Background 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/cm2 were exposed on rat paws for 10 min immediately after carrageenan injection. Results 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/cm2. 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. Conclusions These results provide a new supporting evidence for LIUS as a therapeutic alternative for the treatment of edema in inflammatory diseases such as cellulitis.

中文翻译：

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低强度超声可减轻大鼠角叉菜胶注射引起的爪水肿形成并降低血管通透性。

背景 低强度超声 (LIUS) 的治疗潜力已在各种肌肉骨骼疾病中变得明显。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的局部水肿具有抑制作用。在这项研究中，我们检查了 LIUS 是否可以减轻角叉菜胶诱导的大鼠爪水肿形成与血管通透性和炎症的关系。注射角叉菜胶后立即将 1 MHz 频率和 50、100 或 200 mW/cm2 强度的 LIUS 暴露在大鼠爪子上 10 分钟。结果角叉菜胶注射引起的足爪水肿在6 h达到高峰，72 h后逐渐下降至接近初始基线值。在所有测试强度下，LIUS 在 2 小时和 6 小时显示爪水肿形成显着减少。在 50 mW/cm2 的强度下观察到最大的减少。组织学分析证实，LIUS 明显减少了角叉菜胶引起的爪子皮肤下间质空间的肿胀和多形核白细胞的浸润。此外，埃文斯蓝外渗分析显示 LIUS 显着降低了血管通透性。最后，免疫组化染色显示，LIUS 刺激后，角叉菜胶注射诱导的促炎蛋白，即诱导型一氧化氮合酶 (iNOS) 和环氧合酶-2 (COX-2) 的表达降低至正常水平。结论 这些结果为 LIUS 作为治疗蜂窝织炎等炎症性疾病水肿的替代疗法提供了新的支持性证据。组织学分析证实，LIUS 明显减少了角叉菜胶引起的爪子皮肤下间质空间的肿胀和多形核白细胞的浸润。此外，埃文斯蓝外渗分析显示 LIUS 显着降低了血管通透性。最后，免疫组化染色显示，LIUS 刺激后，角叉菜胶注射诱导的促炎蛋白，即诱导型一氧化氮合酶 (iNOS) 和环氧合酶-2 (COX-2) 的表达降低至正常水平。结论 这些结果为 LIUS 作为治疗蜂窝织炎等炎症性疾病水肿的替代疗法提供了新的支持性证据。组织学分析证实，LIUS 明显减少了角叉菜胶引起的爪子皮肤下间质空间的肿胀和多形核白细胞的浸润。此外，埃文斯蓝外渗分析显示 LIUS 显着降低了血管通透性。最后，免疫组化染色显示，LIUS 刺激后，角叉菜胶注射诱导的促炎蛋白，即诱导型一氧化氮合酶 (iNOS) 和环氧合酶-2 (COX-2) 的表达降低至正常水平。结论 这些结果为 LIUS 作为治疗蜂窝织炎等炎症性疾病水肿的替代疗法提供了新的支持性证据。