通讯作者: 宋永周, yongzhousong@hebmu.edu.cn

DOI：10.12201/bmr.202603.00047

Correlation analysis of lower limb contrast changes and Vasoactive factors levels in diabetic foot rabbit model

• 摘要：目的 通过兔糖尿病足模型,分析不同时期超声造影(contrast-enhanced ultrasound ,CEUS)参数与血清血管内皮生长因子(vascular endothelial growth factor ,VEGF)、C-X-C基序趋化因子-12(C-X-C motif chemokine 12,CXCL-12)水平的相关性,以评估微循环病变情况。方法 10只新西兰大白兔,静脉注射四氧嘧啶诱导高血糖(空腹血糖＞16mmol/L及多饮、多食、多尿症状),再通过磁片压迫法诱发足部溃疡。ELISA法测定正常期、糖尿病(diabetes mellitus ,DM)期、糖尿病足(diabetic foot ulcer ,DFU)期三个不同阶段血清VEGF、CXCL-12水平。CEUS观测腓肠肌微循环参数,定量分析峰值强度(peak intensity ,PI)、曲线下面积(area under the curve ,AUC)、达峰时间(time to peak ,TTP)。结果 兔DM期VEGF、CXCL-12水平显著高于正常期(P<0.01)；DFU期水平略低于DM期(P>0.1),但仍高于正常期。CEUS参数中TTP 、PI、AUC三种指标均呈现DFU期最高,且DM期高于正常期的趋势(其中TTP在DM期与DFU期高度正相关)。相关性分析中,TP、PI 及 AUC 三个超声造影参数均与 VEGF、CXCL12 呈显著正相关(r 0.509–0.649,p＜0.01)。结论 VEGF与CXCL-12在糖尿病应激期显著升高,DFU期略降,提示微循环失代偿；CEUS参数(尤其TTP)可敏感反映微循环障碍,与血管生成因子浓度水平动态相关,为无创评估提供新思路,具有临床转化潜力。

  关键词： 超声造影; 糖尿病足; 生长因子; 微循环

   

  Abstract: Objective To establish a rabbit model of diabetic foot and explore the correlation between contrast-enhanced ultrasound (CEUS) related parameters and serum levels of vascular endothelial growth factor (VEGF) and C-X-C motif chemokine 12 (CXCL-12) at different disease stages, thereby providing experimental evidence for the objective evaluation of the severity and progression of microcirculatory lesions in diabetic foot. Methods Ten healthy New Zealand white rabbits were selected, and hyperglycemia was induced by intravenous injection of alloxan (with the modeling success criteria defined as fasting blood glucose > 16 mmol/L accompanied by the typical symptoms of polydipsia, polyphagia, and polyuria). Subsequently, foot ulcers were induced via the magnetic disc compression method to establish a rabbit model of diabetic foot (DFU). At three time points (the normal phase, diabetes mellitus (DM) phase, and DFU phase), enzyme-linked immunosorbent assay (ELISA) was used to determine the serum levels of vascular endothelial growth factor (VEGF) and C-X-C motif chemokine 12 (CXCL-12). Meanwhile, contrast-enhanced ultrasound (CEUS) was performed to observe the microcirculatory status of the gastrocnemius muscle, with quantitative analysis of three core parameters: peak intensity (PI), area under the curve (AUC), and time to peak (TTP). Results Serum VEGF and CXCL-12 levels were significantly higher in the DM phase than in the normal phase (P<0.01), slightly lower in the DFU phase (P>0.1) but still higher than normal (P<0.05). CEUS parameters (TTP, PI, AUC) showed the highest values in the DFU phase and higher in the DM phase than normal, with TTP highly positively correlated between DM and DFU phases. Correlation analysis revealed significant positive correlations of TTP, PI, AUC with VEGF and CXCL-12 (r=0.509–0.649, P<0.01). Conclusion Serum VEGF and CXCL-12 are significantly elevated in the DM phase and slightly decreased but still above normal in the DFU phase, suggesting microcirculatory decompensation. CEUS parameters (especially TTP) can sensitively reflect microcirculatory disorders and dynamically correlate with angiogenesis-related factors (VEGF, CXCL-12), offering new insights for non-invasive evaluation of diabetic foot and holding potential for clinical translation.

  Key words: ultrasound contrast, diabetic foot, growth factors, microcirculation; ; ; 

  提交时间：2026-03-12

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• 序号	提交日期	编号	操作
  1	2026-01-14	10.12201/bmr.202603.00047V1	下载

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