Effect Of Ultrasound-mediated Oxygen And Paclitaxel-loaded Lipid Microbubbles On Rheumatoid Arthritis Rats

Part One: Biocompatibility of Oxygen and Paclitaxel-loaded Lipid Microbubbles and Selection of a Optimum Irradiation Parameter of Ultrasound in VivoObjectives: To investigate the biocompatibility of oxygen and paclitaxel-loaded lipid microbubbles(OPLMBs) in rat joint, and select a optimum irradiation parameter of ultrasound in vivo.Methods: Five female SD rats were intraarticular injected with OPLMBs in left knee joint, and the other knee joint was injected with normal saline as the control, the basic situations of rats were observed and the changes of the diameter of knee jiont were record, the knee joints were made into pathological sections for observation after a week. Twelve female SD rats were randomly divided into six group after intraarticular injected with OPLMBs, and respectively irradiated by ultrasound with different intensity and times,joint fluid was extracted and destructions of OPLMBs were observed under light microscope.Results: Significant changes of the diameter of knee joint were not observed after intraarticular injection with OPLMBs, no inflammatory cell infiltration was found in histological sections. The ultrasonic irradiation caused varying degrees of destruction of the OPLMBs, the optimum irradiation parameter of ultrasound was 2w/cm2, 300 s.Conclusions: The OPLMBs had a good biocompatibility in rat joint without inflammation-causing effects. The OPLMBs can be destructed by ultrasound with a optimum irradiation parameter of 2w/cm2,300 s.Part Two: Effect of Ultrasound-mediated Oxygen and Paclitaxel-loaded Lipid Microbubbles on CIA RatsObjectives: To investigate the effect of ultrasound-mediated oxygen and paclitaxel-loaded lipid microbubbled on CIA rats and it’s mechanisms, to provide experimental basis for the target therapy of rheumatoid arthritis.Methods: CIA rats model were established, and randomly divided into: B. Model group; C.PTX group; D.US group; E.OLMBs group; F.OPLMBs group; G. OPLMBs +US group; H.MTX group. and Normol group was set at same time. The knee joints were injected with saline or corresponding lipid microbubbles, and joint external ultrasound intervention. The general situations of rats were observed, the changes of body weight and the diameter of the knee joint were recorded, and the joint swelling index was calculated. After the last treatment, knee joints were collected, histological sections were made and observed, the expression of HIF-1α and VEGF in synovial tissue were assayed by Western Blot, the level of IL-6 and TNF-α in joint fluid was detected by Elisa, and the expression of α-SMA was detected by immunohistochemistry method.Results: The CIA rats model were success established. OPLMBs+US can significantly supressed swelling and inflammation of joint, decreased the level of IL-6 and TNF-α in joint fluid, inhibit the expression of HIF-1α、VEGF and α-SMA in synovial tissue.Conclusions: Ultrasound mediated oxygen and paclitaxel-loaded lipid microbubbles can significantly inhibit the arthritis degree of CIA rats, the mechanism may be related to inhibition of synovial cell activation and proliferation, reduced the production of TNF-α and IL-6 in arthritic lesions, depressed the expression of HIF-1α,VEGF and α-SMA in synovial, inhibited joint pannus formation. This study provide experimental basis for the target treatment of rheumatoid arthritis, and provide new method for the treatment of rheumatoid arthritis.