类 号：R714.255[医药卫生—妇产科学]