Supawadee Sukseree, Thanet Sophonnithiprasert, Wisut Pradidarcheep, Somneuk Nilbunga, Sirinun Nilwarangoon, Ramida Watanapokasin
J Med Assoc Thai. 2015 Oct;98 Suppl 9:S91-7.
To determine the effects of alpha-mangostin on thioacetamide (TAA)-induced liver cirrhosis in rats.
Male Wistar rats were divided into 3 groups and treated with intraperitoneal injections of TAA (200 mg/kg) 3 times per week for per week for 8, 12 and 16 weeks, respectively. One subgroup was left untreated whereas the other two were treated either with 100 mg/kg α-mangostin or vehicle alone (80% DMSO, 20% water), which were administered intraperitoneally 3 times per weekfor a total of4 weeks. The incidence offibrotic nodules on the liver and the serum levels of the liver enzymes aspartate transaminase (AST) and alanine transaminase (ALT) were measured. Moreover the liver cirrhosis-related genes expression and p53 protein level in liver were analyzed by quantitative reverse transcription PCR and Western blot analysis, respectively.
Fibrotic nodules on the liver were formed upon treatment with TAA for 12 or 16 weeks. The nodules were then reduced by treatment with α-mangostin as compared to treatment with the vehicle DMSO. Moreover, the serum levels of the liver enzymes AST and ALT after treatment with α-mangostin decreased as compared to DMSO alone. The liver cirrhosis-related genes expression showed no significant differences, whereas the p53 protein level in liver showed that α-mangostin reduced risk of liver fibrosis through the decrease in p53 expression as compared to the TAA_DMSO treatment.
The results suggest that α-mangostin has a beneficial therapeutic effect in the TAA liver cirrhosis model. Further investigations on mechanisms of α-mangostin as therapeutic agent should be determined.
确定α-山竹素对硫代乙酰胺（TAA）诱导的大鼠肝硬化的影响。
将雄性Wistar大鼠分为3组，分别每周腹腔注射TAA（200mg/kg）3次，持续8周、12周和16周。一个亚组不进行处理，而另外两个亚组分别用100mg/kgα-山竹素或单独的溶媒（80%二甲基亚砜，20%水）处理，每周腹腔注射3次，共4周。测量肝脏纤维化结节的发生率以及肝酶天冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT）的血清水平。此外，分别通过定量逆转录PCR和蛋白质免疫印迹分析来检测肝脏中肝硬化相关基因的表达和p53蛋白水平。
用TAA处理12周或16周后肝脏形成纤维化结节。与用溶媒二甲基亚砜处理相比，用α-山竹素处理后结节减少。此外，与单独使用二甲基亚砜相比，用α-山竹素处理后肝酶AST和ALT的血清水平降低。肝硬化相关基因的表达没有显著差异，而肝脏中的p53蛋白水平显示，与TAA_二甲基亚砜处理相比，α-山竹素通过降低p53表达降低了肝纤维化风险。
结果表明α-山竹素在TAA肝硬化模型中具有有益的治疗作用。应进一步研究α-山竹素作为治疗剂的作用机制。
