Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Minamitamagaki-cho 3500-3, Suzuka 513-8670, Mie, Japan.
Konan Chemical Manufacturing, Co., Ltd., 1515 Kitagomizuka, Yokkaichi 510-0103, Mie, Japan.
Mar Drugs. 2022 Feb 3;20(2):121. doi: 10.3390/md20020121.
We previously reported that rhamnan sulfate (RS) purified from significantly suppressed lipopolysaccharide (LPS)-induced inflammation in cultured human vascular endothelial cells. Here, we analyzed the effect of orally administered RS on LPS-induced damage to mouse organs and vascular endothelium. RS (1 mg) was orally administered daily to BALB/c mice, 50 μg of LPS was intraperitoneally administered on day 8, and Evans blue was injected into the tail vein 6 h later. After 30 min, LPS-treated mice showed pulmonary Evans blue leakage and elevated plasma levels of liver damage markers, whereas this reaction was suppressed in LPS + RS-treated mice. Immunohistochemical and Western blot analysis of mouse organs 24 h after LPS treatment showed significant neutrophil infiltration into the lung, liver, and jejunum tissues of LPS-treated mice and high expression levels of inflammation-related factors in these tissues. Expression levels of these factors were significantly suppressed in LPS + RS-treated mice. Analysis of lung glycocalyx showed a significant reduction in glycocalyx in LPS-treated mice but not in LPS + RS-treated mice. Levels of syndecan-4, one of the glycocalyx components, decreased in LPS-treated mice and increased in LPS + RS-treated mice. The current results suggest that orally administered RS protects organs and vascular endothelium from LPS-induced inflammation and maintains blood circulation.
我们之前曾报道过,从 中提取的鼠李糖硫酸酯(RS)可显著抑制培养的人血管内皮细胞中脂多糖(LPS)诱导的炎症。在这里,我们分析了口服 RS 对 LPS 诱导的小鼠器官和血管内皮损伤的影响。RS(1mg)每天口服给予 BALB/c 小鼠,第 8 天腹腔内给予 50μg LPS,并在 6 小时后尾静脉注射 Evans 蓝。30 分钟后,LPS 处理的小鼠表现出肺部 Evans 蓝泄漏和肝损伤标志物的血浆水平升高,而 LPS+RS 处理的小鼠则抑制了这种反应。LPS 处理后 24 小时对小鼠器官进行免疫组织化学和 Western blot 分析显示,LPS 处理的小鼠肺部、肝脏和空肠组织中有明显的中性粒细胞浸润,这些组织中炎症相关因子的表达水平较高。LPS+RS 处理的小鼠这些因子的表达水平明显受到抑制。对肺糖萼的分析表明,LPS 处理的小鼠肺糖萼显著减少,但 LPS+RS 处理的小鼠则没有。LPS 处理的小鼠中糖萼的一种成分硫酸乙酰肝素-4(syndecan-4)水平降低,而 LPS+RS 处理的小鼠中则增加。目前的结果表明,口服 RS 可保护器官和血管内皮免受 LPS 诱导的炎症,并维持血液循环。