Effect Of Ultrasound-mediated Oxygen And Paclitaxel-loaded Lipid Microbubbles On Hypoxic Macrophages

In the pathophysiology of rheumatoid arthritis, macrophage recruitment and proliferation of synovial macrophage-like phenotype changes in hypoxic environment interactions play an important role.Paclitaxel as first-line clinical anticancer drugs, there is a certain degree of cytotoxicity. Paclitaxel can improve the collagen-induced animal model of joint swelling, inflammation, inhibit synovial proliferation and the generation of pannus. Ultrasound targeted microbubble destruction technology(UTMD) can make the appropriate medication and oxygen to produce pharmacological effects in the site of administration, on the other hand, it can increase the ingestion of drugs, improve efficacy. In this study,the construction of hypoxia model of macrophages was constructed.Ultrasound irradiation with oxygen and paclitaxel loaded liposome microbubbles as a means of intervention. The effect of this method on the activity of hypoxia macrophage and the improvement of hypoxia state were observed. We found that:(1) the suitable conditions of chemical inductionand physical induction can induce the hypoxia status of macrophages.(2)ultrasound mediated oxygen and paclitaxel loaded liposome microbubbles can inhibit the cell activity of hypoxia macrophage, and cause apoptosis of hypoxia macrophage.(3) this method can down regulate the expression of hypoxia inducible factor-1 alpha gene and protein level.In summary, this method can inhibit the proliferation of hypoxic macrophages, can improve the hypoxia status of macrophages and down regulate the expression of hypoxia inducible factor.