BACKGROUND:In recent years,increasing studies have shown that low-intensity pulsed ultrasound can promote the healing of acute tendon injuries,but the specific mechanism is still unclear. OBJECTIVE:To observe the effect of low-intensity pulsed ultrasound on early angiogenesis after acute tendon injury,and to detect the regulatory relationship of low-intensity pulsed ultrasound with vascular endothelial growth factor-related signaling pathways,so as to reveal its potential mechanism of action. METHODS:Animal models of acute Achilles tendon injury were established using local injection of type I collagenase for 3 days in SPF male Sprague-Dawley rats aged 8-12 weeks,and were then randomly divided into ultrasound group and control group.In the ultrasound group,low-intensity pulsed ultrasound was treated daily with a small ultrasonic probe with an effective radiation area of 1 cm2 perpendicular to the Achilles tendon.No intervention was performed in the control group.Ultrasound imaging examination was performed 2 weeks later to observe the early healing of the tendon.Hematoxylin-eosin staining and CD31 immunohistochemical staining were performed to observe the changes in the number of blood vessels in the tissues after 1 and 2 weeks of treatment.The expression of vascular endothelial growth factor-related signaling pathway molecules in Achilles tendon tissues was detected by western blot or qRT-PCR. RESULTS AND CONCLUSION:Compared with the control group,the Achilles tendon in the ultrasound group was more continuous,the echo intensity was lower and more uniform,and the tendon thickness was significantly reduced(P<0.05).Hematoxylin-eosin staining and CD31 immunohistochemical staining results showed that after 2 weeks of treatment,the number of new vessels in the ultrasound group was significantly increased compared with the control group(P<0.05).Western blot and qRT-PCR results showed that after 2 weeks of continuous ultrasound intervention,the protein or mRNA expressions of vascular endothelial growth factor,Yes-associated protein,angiopoietin-2 and cysteine-rich angiogenic inducer 61 in the Achilles tendon of the ultrasound group were significantly higher than those of the control group(P<0.05).These finding indicate that low-intensity pulsed ultrasound significantly increases the number of blood vessels in the early stage of acute tendon injury and accelerate tendon healing by up-regulating vascular endothelial growth factor expression.