Yin Xiao-Dong, Jia Pei-Jie, Pang Yan, He Jing-Hua
Department of Oncology, Tianjin Union Medicine Center, Tianjin, China.
Department of Pharmacology, Basic Medical School, Tianjin Medical University, Tianjin, China.
Curr Ther Res Clin Exp. 2012 Sep;73(4-5):140-9. doi: 10.1016/j.curtheres.2012.07.001.
2-Amino-2-[2-(4-octylphenyl)ethyl] propane-1,3-diol hydrochloride (FTY720) is a novel agent with protective effect on several markers of liver injury. It is a chemical substance derived by modifying myriocin from the ascomycete Isaria sinclairii. It has been reported that FTY720 is able to treat autoimmune encephalomyelitis, renal cancer, asthma, and multiple sclerosis. More potent clinical applications of FTY720 need to be investigated.
The aim of this study was to evaluate the protective effect of FTY720 on several markers of experimental liver injury and to investigate the possible mechanism of action.
Concanavalin A (Con A) at a dose of 15 mg/kg was intravenously. injected in mice, and 10 days before the Con A challenge, 1 mg/kg, 3 mg/kg, and 6 mg/kg of FTY720 were administered to mice. The liver injury was monitored biochemically by measuring serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and tumor necrosis factor-α (TNF-α) levels. TNF-α and nuclear factor-κB (NF-κB) in liver tissue were detected by Western blot analysis.
FTY720, when administered intragastrically for 10 days in mice with Con A-induced liver injury, dose-dependently reduced serum ALT and AST and TNF-α levels. The differences were statistically significant (P ≤ 0.05). It was also found that FTY720 decreases TNF-α and NF-κB protein expression in liver tissue.
FTY720 is able to improve several markers of Con A-induced liver injury in mice, including serum ALT, serum AST, TNF-α, and NF-κB, which might be at least in part related to its ability to reduce TNF-α/NF-κB cascade activity.
2-氨基-2-[2-(4-辛基苯基)乙基]丙烷-1,3-二醇盐酸盐（FTY720）是一种对多种肝损伤标志物具有保护作用的新型药物。它是一种通过修饰来自子囊菌伊斯雷尔链霉菌的嗜球果伞素而衍生的化学物质。据报道，FTY720能够治疗自身免疫性脑脊髓炎、肾癌、哮喘和多发性硬化症。FTY720更有效的临床应用有待研究。
本研究旨在评估FTY720对实验性肝损伤的几种标志物的保护作用，并探讨其可能的作用机制。
以15mg/kg的剂量将刀豆蛋白A（Con A）静脉注射到小鼠体内，在Con A攻击前10天，给小鼠分别给予1mg/kg、3mg/kg和6mg/kg的FTY720。通过测量血清丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）和肿瘤坏死因子-α（TNF-α）水平，对肝损伤进行生化监测。通过蛋白质免疫印迹分析检测肝组织中的TNF-α和核因子-κB（NF-κB）。
在Con A诱导肝损伤的小鼠中，FTY720灌胃给药10天，可剂量依赖性降低血清ALT、AST和TNF-α水平。差异具有统计学意义（P≤0.05）。还发现FTY720可降低肝组织中TNF-α和NF-κB蛋白的表达。
FTY720能够改善Con A诱导的小鼠肝损伤的几种标志物，包括血清ALT、血清AST、TNF-α和NF-κB，这可能至少部分与其降低TNF-α/NF-κB级联活性的能力有关。
