超音波造影剤が主要臓器に及ぼす影響—小動物を用いた検討—

Takuya Abe; 阿部拓也; Yutaka Fujii; 藤井豊; Haruo Hanawa; 塙晴雄; Kikuo Ikegami; 池上喜久夫; Hiroaki Watanabe; 渡邊博昭

doi:10.11272/jss.420

超音波造影剤が主要臓器に及ぼす影響—小動物を用いた検討—Effects of Ultrasound Contrast Agents on Major Organs: A Study Using Small Animals

阿部拓也¹，藤井豊¹，塙晴雄¹，池上喜久夫²，渡邊博昭¹Takuya Abe¹, Yutaka Fujii¹, Haruo Hanawa¹, Kikuo Ikegami², Hiroaki Watanabe¹

¹ 新潟医療福祉大学医療技術学部臨床技術学科Niigata University of Health and Welfare, Faculty of Medical Technology, Department of Clinical Engineering and Medical Technology

² 千葉科学大学危機管理学部保健医療学科Chiba Institute of Science, Faculty of Risk and Crisis Management, Department of Health and Medical Sciences

受付日：2023年8月28日Received: August 28, 2023

受理日：2024年1月24日Accepted: January 24, 2024

発行日：2024年6月1日Published: June 1, 2024

目的：超音波造影剤（Ultrasound Contrast Agents: UCA）は，開発時に炎症が確認されているなど，UCA投与の潜在的な有害作用，特に臓器局所への有害作用に関する懸念が残っている．本研究では，UCA投与における炎症性遺伝子の発現に焦点を当て，主要臓器に及ぼす影響を評価した．

対象と方法：Sprague-Dawleyラットを用い，UCA投与群とControl群に分けた．UCA投与（Sonazoid^®，0.015 mL/kg）後に10分間超音波照射した．Control群にはUCA投与の代わりに，生理食塩水を0.015 mL/kg投与した．その後，主要臓器（心臓・肺・肝臓・腎臓）を摘出し，MCP-1, IL-6, IL-10, TNF-αの遺伝子発現を評価した．

結果と考察：UCA投与群では，Control群と比較してすべての臓器でMCP-1, IL-6, IL-10が有意に高値を示した．TNF-αは肝臓と肺で有意な高値を示した．この結果から，UCA投与により臓器局所での炎症が惹起され，特に肝臓および肺における傷害が顕著であることを明らかにした．毛細血管内でUCAのマイクロバブルが滞留・集積し，血管内皮傷害などが要因で炎症を惹起している可能性がある．

結論：本研究は，UCA投与における主要臓器局所への弊害の新たな知見を提示した．UCA投与による炎症性遺伝子の発現は主要臓器局所で増加し，その傷害は特に肝臓および肺において顕著であることが確認された．

Purpose: Concerns remain regarding the potential adverse effects of ultrasound contrast agents (UCA), particularly on local organs, following the identification of inflammation during the development of these agents. This study examined the expression of inflammatory genes in major organs during UCA administration and assessed their effect.

Subjects and Methods: Sprague-Dawley rats were divided into the UCA group (Sonazoid^®, 0.015 mL/kg), which received subsequent ultrasound irradiation for 10 min, and control group, which received 0.015 mL/kg of saline instead of UCA. Major organs (heart, lungs, liver, and kidneys) were excised, and the expression of monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha (TNF-α) was evaluated.

Results and Discussion: Significantly higher levels of expression of MCP-1, IL-6, and IL-10 were observed in all organs within the UCA-treated group than in the control group, with TNF-α significantly elevated in the liver and lungs. These findings suggest that UCA administration triggers local inflammation in organs, specifically in the liver and lungs. UCA microbubble accumulation within capillaries may induce inflammation via vascular endothelial injury.

Conclusions: This study provides novel insights into the adverse effects of UCA administration on major organ localization, confirming increased inflammatory gene expression induced by UCA in major organs. Notably, the liver and lungs demonstrate more pronounced effects.

Key words: Contrast enhanced ultrasonography; Sonazoid^®; microbubbles; allowable pressure; inflammation

超音波検査技術

研究Research Paper

超音波造影剤が主要臓器に及ぼす影響—小動物を用いた検討—Effects of Ultrasound Contrast Agents on Major Organs: A Study Using Small Animals