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

Corresponding author: SONG YONG ZHOU, yongzhousong@hebmu.edu.cn

DOI: 10.12201/bmr.202603.00047

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  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; ; ; 

  Submit time: 12 March 2026

  Copyright: The copyright holder for this preprint is the author/funder, who has granted biomedRxiv a license to display the preprint in perpetuity.
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