河北中医药学报2025，Vol.40Issue(6)：1-7,13,8.
当归四逆汤对糖尿病重度肢体缺血小鼠后肢血流灌注的影响
Effect of Danggui Sini Decoction on Hindlimb Blood Perfusion in Diabetic Mice with Critical Limb Ischemia
摘要
Abstract
Objective:To investigate the effects of Danggui Sini Decoction(DSD)on hindlimb blood perfusion and its underlying mechanisms in diabetic mice with critical limb ischemia(CLI).Methods:Diabetic mice were induced by streptozotocin,followed by femoral artery/vein ligation to establish CLI.Successfully modeled mice were randomized into model group,cilostazol group,DSD high-/low-dose groups,with an additional normal controls.Each dosing group was administered the corresponding drug by gavage,while the control group and model group were given normal saline.After 14-day interventions,the hindlimb function and blood flow re-covery were evaluated by means of swimming endurance test and laser Doppler flow imaging.HE staining and immunofluorescence as-say were used to observe the tissue morphology of the ischemic gastrocnemius muscle and the expression of platelet endothelial cell ad-hesion molecule-1(CD31).ELISA was performed to detect the serum levels of endothelin-1(ET-1)and endothelial nitric oxide syn-thase(eNOS).Western blot analysis was conducted to assess the activation status of the vascular endothelial growth factor(VEGF)/phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)pathway.Results:Compared with the control group,the mice in the model group showed persistent hyperglycemia,shortened swimming time,reduced blood perfusion in the hind limbs,ischemic muscle tissue injury,compensatory increase in capillary density,imbalance of serum ET-1/eNOS,and partial activation of the VEGF/PI3K/AKT pathway(P<0.05);Compared with the model group,DSD groups showed prolonged swimming time(P<0.05),elevated ische-mic/normal limb blood perfusion ratio(P<0.05),reduced inflammatory infiltration,and increased CD31-positive cells(P<0.05).Serum ET-1 decreased(P<0.05)while eNOS increased(P<0.05).DSD upregulated VEGFA expression(P<0.05)and enhanced phosphorylation of VEGFR2,PI3K p85,and AKT1(P<0.05).Conclusion:DSD can improve blood perfusion in ischemic lower limbs in diabetes.The mechanism may be related to regulating endothelial function(ET-1/eNOS balance)and activating the VEGF/PI3K/AKT pathway to promote angiogenesis.关键词
当归四逆汤/糖尿病/重度肢体缺血/血流灌注/血管新生/内皮素-1/内皮型一氧化氮合成酶/VEGF/PI3K/AKT信号通路Key words
Danggui Sini Decoction/diabetes/critical limb ischemia/blood perfusion/angiogenesis/ET-1/eNOS/VEGF/PI3K/AKT pathway分类
医药卫生引用本文复制引用
LIU Zhiqiang,ZHANG Qian,ZHU Chaojun,LI Xiaolin,JING Jinpeng,DAI Rui,LIU Wei,WEI Qiuyan..当归四逆汤对糖尿病重度肢体缺血小鼠后肢血流灌注的影响[J].河北中医药学报,2025,40(6):1-7,13,8.基金项目
国家自然科学基金(81973853) （81973853）
天津市教委科研计划项目(2021KJ154) （2021KJ154）
