摘要
目的:研究齐墩果酸对B淋巴细胞损伤的保护作用并基于网络药理学方法阐明其作用机制。方法:在实验第1~5天每天给昆明小鼠腹腔注射环磷酰胺80 mg/kg以建立免疫抑制动物模型。从造模第6天开始每天给予25 mg/kg齐墩果酸处理,连续28 d作为干预组,同时设置模型组和空白组作为对照。采用流式细胞术检测各组小鼠的骨髓B淋巴细胞亚群百分率。为探索齐墩果酸的作用机制,进一步使用PubChem数据库获得齐墩果酸的化学结构,用SwissTargetPrediction数据库预测齐墩果酸的药物靶点,通过String平台对潜在的药物靶点进行蛋白质相互作用网络分析、基因本体(GO)生物过程富集分析和京都基因与基因组百科全书(KEGG)信号通路富集分析。结果:在给药28 d后,模型组的成熟B细胞亚群(IgD与B220双阳性细胞)百分率为(2.585±0.248)%,明显低于空白组的(8.235±0.361)%,差异具有统计学意义(P<0.01),说明免疫抑制动物模型成功建立;而齐墩果酸干预组的成熟B细胞亚群百分率为(3.395±0.445)%,明显高于模型组,差异具有统计学意义(P<0.01)。通过SwissTargetPrediction数据库筛选到PTPN1、CD81等齐墩果酸的潜在药物靶点。经String平台分析和Cytoscape绘图计算后,连通性排名前5的节点蛋白有PPARG、PTGS2、PPARA、MAPK3和HMGCR。通过GO生物过程富集分析及KEGG信号通路分析得出,齐墩果酸的药理作用富集于脂质储存的负调控等生物过程及B细胞受体(BCR)信号通路。结论:齐墩果酸能够增加骨髓成熟B细胞亚群的百分率,其机制可能是通过影响BCR信号通路在B淋巴细胞的发育过程中发挥作用。
OBJECTIVE:This study evaluated the protective effect of oleanolic acid on cyclophosphamide-induced B lymphocyte injury in mice.METHODS:Kunming mice were given cyclophosphamide(80 mg/kg)per day to establish an immunosuppressive animal model.After modeling,oleanolic acid(25 mg/kg)was given per day for 28 days as the interventional group.At the same time,the model group and the blank group were set as controls.The percentage of bone marrow B lymphocyte subsets in each group was detected by flow cytometry.The chemical structure of oleanolic acid was obtained by PubChem database,and the drug target of oleanolic acid was predicted by the Swiss Target Prediction database.Analyses viathe protein interaction network,GO biological process enrichment and KEGG signal pathway enrichment of potential drug targets were carried out by the STRING platform.RESULTS:After administration of cyclophosphamide,the percentage of mature B cell subsets(IgD and B220 double positive cells)in the model group(2.585%±0.248%)was significantly lower than that in the blank group(8.235%±0.361%),while the percentage in the oleanolic acid interventional group(3.395%±0.445%)was significantly higher than that in the model group(P<0.01).Potential drug targets of oleanolic acid such as PTPN1 and CD81 were screened by the Swiss Target Prediction database.After SRTING platform analysis and Cytoscape remapping calculation,the top 5 node proteins in connectivity were PPARG,PTGS2,PPARA,MAPK3 and HMGCR.From the GO biological process enrichment and KEGG signaling pathway analyses,the pharmacological effects of oleanolic acid were enriched in biological processes such as negative regulation of lipid storage and B cell receptor signaling pathway.CONCLUSION:Oleanolic acid administration to mice increased the percentage of mature B cell subsets in bone marrow and enhanced the development of B lymphocytes by affecting the BCR signaling pathway.
作者
代雨鑫
梁立春
彭琳茜
孟凡奇
韩献锋
张玥
杨玉
商宇
DAI Yuxin;LIANG Lichun;PENG Linqian;MENG Fanqi;HAN Xianfeng;ZHANG Yue;YANG Yu;SHANG Yu(Key Laboratory of Microecology-Immune Regulatory Network and Related Diseases School of Basic Medicine,Jiamusi University,Jiamusi 154007;School of Clinical Medicine,Jiamusi University,Jiamusi 154003,Heilongjiang,China)
出处
《癌变．畸变．突变》
CAS
2024年第1期48-52,共5页
Carcinogenesis,Teratogenesis & Mutagenesis
基金
黑龙江省大学生创新创业项目(202010222016,202010222017)
黑龙江省卫健委科研课题(20210202040066)
佳木斯大学青年创新人才培养项目(JMSUQP2020012)。
关键词
齐墩果酸
B淋巴细胞发育
网络药理学
信号通路
oleanolic acid
B cell development
network pharmacology
signaling pathway
