Microbubble-enhanced ultrasound exposure promotes uptake of methotrexate into synovial cells and enhanced antiinflammatory effects in the knees of rabbits with antigen-induced arthritis
Microbubble-enhanced ultrasound exposure promotes uptake of methotrexate into synovial cells and enhanced antiinflammatory effects in the knees of rabbits with antigen-induced arthritis
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DOI：
10.1002/art.21154
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发表时间：
2005-08-01
影响因子：
--
通讯作者：
Wakitani, S
中科院分区：
文献类型：
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作者：
Nakaya, H;Shimizu, T;Wakitani, S
Objective.评估微泡增强超声（US）治疗是否促进甲氨蝶呤（MTX）递送到滑膜细胞中以及在兔关节炎模型中关节内MTX治疗的增强的滑膜作用。用卵清蛋白免疫家兔53只，诱发双侧膝关节炎。然后将包括微泡剂的MTX注射到左和右膝关节中，并且右膝暴露于US（MTX+/US+组），而左膝不暴露于US（MTX+/US-组）。在5个时间点对7只家兔的膝关节进行组织学评价，直至第56天。在第7天和第28天测量滑膜组织中白细胞介素-1 β（IL-1 β）的定量基因表达。8只家兔于治疗后12小时测定滑膜组织中MTX浓度。为评价微泡造影剂增强超声在无甲氨蝶呤（MTX）情况下的治疗效果，将微泡造影剂分别注入10只家兔的左、右膝关节，观察第7、28天的组织学变化。MTX+/US+组滑膜组织中MTX浓度显著高于MTX+/US-组。从组织学评价结果和滑膜组织中IL-1 β基因表达水平判断，MTX+/US+组的滑膜炎症较MTX+/US-组不明显。微泡增强超声暴露本身似乎也不会影响炎症。微泡增强的US暴露促进MTX摄取到滑膜细胞中，这导致关节内注射MTX的抗肿瘤作用增强。这些结果表明，该技术的应用可能具有临床益处。
Objective. To evaluate whether microbubble-enhanced ultrasound (US) treatment promotes the delivery of methotrexate (MTX) into synovial cells and the enhanced antiinflammatory effects of intraarticular MTX therapy in a rabbit arthritis model.Methods. Arthritis was induced in both knees of 53 rabbits by immunization with ovalbumin. MTX including a microbubble agent was then injected into the left and right knee joints, and the right knees were exposed to US (MTX+/US+ group), while the left knees were not (MTX+/US- group). The knee joints were evaluated histologically in 7 rabbits at 5 time points up to day 56. Quantitative gene expression of interleukin-1 beta (IL-1 beta) in synovial tissue was measured on days 7 and 28. Eight rabbits were used for the measurement of MTX concentration in synovial tissue 12 hours after treatment. To evaluate the effect of microbubble-enhanced US treatment in the absence of MTX, only the microbubble agent was injected into the left and right knee joints of 10 rabbits with or without US exposure, and these animals were evaluated histologically on days 7 and 28.Results. The MTX concentration in synovial tissue was significantly higher in the MTX+/US+ group than in the MTX+/US- group. Synovial inflammation was less prominent in the MTX+/US+ group compared with the MTX+/US- group, judging from the results of the histologic evaluation and the gene expression levels of IL-1 beta in synovial tissue. It also appeared that microbubble-enhanced US exposure itself did not affect inflammation.Conclusion. Microbubble-enhanced US exposure promoted the uptake of MTX into synovial cells, which resulted in enhancement of the antiinflammatory effects of the intraarticular MTX injection. These results suggest that application of this technique may have clinical benefit.