Kim Kil Hwan, Im Hyeon-Woo, Karmacharya Mrigendra Bir, Kim Sejong, Min Byoung-Hyun, Park So Ra, Choi Byung Hyune
Veterans Medical Research Institute, Veterans Health Service Medical Center, Seoul, Republic of Korea.
2Department of Physiology and Biophysics, Inha University College of Medicine, 100 Inha-ro, Nam-gu, Incheon, 22212 Republic of Korea.
J Inflamm (Lond). 2020 Feb 13;17:7. doi: 10.1186/s12950-020-0235-x. eCollection 2020.
Therapeutic potential of low-intensity ultrasound (LIUS) has become evident in various musculoskeletal diseases. We have previously shown that LIUS has an inhibitory effect on local edema in various diseases including the arthritis and brain injury. In this study, we examined whether LIUS can attenuate paw edema formation vis-à-vis vascular permeability and inflammation in rats induced by carrageenan. LIUS with a frequency of 1 MHz and the intensities of 50, 100, or 200 mW/cm were exposed on rat paws for 10 min immediately after carrageenan injection.
Carrageenan injection induced paw edema which was peaked at 6 h and gradually decreased nearly to the initial baseline value after 72 h. LIUS showed a significant reduction of paw edema formation at 2 and 6 h at all intensities tested. The highest reduction was observed at the intensity of 50 mW/cm. Histological analyses confirmed that LIUS clearly decreased the carrageenan-induced swelling of interstitial space under the paw skin and infiltration of polymorphonuclear leukocytes. Moreover, Evans Blue extravasation analyses exhibited a significant decreases of vascular permeability by LIUS. Finally, immunohistochemical staining showed that expression of pro-inflammatory proteins, namely, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) induced by carrageenan injection was reduced back to the normal level after LIUS stimulation.
These results provide a new supporting evidence for LIUS as a therapeutic alternative for the treatment of edema in inflammatory diseases such as cellulitis.
低强度超声(LIUS)在多种肌肉骨骼疾病中的治疗潜力已变得明显。我们之前已经表明,LIUS对包括关节炎和脑损伤在内的各种疾病中的局部水肿具有抑制作用。在本研究中,我们研究了LIUS是否能够减轻角叉菜胶诱导的大鼠爪部水肿形成,以及与之相关的血管通透性和炎症。在注射角叉菜胶后立即将频率为1 MHz、强度为50、100或200 mW/cm²的LIUS照射大鼠爪部10分钟。
注射角叉菜胶诱导爪部水肿,在6小时达到峰值,并在72小时后逐渐降至接近初始基线值。在所有测试强度下,LIUS在2小时和6小时均显示出爪部水肿形成的显著减轻。在50 mW/cm²强度下观察到最大程度的减轻。组织学分析证实,LIUS明显减少了角叉菜胶诱导的爪部皮肤下间质空间肿胀和多形核白细胞浸润。此外,伊文思蓝外渗分析显示LIUS使血管通透性显著降低。最后,免疫组织化学染色表明,角叉菜胶注射诱导的促炎蛋白,即诱导型一氧化氮合酶(iNOS)和环氧化酶-2(COX-2)的表达在LIUS刺激后恢复到正常水平。
这些结果为LIUS作为治疗蜂窝织炎等炎症性疾病水肿的治疗选择提供了新的支持证据。