| 林军,苏林红,叶小丹,等.五苓散治疗非酒精性脂肪性肝病的网络药理学研究和实验验证[J].浙江中医药大学学报,2020,44(11):1054-1060, 1070. |
| 五苓散治疗非酒精性脂肪性肝病的网络药理学研究和实验验证 |
| Network Pharmacology Research and Experimental Validation of Wuling San in Treating Non-alcoholic Fatty Liver Disease |
| DOI：10.16466/j.issn1005-5509.2020.11.005 |
| 中文关键词: 网络药理学 五苓散 非酒精性脂肪性肝病 作用机制 动物实验 肿瘤坏死因子-α 白细胞介素-17 p53 |
| 英文关键词: network pharmacology Wuling San non-alcoholic fatty liver disease mechanism of action animal experiment tumor necrosis factor-α interleukin-17 p53 |
| 基金项目:温州市科技局基础性医疗卫生科技项目(2018Y0663、Y20190720)；北京医卫健康公益基金会医学科学研究基金资助项目(YWJKJJHKYJJ-Q21J03) |
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| 中文摘要: |
| [目的]探讨五苓散治疗非酒精性脂肪性肝病(non-alcoholic fatty liver disease，NAFLD)的作用机制。[方法]利用中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology database and analysis platform，TCMSP)对五苓散中有效成分进行筛选及靶点预测，检索GeneCards、在线人类孟德尔遗传(online mendelian inheritance in man，OMIM)数据库筛选NAFLD疾病靶点，利用韦恩图在线平台筛选五苓散-NAFLD核心靶点，使用Cytoscape 3.7.1建立化合物-疾病-靶点调控网络，基于DAVID数据库对核心靶点进行基因本体(gene ontology，GO)功能富集分析和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes，KEGG)通路富集分析。建立NAFLD大鼠模型，五苓散干预28d后检测大鼠血清总胆固醇(total cholesterol，TC)、甘油三酯(triglyceride，TG)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol，LDL-C)水平，采用双抗体夹心酶联免疫吸附法检测大鼠肝组织肿瘤坏死因子-α(tumor necrosis factor-α，TNF-α)、p53蛋白、白细胞介素-17(interleukin-17，IL-17)表达水平，行苏木精-伊红(hematoxylin-eosin，HE)染色以观察肝组织病理学变化。[结果]基于TCMSP得到五苓散的27个有效成分和62个潜在靶点，经筛选获得与NAFLD疾病发生、发展相关的靶点1 732个，构建韦恩图得到五苓散治疗NAFLD的核心靶点27个，GO功能富集分析主要包括脂质反应、乙醇脱氢酶活性等功能途径；KEGG通路富集分析主要包括TNF信号通路、p53信号通路、IL-17信号通路等通路途径。动物实验结果显示，五苓散可显著降低NAFLD模型大鼠血清TC、TG、LDL-C水平，亦可显著降低肝组织TNF-α、p53、IL-17表达水平，同时肝组织病理变化显著改善。[结论]五苓散治疗NAFLD具有多成分、多靶点、多通路整体调节的作用特点，经实验证实五苓散能够改善NAFLD模型大鼠血清TC、TG、LDL-C水平，其作用可能与调控肝组织TNF-α、p53、IL-17表达有关。 |
| 英文摘要: |
| [Objective]To explore the mechanism of Wuling San(WLS) in treating non-alcoholic fatty liver disease(NAFLD) based on network pharmacology. [Methods]Use traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP) to screen effective components and targets of WLS， searching GeneCards， online mendelian inheritance in man(OMIM) to screen targets of NAFLD， constructing Venn online platform to get targets of WLS-NAFLD， use Cytoscape 3.7.1 to build component-disease-target network， analyzing gene ontology(GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment by DAVID database. After NAFLD model rats were established， they were administered with WLS for 28 days. The levels of serum total cholesterol(TC)， triglyceride(TG)， low density lipoprotein cholesterol(LDL-C) were measured. Enzyme linked immunosorbent assay was used to measure the levels of tumor necrosis factor-α(TNF-α)， p53， interleukin-17(IL-17) in liver tissue. hemaloxylin-eosin(HE) staining was performed to observe the pathological changes of liver tissue.[Results]Twenty-seven effective components and 62 potential targets of WLS were obtained based on TCMSP， 1 732 targets related to the occurrence and development of NAFLD were obtained， and 27 common targets of WLS-NAFLD were obtained. GO function enrichment analysis included response to lipid， alcohol dehydrogenase activity. KEGG pathway enrichment analysis included TNF signaling pathway， p53 signaling pathway，IL-17 signaling pathway. Animal experiment showed that WLS could significantly reduce the levels of serum TC， TG， LDL-C and the expression levels of TNF-α， p53 and IL-17 in liver tissue of NAFLD model rats. The pathological and morphological changes of the liver were improved.[Conclusion]WLS has the characteristics of multi-component， multi-target and multi-channel regulation in treating NAFLD. It is proved by experiments that WLS can improve the levels of serum TC， TG， LDL-C of NAFLD model rats， which may play a role by regulating the expression of TNF-α， p53 and IL-17 in liver tissue. |
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