中国中医药信息杂志2026，Vol.33Issue(6)：28-37,10.DOI:10.19879/j.cnki.1005-5304.202511121
丹瓜护脉口服液通过HIF-1α调控铜死亡保护2型糖尿病血管内皮细胞的机制研究
Study on the Mechanism of Dangua Humai Oral Liquid in Improving Copper Death of Vascular Endothelial Cells in Type 2 Diabetic via HIF-1α
摘要
Abstract
Objective To investigate the mechanism of Dangua Humai Oral Liquid(DGHM)in improving copper death(cuproptosis)of vascular endothelial cells in type 2 diabetes mellitus(T2DM)rats through hypoxia-inducible factor-1α(HIF-1α).Methods Network pharmacology was used to screen the active components,potential targets of DGHM,and its intersection targets with T2DM and oxidative stress.Protein-protein interaction network construction and GO and KEGG enrichment analyses were performed.A T2DM rat model was induced by a high-fat and high-sucrose diet combined with streptozotocin injection.The rats were randomly divided into normal group,model group,DGHM group,HIF-1α inhibitor(PX-478)group,DGHM combined with PX-478 group,and Metformin control group.After 14 weeks of intervention,glycolipid metabolism indicators including FBG,2 hBG,HbA1c,TC,TG,HDL-C and LDL-C were assessed by biochemical methods and ELISA;the morphological structure of the thoracic aorta was observed by HE staining;HIF-1α protein expression in thoracic aortic tissue was detected by immunohistochemistry;vascular endothelial function and oxidative stress markers including endothelin-1(ET-1),vascular endothelial growth factor(VEGF),Caspase-3 and nitric oxide synthase(NOS)were measured by ELISA;copper deposition was detected by rubeanic acid staining.Results Network pharmacology identified 224 intersection targets with T2DM and oxidative stress,with HIF-1α being one of the core targets.Animal experiments showed that DGHM could significantly reduce FBG,2 hBG,HbA1c,TC,TG,LDL-C,ET-1 and Caspase-3 levels,increase HDL-C,VEGF,NOS activity,and HIF-1α protein expression of model rats(P<0.05,P<0.01,P<0.001),and alleviate structural damage and copper deposition in the thoracic aortic endothelium.After inhibition of HIF-1α,glucose and lipid metabolism disorders,oxidative stress,abnormal copper ion aggregation,and vascular endothelial damage worsened.The combination of DGHM and PX-478 could improve to some extent the glucose and lipid metabolism disorders,oxidative stress,and copper overload caused by PX-478.Conclusion DGHM may exert a protective effect on T2DM vascular endothelium by upregulating HIF-1α expression,reducing abnormal accumulation of copper ions,inhibiting copper death process,alleviating oxidative stress caused by it.关键词
2型糖尿病/丹瓜护脉口服液/网络药理学/缺氧诱导因子-1α/氧化应激/铜死亡Key words
type 2 diabetes mellitus/Dangua Humai Oral Liquid/network pharmacology/hypoxia-inducible factor-1α/oxidative stress/cuproptosis分类
医药卫生引用本文复制引用
靳霖溪,何卫东,王志塔,陈奇炜,韩壮,姚淑红,阮怡,洪鑫淼,衡先培,杨柳清,李亮..丹瓜护脉口服液通过HIF-1α调控铜死亡保护2型糖尿病血管内皮细胞的机制研究[J].中国中医药信息杂志,2026,33(6):28-37,10.基金项目
国家自然科学基金(82205071、82074308、82274389) （82205071、82074308、82274389）
福建省自然科学基金(2023J01149、2023J01844、2024J01771、2024J01758) （2023J01149、2023J01844、2024J01771、2024J01758）
