基于代谢组学和网络药理学探讨细辛-干姜药对对COPD大鼠肺、肝脂质代谢的影响  

Effect of Asari Radix et Rhizoma-Zingiberis Rhizoma Herb Pair on Lung and Liver Lipid Metabolism in Rats with COPD Based on Metabolomics and Network Pharmacology

作　　者：黄萍 周祯祥[1] 李德顺[1] 黄芳[1] 李晶晶[1] 段白露[1] 韩林涛[1] 赵永 汪琼[1] HUANG Ping;ZHOU Zhenxiang;LI Deshun;HUANG Fang;LI Jingjing;DUAN Bailu;HAN Lintao;ZHAO Yong;WANG Qiong(Hubei University of Chinese Medicine,Wuhan 430000,China;Central Theater General Hospital of PLA,Wuhan 430000,China)

机构地区：[1]湖北中医药大学,武汉430000 [2]中国人民解放军中部战区总医院,武汉430000

出　　处：《中国实验方剂学杂志》2022年第18期152-160,共9页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(81903815);湖北省教育厅科技项目(B2019100)。

摘　　要：目的探讨细辛-干姜药对(XGHP)对慢性阻塞性肺疾病(COPD)大鼠肺、肝脏脂质代谢的影响。方法40只SD雄性大鼠,分为正常组(10只)和模型组(30只),采用香烟烟雾+气管注射脂多糖(LPS)+冷刺激复制COPD寒饮伏肺证模型,造模成功后分COPD组、XGHP组(5.4 g·kg^(-1)·d^(-1)),氨茶碱组(0.5 g·kg^(-1)·d^(-1)),各10只,治疗结束后,检测各组大鼠血清中甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)水平。采用气相色谱-质谱联用技术(GC-MS)检测各组大鼠肺、肝组织的差异代谢物,网络药理学预测差异代谢物的靶点,取两脏交集靶点,作基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析。分子对接计算XGHP中的主要成分与网络药理学中相关靶点的结合能力。运用实时荧光定量聚合酶链式反应(Real-time PCR)和蛋白免疫印迹法(Western blot)检测肺、肝组织过氧化物酶体增殖物激活受体α(PPARα)、脂肪酸结合蛋白4(FABP4)mRNA和蛋白表达水平。结果XGHP明显升高COPD大鼠血清中的TG、TC、LDL-C的水平(P<0.05),明显降低HDL-C的水平(P<0.05)。GC-MS分析,COPD组和XGHP组中肺脏差异代谢物有8个,肝脏差异代谢物17个。网络药理学预测两脏差异代谢物的共同靶点59个,主要富集在PPAR信号通路。分子对接结果显示,XGHP中的主要成分与PPARα、FABP4均结合良好。Real-time PCR和Western blot结果显示XGHP能有效上调COPD大鼠肺、肝组织PPARα、FABP4 mRNA和蛋白表达水平(P<0.05)。结论XGHP能改善COPD大鼠血脂水平,可能与增加PPAR信号通路上PPARα、FABP4 mRNA和蛋白的表达水平相关,从而调节肺脏和肝脏脂质代谢。Objective To investigate the effects of Asari Radix et Rhizoma-Zingiberis Rhizoma herb pair(XGHP)on lung and liver lipid metabolism in rats with chronic obstructive pulmonary disease(COPD).Method Forty SD male rats were divided into a normal group(10 rats)and a model group(30 rats).The method of cigarette smoke+tracheal injection of lipopolysaccharide(LPS)+cold stimulation was used to replicate COPD model with the syndrome of cold phlegm obstruction in lung.A COPD group,a XGHP group(5.4 g·kg^(-1)·d^(-1)),and an aminophylline group(0.5 g·kg^(-1)·d^(-1))were established after successfully inducing the model,with 10 rats in each group.After treatment,the serum triglyceride(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C)levels of rats in each group were measured.Gas chromatography-mass spectrometer(GC-MS)was used to detect the differential metabolites in the lung and liver tissues of rats in each group,and the relevant targets of the differential metabolites were predicted by network pharmacology.Molecular docking was used to verify the binding ability of key components in XGHP to the relevant targets in network pharmacology.The mRNA and protein expression levels of peroxisome proliferator-activated receptorα(PPARα)and fatty acid binding protein 4(FABP4)in lung and liver tissues of rats in each group were detected by real-time polymerase chain reaction(PCR)and Western blot.Result XGHP significantly increased the levels of TG,TC,and LDL-C in serum(P<0.05),and decreased the level of HDL-C(P<0.05)in rats with COPD.GC-MS results showed that there were 8 lung differential metabolites and 17 liver differential metabolites in the COPD group and XGHP group.Network pharmacology predicted 59 common targets for the two differential metabolites,mainly enriched in the PPAR signaling pathway.Molecular docking results showed that the main components in XGHP were well combined with both PPARαand FABP4.Real-time PCR showed that XGHP effectively up-regulated t

关 键 词：细辛-干姜药对 慢性阻塞性肺疾病(COPD) 脂质代谢 过氧化物酶体增殖物激活受体(PPAR)信号通路 代谢组学 

分 类 号：R285[医药卫生—中药学] R289[医药卫生—中医学] R22R2-031R33