Ultrasound stimulated microbubbles cavitation enhanced the therapeutic effect of colchicine in rats with acute gouty arthritis

Abstract Objective To investigate whether cavitation induced by ultrasound stimulated microbubbles (USMB) can enhance the therapeutic effect of colchicine and reduce its side effects on acute gouty arthritis (AGA) in rats. Materials and Methods Each rat underwent right ankle joint contrast-enhanced ultrasound (CEUS) before and following cavitation treatment. The area under the curve (AUC) of CEUS before and after cavitation and among groups were compared to contrast the impact on blood perfusion of the ankle joint in rats with cavitation. The symptoms of AGA were evaluated based on 24-hour ankle joint swelling degree and gait score. The infiltration of neutrophils was assessed using the Hematoxylin-eosin(HE)staining, while the inflammation and dilation of blood vessels were measured by and plasma interleukin-1β (IL-1β) and endothelial nitric oxide synthase (eNOS). Moreover, the magnitude of side effects was analyzed by gastrointestinal reaction score. Results The AUC after cavitation induced by USMB were significantly higher than those before cavitation. When compared with groups without cavitation, the AUC were markedly higher in groups treated with cavitation (all p<0.01). In groups treated with cavitation combined with colchicine, the degree of ankle swelling, gait scores, and the level of plasma IL-1β in AGA rats were lower, while the concentration of plasma eNOS was higher, group treated with colchicine alone (all p<0.05). HE staining showed that cavitation combined with colchicine helped to reduce the neutrophil synovial infiltration of ankle joint and decrease the gastrointestinal reaction score in rats with AGA. Compared with the three groups receiving drug treatment, the incidence of gastrointestinal reaction score in the low concentration group was significantly lower than that in the high concentration groups (all p<0.05). Conclusion The cavitation induced by USMB could significantly enhance the blood perfusion of ankle joint in rats with AGA, leading to the increase in therapeutic effect of colchicine and reduce the dose used of colchicine, thus minimizing the side effects associated with it.