本研究旨在探讨使用超声波靶向微泡破裂（UTMD）递送托珠单抗并增强其治疗类风湿性关节炎（RA）的疗效的可行性。我们随机将大鼠类风湿性关节炎模型分为五个治疗组：第一组，托珠单抗+微泡（MBs）+ UTMD；第二组，托珠单抗+MBs；第三组，托珠单抗+生理盐水；第四组，MBs+UTMD；第五组，无治疗。我们使用一台商用超声波机，能够使用单个探头同时进行增强超声（CEUS）和UTMD。通过CEUS监测微泡的进入和崩溃。治疗结束后，我们取大鼠左后肢爪部组织进行白细胞介素-6（IL-6）和肿瘤坏死因子α（TNF-α）的免疫组织化学染色。注入药物和微泡的混合物后，患有炎症的后肢爪部区域明显增强，低频超声波照射后立即减弱，并在照射间隔期间再次出现。与第四组和第五组相比，第一、第二和第三组的IL-6表达明显较低（p < 0.01）。第一组的IL-6表达水平最低（p[G1 vs. G2] < 0.01，p[G1 vs. G3] < 0.01）。第一、第二和第三组的TNF-α表达水平显著低于第四和第五组，但在这些组之间的水平差异不明显。UTMD在增强抗IL-6药物治疗RA的疗效方面显示出潜力。版权所有© 2023作者。由Elsevier Inc.出版。保留所有权利。

Our aim was to explore the feasibility of using ultrasound-targeted microbubble destruction (UTMD) to deliver tocilizumab and enhance its efficacy in treating rheumatoid arthritis (RA).Rats with adjuvant-induced arthritis were randomly assigned to one of five treatment groups: group 1, tocilizumab + microbubbles (MBs) + UTMD; group 2, tocilizumab + MBs; group 3, tocilizumab + saline; group 4, MBs + UTMD; group 5, no treatment. We employed a commercially available ultrasound (US) machine capable of performing contrast-enhanced ultrasound (CEUS) and UTMD simultaneously using a single probe. CEUS was performed to monitor the entry and collapse of MBs. After treatment, the rats' left hindlimb paws were harvested for immunohistochemical staining of interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α).After injection of the mixture of drugs and MBs with UTMD, significant enhancement was seen in the inflamed hindlimb paw regions, which subsided immediately on exposure to low-frequency US beams and re-appeared in the intervals between beam exposures. IL-6 expression was significantly lower in groups 1, 2 and 3 than in groups 4 and 5 (p < 0.01). Group 1 had the lowest level of IL-6 expression (p [G1 vs. G2] < 0.01, p [G1 vs. G3] < 0.01). The levels of TNF-α expression in groups 1, 2, and 3 were significantly lower than those in groups 4 and 5, but no difference was observed in these levels between groups 1-3.UTMD shows promise in enhancing the treatment efficacy of anti-IL-6 drugs for RA treatment.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.