安宫牛黄丸抗心力衰竭作用的跨尺度多向药理学研究  

Effects of Angong Niuhuang Pills against heart failure based on cross-scale polypharmacological study

作　　者：史雪敬 金强 赵誉 许麦成 张寒 盛洪达 王毅[3] 赵筱萍[1,4] SHI Xue-jing;JIN Qiang;ZHAO Yu;XU Mai-cheng;ZHANG Han;SHENG Hong-da;WANG Yi;ZHAO Xiao-ping(School of Basic Medical Sciences,Zhejiang Chinese Mediail University,Hangzhou 310053,China;Hangzhou Hu Qing Yu Tang Pharmaieutiral Co.,Ijd.,Hangzhou 311100,China;College of Pharmaceuticdl Sciences,Zhejiang University,Hangzhou 310058,China;Academy of Chinese Medical Science,Zhejiang Chinese Medical University,Hangzhou 310053,China)

机构地区：[1]浙江中医药大学基础医学院,浙江杭州310053 [2]杭州胡庆余堂药业有限公司,浙江杭州311100 [3]浙江大学药学院,浙江杭州310058 [4]浙江中医药大学中医药科学院,浙江杭州310053

出　　处：《中国中药杂志》2022年第7期1888-1896,共9页China Journal of Chinese Materia Medica

基　　金：国家重点研发计划项目(2018YFC1704502)。

摘　　要：安宫牛黄丸具有清热解毒、豁痰开窍的功效,临床常用于治疗热入心包所致的高热惊厥等疾病,但其对心力衰竭的治疗作用尚未得到关注。该研究采用超高效液相色谱-串联飞行时间质谱(UPLC-Q-TOF-MS)联用技术,辨析安宫牛黄丸调控的差异代谢物,结合药效学数据与代谢网络的融合分析,研究安宫牛黄丸抗心力衰竭的潜在作用机制。建立异丙肾上腺素诱导的小鼠心力衰竭模型,给予安宫牛黄丸灌胃1周,然后进行超声心动图检测评价药效,收集血清样本进行代谢组学分析。通过偏最小二乘判别分析(PLS-DA)筛选出安宫牛黄丸抗心力衰竭的8个显著性差异代谢物,后导入MetaboAnalyst数据库进行相关代谢通路分析;对安宫牛黄丸主要化合物的潜在靶点进行筛选,并富集关键代谢通路;将安宫牛黄丸给药后部分代谢物相对含量回调指数与整体药效数据进行跨尺度融合分析,进一步进行“化合物-反应-酶-基因”网络分析。综合分析,推测安宫牛黄丸抗心力衰竭作用可能主要与花生四烯酸、氨基酸、甘油磷脂及亚油酸代谢相关。该文所建立的跨尺度多向药理作用的辨析方法,为运用现代科学技术解读安宫牛黄丸抗心力衰竭作用的科学内涵提供了新途径。Angong Niuhuang Pills(AGNHP) are effective in clearing heat, removing the toxin, and eliminating phlegm for resuscitation. Clinically, it is widely used to treat various diseases such as febrile convulsion due to heat attacking pericardium, but its therapeutic effects on heart failure(HF) have not been well recognized. In this study, the profiles of differential metabolites regulated by AGNHP were identified by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS). The underlying mechanism of AGNHP against HF was illustrated based on the integrated analysis of pharmacological data and metabolic molecular network. The HF model was induced by isoproterenol in mice. After oral administration of AGNHP for one week, cardiac functions in HF mice were evaluated by echocardiography, and serum samples of mice were collected for metabolomics analysis. Eight differential metabolites of AGNHP against HF were screened out through partial least square discriminant analysis(PLS-DA) and input into MetaboAnalyst for the analysis of metabolic pathways. Moreover, the critical metabolic pathways regulated by AGNHP were enriched according to the potential targets of major compounds in AGNHP. After AGNHP treatment, the recovered index of relative content of some metabolites underwent cross-scale fusion analysis with therapeutic efficacy data, followed by "compound-reaction-enzyme-gene" network analysis. It is inferred that the anti-HF effects of AGNHP may be attributed to the metabolism of arachidonic acid, amino acid, glycerophospholipid, and linoleic acid. The cross-scale polypharmacological analysis method developed in this study provides a new method to interpret scientific principles of AGNHP against HF with modern technologies.

关 键 词：安宫牛黄丸 心力衰竭 多向药理学 差异代谢物 通路分析 跨尺度融合分析 

分 类 号：R285.5[医药卫生—中药学]