Khunvirojpanich Montinee, Showpittaporchai Udomsri, Moongkamdi Primchanien, Pradidarcheep Wisuit
J Med Assoc Thai. 2015 Oct;98 Suppl 9:S53-60.
Ammonia metabolizing enzymes, carbamyol phosphate synthetase (CPS) and glutamine synthetase (GS), are expressed in the periportal and pericentral hepatocytes, respectively. CPS and GS function complementary to ensure complete ammonia detoxification. Immunohistochemical analysis confirmed the decline of both CPS and GS in cirrhotic rat liver induced by thioacetamide (TAA). Alpha-mangostin (AM), a major derivative of xanthone from mangosteen, has been reported to possess a wide range of pharmacological properties.
To examine the preventive effects of AM on CPS and GS expression in fibrotic and cirrhotic rats induced by TAA over sixteen weeks.
Twenty-four male Wistar rats were divided into 4 groups of 6 animals each. Group 1 was for control. Group 2 wasfor pure TAA treatment. Group 3 was for pure AM administration. Group 4, prevention group, was concurrently treated with TAA and AM. Immunohistochemical technique was employed in order to elucidate the expression of CPS and GS in each animal group.
Immunohistochemical staining for CPS and GS showed an increasing decline from week eight to sixteen under pure-TAA condition. Fibrous bridgings, nodule formations, and regenerative nodules were detected. Pure-AM condition yielded strongly CPS and GS-stained hepatocytes in afashion similar to the control. Results from the prevention group showed a decreasing decline of CPS and GS immuno-reactivity from week eight to sixteen as compared to pure-TAA condition. Fewer fibrous portal-caval bridgings were observed at week eight and CPS-positive hepatocytes were found in continuous rings.
Alpha-mangostin could partially preserve the normal expression of ammonia-metabolizing enzymes under TAA-induced fibrotic and cirrhotic conditions.
氨代谢酶，即氨基甲酰磷酸合成酶（CPS）和谷氨酰胺合成酶（GS），分别在肝门周围和肝中央周围的肝细胞中表达。CPS和GS发挥互补作用以确保氨的完全解毒。免疫组织化学分析证实硫代乙酰胺（TAA）诱导的肝硬化大鼠肝脏中CPS和GS均减少。α-山竹素（AM）是山竹果中氧杂蒽酮的主要衍生物，据报道具有广泛的药理特性。
研究AM对TAA诱导的纤维化和肝硬化大鼠16周内CPS和GS表达的预防作用。
24只雄性Wistar大鼠分为4组，每组6只。第1组为对照组。第2组接受单纯TAA治疗。第3组给予单纯AM给药。第4组为预防组，同时接受TAA和AM治疗。采用免疫组织化学技术以阐明各动物组中CPS和GS的表达。
在单纯TAA条件下，从第8周到第16周，CPS和GS的免疫组织化学染色显示下降趋势增加。检测到纤维桥接、结节形成和再生结节。单纯AM条件下产生的肝细胞CPS和GS染色强烈，其方式类似于对照组。预防组的结果显示，与单纯TAA条件相比，从第8周到第16周，CPS和GS免疫反应性的下降减少。在第8周观察到较少的纤维性门静脉-腔静脉桥接，并且发现CPS阳性肝细胞呈连续环状。
α-山竹素在TAA诱导的纤维化和肝硬化条件下可部分保留氨代谢酶的正常表达。
