基于网络药理学和动物实验探讨养血荣筋丸治疗糖尿病微血管病变的作用  

The Effect of Yangxue Rongjin Pill(养血荣筋丸)on Diabetic Microangionopathy Based on Network Pharmacology And Animal Experiments

作　　者：靳冉 岳枫 裴海鸾 张晓笛 徐意 李晋生[2] JIN Ran;YUE Feng;PEI Hailuan;ZHANG Xiaodi;XU Yi;LI Jinsheng(Beijing Tongrentang Technologies Development Co.,Ltd.Pharmaceutical Factory,Beijing 100079,China;Institute of Scientific Research,Beijing Tongrentang Company Limited by Shares,Beijing 100079,China)

机构地区：[1]北京同仁堂科技发展股份有限公司制药厂,北京100079 [2]北京同仁堂股份有限公司科学研究所,北京100079

出　　处：《中医药导报》2025年第3期37-44,88,共9页Guiding Journal of Traditional Chinese Medicine and Pharmacy

摘　　要：目的:基于网络药理学和动物实验探讨养血荣筋丸治疗糖尿病微血管病变(DMA)的作用。方法:利用TCMSP、ETCM和PubChem数据库筛选养血荣筋丸有效成分并预测靶点,通过GeneCards、OMIM、PharmGkb和DrugBank数据库获得DMA相关疾病靶标基因,利用Cytoscape软件建立“药物成分-疾病靶点网络”,基于共有靶点使用String数据库构建蛋白质互作网络(PPI),利用David6.7数据库,进行GO功能和KEGG通路富集分析。采用高脂饲料联合尾静脉注射链脲佐菌素(STZ)法建立糖尿病(DM)大鼠模型后进行药物干预。给药10周后检测血糖、足部皮肤血流再灌注量、血液流变学、血清晚期糖基化终产物(AGEs)、肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)水平,HE染色观察眼球、肾脏和足底皮肤组织形态,过典酸雪夫(PAS)染色观察视网膜毛细血管管腔形态,免疫组化法检测肾脏组织中转化生长因子-β1(TGF-β1)的表达情况。结果:筛选养血荣筋丸活性成分103个,PPI网络中关键交集靶点95个,核心基因包括IL-1β、TNF、白细胞介素-10(IL-10)、白细胞介素-6(IL-6)等核心靶点7个,涉及晚期糖基化终产物及其受体(AGE-RAGE)和核因子-κB(NF-κB)等信号通路。动物实验结果显示,在给药后不同时间点,模型组大鼠血糖水平均高于对照组(P<0.01),羟苯磺酸钙组、养血荣筋丸高剂量组、养血荣筋丸中剂量组及养血荣筋丸低剂量组大鼠血糖水平与模型组比较,差异均无统计学意义(P>0.05)。给药干预结束后,模型组大鼠血流灌注量(Flux)低于对照组(P<0.01),全血黏度高于对照组(P<0.01);模型组大鼠眼球视网膜明显增厚,肾小球基底膜样物质增多,管状基底膜增厚,足底皮肤毛细血管增生明显;模型组大鼠血清AGEs、IL-1β、TNF-α水平和肾脏中TGF-β1表达水平均高于对照组(P<0.01);羟苯磺酸钙组、养血荣筋丸高剂量组、养血荣筋丸中剂量组及养血荣筋丸低剂量组大�Objective:To investigate the effect of Yangxue Rongjin pill on diabetic microangiopaopathy(DMA)based on network pharmacology and animal experiments.Methods:TCMSP,ETCM and PubChem databases were used to screen the effective components of Yangxue Rongjin pill and predict the target.The DMA-related disease target genes were obtained from GeneCards,OMIM,PharmGkb and DrugBank databases.The"drug ingredient-disease target network"was established using Cytoscape software,and a String database was used to build a PPI network based on common targets.The enrichment analysis of GO function and KEGG pathway was carried out using David6.7 database.Diabetic rat model was established by high fat diet combined with streptozotocin(STZ)injection through tail vein,and then drug intervention was performed.After 10 weeks of administration,blood glucose level,vascular reperfusion volume of foot skin,blood rheology,serum advanced glycation end products(AGEs),tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)levels were detected.HE staining was used to observe the morphology of eye,kidney and plantar skin tissues,and periodic acid Schiff(PAS)staining was used to observe the morphology of retinal capillary lumens.Immunohistochemistry was used to detect the expression of transforming growth factor-β1(TGF-β1)in kidney tissues.Results:Totally 103 active ingredients of Yangxue Rongjin pill were screened,and 95 key intersection targets were identified in PPI network.Core genes included IL-1β,TNF,interleukin-10(IL-10),interleukin-6(IL-6)and other core targets,which were involved in advanced glycation end products-receptor for advanced glycation end products(AGE-RAGE)and nuclear factor-kappa B(NF-κB)signaling pathways.The experimental results revealed that at various time points after administration,the model group showed higher blood glucose values than control group(P<0.01).Compared with the model group,there was no statistically significant difference in blood glucose levels between the calcium dobesilate group,high-dose Yangxue

关 键 词：糖尿病微血管病变 养血荣筋丸 网络药理学 AGE-RAGE NF-ΚB信号通路 

分 类 号：R285.5[医药卫生—中药学]