Department of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka, Japan.
Department of Pharmacy, Aizenbashi Hospital, Osaka City, Osaka, Japan.
Pediatr Int. 2022 Jan;64(1):e15153. doi: 10.1111/ped.15153.
We investigated the efficacy of sivelestat sodium hydrate (SSH) as a treatment for Kawasaki disease, and its pharmacological action sites, in mice with Candida albicans water-soluble fraction-induced vasculitis.
Sivelestat sodium hydrate was administered intraperitoneally to Candida albicans water-soluble fraction-induced vasculitis model mice to assess its efficacy in preventing the development of coronary artery lesions based on the degree of inflammatory cell infiltration in the aortic root and coronary arteries (vasculitis score). The pharmacological sites of action were investigated based on changes in neutrophil elastase (NE) and intercellular adhesion molecule 1 (ICAM-1) positive areas, ICAM-1 and tumor necrosis factor-α mRNA expression levels in the upper heart, and the proportion of monocytes in the peripheral blood.
The vasculitis score decreased below the lower limit of the 95% confidence interval of untreated mice in 69% of the SSH-treated mice. The NE- and ICAM-1-positive regions, and the mRNA expression of ICAM-1 and tumor necrosis factor-α were lower in the SSH-treated mice than in the untreated mice. The proportion of monocytes in the peripheral blood was higher in the SSH-treated mice than in the untreated mice, whereas monocyte migration to inflammation areas was suppressed in the SSH-treated mice.
Our results showed that SSH might prevent the development of coronary artery lesions and ameliorate disease activity. In addition to its NE-inhibitory effect, SSH sites of action may also include monocytes.
我们研究了磺酸钠水合物（SSH）治疗白色念珠菌水溶性部分诱导的血管炎小鼠川崎病的疗效及其作用部位。
SSH 腹腔注射白色念珠菌水溶性部分诱导的血管炎模型小鼠，根据主动脉根部和冠状动脉炎症细胞浸润程度（血管炎评分）评估其预防冠状动脉损伤的疗效。根据中性粒细胞弹性蛋白酶（NE）和细胞间黏附分子 1（ICAM-1）阳性面积、心脏上部 ICAM-1 和肿瘤坏死因子-α mRNA 表达水平以及外周血单核细胞比例的变化，探讨其作用部位。
在 SSH 治疗的小鼠中，69%的血管炎评分低于未治疗小鼠的 95%置信区间下限。与未治疗组相比，SSH 治疗组的 NE 和 ICAM-1 阳性区域以及 ICAM-1 和肿瘤坏死因子-α 的 mRNA 表达降低。外周血单核细胞比例在 SSH 治疗组高于未治疗组，而 SSH 治疗组单核细胞向炎症部位迁移受到抑制。
我们的结果表明 SSH 可能预防冠状动脉损伤的发展并改善疾病活动。除了其 NE 抑制作用外，SSH 的作用部位可能还包括单核细胞。
