首页|当归散改善克罗米芬诱导子宫内膜血管发育不良的生物机制探讨

当归散改善克罗米芬诱导子宫内膜血管发育不良的生物机制探讨

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[目的]基于网络药理学和动物实验,探究当归散及其拆方对克罗米芬诱导子宫内膜血管发育不良的作用效果.[方法]通过中药系统药理学数据库与分析平台(TCMSP)、Swiss Target Predicition数据库获取当归散成分及靶点,利用人类基因数据库(Gene Cards)、人类孟德尔遗传(OMIM)数据库检索克罗米芬导致子宫内膜血管发育不良相关的疾病靶点,两者取交集后,构建"中药-成分-靶点"网络图、蛋白互作(PPI)网络,进行GO功能、京都基因和基因组百科全书(KEGG)通路富集分析.模型组和各给药组大鼠于动情期后第 1 天起,连续 5d灌胃克罗米芬混悬液造模;各给药组每日分别予阳性对照药物阿司匹林、当归散、川芎-当归-芍药、黄芩-白术供试液,连续 8d.免疫组化法测定大鼠子宫内膜微血管密度、血管内皮生长因子(VEGFA)及其受体血管内皮生长因子受体 1(FLT1)、血管内皮细胞生长因子受体 2(KDR)、血管生成素(Ang)1、Ang2 及其受体内皮细胞TEK酪氨酸激酶(Tie2)的表达.[结果]网络药理学得到VEGFA、表皮生长因子受体(EGFR)、成纤维细胞生长因子 2(FGF2)、KDR、原癌基因酪氨酸蛋白激酶(SRC)、FLT1 等当归散核心作用靶点 24 个,GO富集分析涉及生物过程 1 524 个条目、细胞组分 36 个条目和分子功能94 个条目,KEGG通路富集得到磷脂酰肌醇-3-激酶-蛋白激酶(PI3K-Akt)信号通路、Rap1 信号通路、松弛素信号通路等 118 条通路.与正常组相比,模型组子宫内膜微血管密度显著降低,VEGFA及其受体FLT1、KDR,Ang1、Ang2 及其受体Tie2 表达水平显著下降(P<0.01).与模型组相比,各药物组微血管密度提高,KDR、FLT1、Ang1、Ang2、Tie2 表达升高(P<0.05 或P<0.01);除黄芩白术组,其余各用药组大鼠子宫内膜VEGFA的表达水平均显著升高(P<0.01).[结论]当归散及其拆方可以不同程度地改善克罗米芬造成的大鼠子宫内膜微血管密度下降,恢复VEGFA及其受体FLT1、KDR,Ang1、Ang2 及其受体Tie2 表达水平,提高子宫内膜容受性.
Biological mechanism of Danggui Powder in improving endometrial vascular dysplasia induced by clomiphene citrate
[Objective]To study the effect of Danggui Powder and its disassembled prescriptions on dysplasia endometrial vascular caused by clomiphene citrate,based on network pharmacology and experimental verification.[Methods]TCMSP and SwissTargetPredicition databases were used to obtain the active components and potential drug targets of Danggui Powder.GeneCards and OMIM databases were used to search the targets of dysplasia endometrial vascular caused by clomiphene citrate.The intersection of drugs and dysplasia endometrial vascular related targets was selected.The network of"Chinese medicine-core component-target"and the protein-protein interactions(PPI)network were conducted.The enrichment analysis of GO and KEGG were carried out.On the first day after estrus,the model group and each treatment group were given clomiphene suspension for 5 consecutive days.Meanwhile,the treatment groups were given aspirin,Danggui Powder,Chuanxiong-Danggui-Shaoyao,Huangqin-Baizhu solution for 8 consecutive days.The rat endometrial microvessel density,the expression of vascular endothelial growth factor VEGFA,FLT1,KDR,Ang1,Ang2 and Tie2 were determined by Immunohistochemistry.[Results]A total of 24 potential targets of Danggui Powder were obtained by network pharmacology,such as VEGFA,EGFR,FGF2,KDR,SRC,FLT1,etc.A total of 1524 items of biological processes,36 items of cellular components and 94 items of molecular functions were involved in the enrichment analysis of GO.And 118 pathways were involved in the enrichment analysis of KEGG,such as PI3K-Akt signaling pathway,Rap1 signaling pathway,Relaxin signaling pathway,etc.Compared with the normal group,the rat endometrial microvessel density,VEGFA,FLT1,KDR,Ang1,Ang2 and Tie2 in the model group significantly decreased(P<0.01).Compared with the model group,the rat endometrial microvessel density,KDR,FLT1,Ang1,Ang2 and Tie2 in each treatment group increased(P<0.05 or P<0.01).In addition to the Huangqin-Baizhu group,VEGFA in the other treatment groups significantly increased(P<0.01).[Conclusion]Danggui Powder and its disassembled prescription can reduce the damage of clomiphene citrate for endometrial to varying degrees,restore the expression of VEGFA,FLT1,KDR,Ang1,Ang2 and Tie2,and improve the endometrial receptivity.

Danggui Powderclomiphene citratevascular endothelial growth factor(VEGF)angiogeninendometrial angiogenesisnetwork pharmacology

张楚欣、程宇立、胡红林、胡瑞瑶、高琳

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北京中医药大学,北京 100029

杭州树兰医院中医科,杭州 310015

当归散 克罗米芬 血管内皮生长因子 血管生成素 子宫内膜血管发育 网络药理学

国家自然科学基金北京市自然科学基金

30801463J190016

2024

天津中医药
天津市中医药大学,天津中西医结合学会,天津中医药学会

天津中医药

CSTPCD
影响因子:0.998
ISSN:1672-1519
年,卷(期):2024.41(2)
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