Contrast-enhanced ultrasonography is a valid technique for the assessment of renal microvascular perfusion dysfunction in diabetic Goto-Kakizaki rats

摘要

Aim: To evaluate the reliability of contrast-enhanced ultrasonography (CEUS) for the detection of renal microvascular blood perfusion in a type 2 diabetic Goto-Kakizaki (GK) rat model. Methods: Male GK and Wistar rats at the age of 4, 12 and 20 weeks (n = 10, respectively) were used for the study. Real-time and haemodynamic imaging of the renal cortex was performed using CEUS with SonoVue. Outage time-intensity curves (TICs) were applied for the analysis of basic intensity, slope rates of the ascending (S1) and descending curves (S2), time to peak (TTP), half time of peak descending (HDT), peak intensity (PI), and total area under the curve (AUC). Immunohistochemical staining for endothelial cells (ECs) was performed using the CD34 monoclonal antibody for the quantification of microvessel density and distribution. Results: Images of the renal cortex microvascular beds after injection of SonoVue in the rats were rapidly and clearly displayed, and it is easy to differentiate the enhanced and faded images of renal perfusion. The TICs of the GK rats were much wider than the controls; however, no significant changes in PI were found in all aged rats. Ultrasonographic quantitative analysis revealed a decrease in S1 and S2, and an increase in TTP, HDT and AUC in the 12- and 20-week-old GK rats compared with the controls (P < 0.05). Moreover, the 20-week-old GK rats had much lower glomerular density and smaller distribution area of CD34-positive ECs, which was in parallel with more severe proteinuria, GBM thickening, glomerulosclerosis and interstitial vascular damages (P < 0.05). Interestingly, negative correlations between AUC and glomerular microvessel density or distribution were detected, respectively (P < 0.05). Conclusions: Contrast-enhanced ultrasonography is a valid technique for the real-time and dynamic assessment of renal cortex microvascular perfusion and haemodynamic characterization in GK rats.