黄连防治鸭病毒性肠炎机制的网络药理学分析及动物试验验证

doi:10.11843/j.issn.0366-6964.2024.07.040

摘要/Abstract

摘要：

旨在探讨黄连防治鸭病毒性肠炎(duck viral enteritis, DVE)的作用机制，本研究首先应用中药系统药理学分析平台(Traditional Chinese Medicine System Pharmacology Analysis Platform, TCMSP)筛选黄连活性成分及作用靶点，GeneCards数据库分析DVE相关靶点，Venny和Cytoscape3.7.2软件绘制黄连与DVE交集靶点及构建“药物-成分-疾病-靶点”网络，利用STRING数据库建立蛋白相互作用网络(protein interaction network, PPI)，借助DAVID数据库进行靶点GO功能富集分析和KEGG通路富集分析，然后分正常对照组、病毒感染组和黄连防治组进行动物干预试验，采集组织样本进行病理组织学观察和相关细胞因子测定，结果表明：筛选出黄连14个活性成分和212个作用靶点，其中，与DVE交集的靶点25个，涉及RNA聚合酶Ⅱ启动子转录、序列特异性DNA结合转录因子活性、免疫应答、炎症反应和细胞凋亡等生物学过程，富集在Toll样受体信号通路、炎症性肠病、细胞因子-细胞因子受体相互作用、单纯疱疹病毒感染等信号通路，核心靶点是IL-6、IL-10和STAT1；病毒感染组鸭肝、脾和十二指肠发生不同程度的病理损伤，且这些组织中IL-6含量较正常对照组鸭显著提升(P≤0.05)，IL-10和STAT1含量显著降低(P≤0.05)，而黄连防治组鸭肝、脾和十二指肠组织病理损伤明显减轻，IL-6、IL-10和SYAT1含量趋于正常水平。由此可见，黄连能有效缓解鸭病毒性肠炎所致的鸭机体组织病理损伤，其作用机制涉及到多种炎症反应信号通路。

关键词: 黄连, 网络药理学, 鸭病毒性肠炎, 作用机制

Abstract:

To explore the mechanism of Coptidis Rhizoma treating duck viral enteritis (DVE), the active ingredients and targets of Coptidis Rhizoma were firstly screened by the Traditional Chinese Medicine System Pharmacology Analysis Platform (TCMSP), and the DVE related targets and their intersection targets with Coptidis Rhizoma were analyzed and drew using the GeneCards database and Venny and Cytoscape 3.7.2 software, which constructed a "drug component disease target" network. And the protein interaction network (PPI) were established by STRING databases and their GO function and KEGG pathway were analyzed with the DAVID database. Then, the results of network pharmacology were verified by animal experiments which narmol group, virus infection group and drug intervention group, and their tissue samples were collected for histopathological observation and related cytokine determination. The results showed that 14 active components and 212 action targets of Coptidis Rhizoma were selected, including 25 targets that intersect with DVE, involving biological processes such as RNA polymerase Ⅱ promoter transcription, sequence specific DNA binding transcription factor activity, immune response, inflammatory response, and cell apoptosis, enriched in signaling pathways such as Toll like receptor signaling, inflammatory bowel disease, cytokine-cytokine receptor interaction, and herpes simplex virus infection, the core targets are IL-6, IL-10, and STAT1. By animal experiments, there were the varting degrees of pathological damage in liver, spleen and duodenum in virus infection group ducks, and IL-6 content was significantly increased compared to the normal control group ducks (P≤0.05), while the IL-10 and STAT1 contents were significantly reduced (P≤0.05). However, the pathological damage was significantly reduced in drug intervention group ducks, the levels of IL-6, IL-10, and SYAT1 tended to normal levels. These results indicated that Coptidis can effectively alleviate the pathological damage of duck tissues caused by duck viral enteritis, and its mechanism may involves various inflammatory response signaling pathways.

Key words: Coptidis Rhizoma, network pharmacology, duck viral enteritis, mechanism

中图分类号:

S853.74

文安林, 杨芸芸, 罗永荣, 杨颖, 程振涛, 欧德渊, 文明. 黄连防治鸭病毒性肠炎机制的网络药理学分析及动物试验验证[J]. 畜牧兽医学报, 2024, 55(7): 3225-3233.

Anlin WEN, Yunyun YANG, Yongrong LUO, Ying YANG, Zhentao CHENG, Deyuan OU, Ming WEN. Network Pharmacologic Analysis and Experimential Verification on the Mechanism of Coptidis Rhizoma in Preventing Duck Viral Enteritis[J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(7): 3225-3233.

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序号 No.	活性成分编号 Mol ID	分子名称 Molecule name	口服生物利用度/% Oral bioavailability	类药性 Drug like properties
1	MOL001458	黄连碱 Coptisine	30.67	0.86
2	MOL000762	掌叶大黄二蒽酮 A Palmidin A	35.36	0.65
3	MOL002894	小蘖红碱 Berberrubine	35.74	0.73
4	MOL002904	小檗浸碱 Berlambine	36.68	0.82
5	MOL001454	小檗碱 Berberine	36.86	0.78
6	MOL002897	表小檗碱 Epiberberine	43.09	0.78
7	MOL013352	奥巴叩酮 Obacunone	43.29	0.77
8	MOL002668	甲基黄连碱 Worenine	45.83	0.87
9	MOL000098	槲皮素 Quercetin	46.43	0.28
10	MOL002903	R-氢化小檗碱(R)-Canadine	55.37	0.77
11	MOL000622	广玉兰内酯 Magnograndiolide	63.71	0.19
12	MOL000785	巴马汀 Palmatine	64.60	0.65
13	MOL008647	穆坪马兜铃酰胺 Moupinamide	86.71	0.26
14	MOL002907	黄麻甙 A Corchoroside A_qt	104.95	0.78

样本名称 Samples	检测指标 Index	组别 Group
样本名称 Samples	检测指标 Index	正常对照组 Normal control group	病毒感染组 Virus infection group	黄连干预组 Drug intervention group
肝 Liver	IL-6	15.13±0.28	26.62±0.12^**	17.22±0.76
	IL-10	38.63±0.20	34.38±0.25	39.54±0.26
	STAT1	237.88±2.96	185.43±4.19^*	204.85±6.27
脾 Spleen	IL-6	15.87±0.41	18.22±0.44^*	16.28±0.35
	IL-10	55.31±0.64	53.11±3.65	57.23±2.81
	STAT1	225.17± 1.27	176.86±7.86^*	217.52±4.82
十二指肠 Duodenum	IL-6	3.92±0.15	10.91±0.12^**	4.79±0.50
	IL-10	45.48±0.06	43.94±0.50	47.44±0.94
	STAT1	176.02± 5.50	146.86±2.14^*	169.68±4.21

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