Tanaka Y, Takahashi A, Kobayashi K, Arai I, Higuchi S, Otomo S, Wei H L, Liu G T
Department of Pharmacology, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
Arch Int Pharmacodyn Ther. 1995 Mar-Apr;329(2):319-30.
The hepatoprotective effect of SY-640 on Propionibacterium acnes and lipopolysaccharide-induced liver injury in mice and its protective mechanism were examined. Oral administration of SY-640, 150 mg/kg once daily for 7 days, significantly inhibited Propionibacterium acnes and lipopolysaccharide-induced liver injury, but a single administration was without effect. Liver-infiltrating cells (T-lymphocytes and macrophages) play an important role in Propionibacterium and lipopolysaccharide-induced liver injury and express a higher level of leukocyte function-associated antigen-1. SY-640 inhibited the number of liver-infiltrating cells and attenuated the increased expression of leukocyte function-associated antigen-1 on these cells. Tumor necrosis factor-alpha mediated Propionibacterium acnes and lipopolysaccharide-induced liver injury, and SY-640 inhibited the elevation of the serum tumor necrosis factor-alpha concentration after injection of lipopolysaccharide in Propionibacterium acnes-primed mice. The putative effects of SY-640 are inhibitory effects on infiltration into the liver and on activation of T-lymphocytes and macrophages after Propionibacterium acnes-priming, and attenuation of expression of cell adhesion molecules such as leukocyte function-associated antigen-1. The immunological effect of SY-640 is likely to be closely related to the inhibition of Propionibacterium and lipopolysaccharide-induced liver injury.
研究了SY-640对痤疮丙酸杆菌和脂多糖诱导的小鼠肝损伤的保肝作用及其保护机制。口服SY-640，剂量为150mg/kg，每日1次，连续7天，可显著抑制痤疮丙酸杆菌和脂多糖诱导的肝损伤，但单次给药无效。肝浸润细胞（T淋巴细胞和巨噬细胞）在痤疮丙酸杆菌和脂多糖诱导的肝损伤中起重要作用，并表达较高水平的白细胞功能相关抗原-1。SY-640可抑制肝浸润细胞数量，并减弱这些细胞上白细胞功能相关抗原-1表达的增加。肿瘤坏死因子-α介导痤疮丙酸杆菌和脂多糖诱导的肝损伤，SY-640可抑制在痤疮丙酸杆菌致敏小鼠注射脂多糖后血清肿瘤坏死因子-α浓度的升高。SY-640的假定作用是对痤疮丙酸杆菌致敏后肝浸润以及T淋巴细胞和巨噬细胞激活的抑制作用，以及减弱细胞黏附分子如白细胞功能相关抗原-1的表达。SY-640的免疫作用可能与抑制痤疮丙酸杆菌和脂多糖诱导的肝损伤密切相关。
