Rodniem Siripa, Tiyao Vilailak, Nilbu-Nga Cheng, Poonkhum Raksawan, Pongmayteegul Sirinun, Pradidarcheep Wisuit
Department of Anatomy, Faculty of Medicine, Srinakharinwirot University, Bangkok, Thailand.
Histol Histopathol. 2019 Apr;34(4):419-430. doi: 10.14670/HH-18-052. Epub 2018 Oct 11.
Liver fibrosis is an excessive accumulation of scar tissue resulting from inflammation and cell death. Thioacetamide (TAA) is a well-known hepatotoxin that induces liver fibrosis. A marker of injured hepatocytes is transforming growth factor-beta 1 (TGF-β1), while alpha-smooth muscle actin (α-SMA) and tissue inhibitor of metalloproteinase 1 (TIMP-1) are markers of activated hepatic stellate cells. Alpha-mangostin, a major xanthone derivative from the mangosteen pericarp, has been shown to have anti-oxidant and anti-inflammatory activities. The objective of this study was to determine whether alpha-mangostin has a protective effect on TAA-induced liver fibrosis in rats. The rats were treated by intraperitoneal injection of compounds for eight weeks. For the control group a mixture of dimethyl sulfoxide and phosphate buffered saline was administered. Two hundred mg/kg BW of TAA was administered three times weekly. Alpha-mangostin was administered at 5 mg/kg BW and silymarin at 100 mg/kg BW, both twice weekly. TAA induced histologically recognizable liver damage and fibrosis, as anticipated. Furthermore, it increased immunohistochemically detectable TGF-β1, α-SMA and TIMP-1. Co-administration of alpha-mangostin or silymarin with TAA prevented or ameliorated the effects of TAA administration alone. The anti-fibrotic effect of alpha-mangostin was stronger than that of silymarin.
肝纤维化是由炎症和细胞死亡导致的瘢痕组织过度积累。硫代乙酰胺（TAA）是一种众所周知的可诱导肝纤维化的肝毒素。转化生长因子-β1（TGF-β1）是受损肝细胞的标志物，而α-平滑肌肌动蛋白（α-SMA）和金属蛋白酶组织抑制剂1（TIMP-1）是活化肝星状细胞的标志物。α-山竹黄酮是山竹果皮中的一种主要氧杂蒽酮衍生物，已被证明具有抗氧化和抗炎活性。本研究的目的是确定α-山竹黄酮对TAA诱导的大鼠肝纤维化是否具有保护作用。通过腹腔注射化合物对大鼠进行治疗，持续八周。对照组给予二甲亚砜和磷酸盐缓冲盐水的混合物。每周三次给予200mg/kg体重的TAA。α-山竹黄酮以5mg/kg体重给药，水飞蓟素以100mg/kg体重给药，均为每周两次。正如预期的那样，TAA诱导了组织学上可识别的肝损伤和纤维化。此外，它还增加了免疫组织化学可检测到的TGF-β1、α-SMA和TIMP-1。α-山竹黄酮或水飞蓟素与TAA联合给药可预防或改善单独给予TAA的效果。α-山竹黄酮的抗纤维化作用比水飞蓟素更强。
