Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Mol Immunol. 2018 Mar;95:83-90. doi: 10.1016/j.molimm.2018.01.015. Epub 2018 Feb 20.
Warm ischemia reperfusion injury (IRI) plays a key role in biliary complication, which is a substantial vulnerability of liver transplantation. The early pathophysiological changes of IRI are characterized by an excessive inflammatory response. S-Adenosylmethionine (SAM) is an important metabolic intermediate that modulates inflammatory reactions; however, its role in bile duct warm IRI is not known. In this study, male rats were treated with or without SAM (170 μmol/kg body weight) after orthotopic autologous liver transplantation. The histopathological observations showed that bile duct injury in the IRI group was more serious than in the SAM group. The alanine aminotransferase (ALT), alkaline phosphatase (ALP) and direct bilirubin (DBIL) levels in the serum of the IRI group were significantly increased compared to the SAM group (P < .05). Simultaneously, SAM effectively improved the survival of the transplant recipients. Furthermore, the HO and malondialdehyde (MDA) of the IRI group were much higher compared to the SAM group (P < .05). The GSH/GSSG ratio in the SAM group was significantly increased by SAM treatment compared to the IRI group (P < .05). SAM administration significantly inhibited macrophage infiltration in liver and bile duct tissues, down-regulated TNF-α levels and up-regulated IL-10 expression in bile duct tissues compared to the IRI group (P < .05). The number of apoptotic biliary epithelial cells and caspase-3-positive cells in IRI rat livers were much higher compared to those in SAM-treated rats at 24 h after liver transplantation (P < .05). These data suggested that SAM protected bile ducts against warm IRI by suppressing oxidative stress, inflammatory reactions and apoptosis of biliary epithelial cells after liver transplantation.α.
热缺血再灌注损伤（IRI）在胆系并发症中起关键作用，这是肝移植的一个显著弱点。IRI 的早期病理生理变化以过度炎症反应为特征。S-腺苷甲硫氨酸（SAM）是调节炎症反应的重要代谢中间产物；然而，其在胆管热 IRI 中的作用尚不清楚。在这项研究中，雄性大鼠在同种异体自体肝移植后用或不用 SAM（170 μmol/kg 体重）治疗。组织病理学观察表明，IRI 组胆管损伤比 SAM 组更严重。与 SAM 组相比，IRI 组血清丙氨酸氨基转移酶（ALT）、碱性磷酸酶（ALP）和直接胆红素（DBIL）水平显著升高（P<.05）。同时，SAM 有效提高了移植受者的存活率。此外，与 SAM 组相比，IRI 组的 HO 和丙二醛（MDA）水平要高得多（P<.05）。与 IRI 组相比，SAM 处理后 SAM 组的 GSH/GSSG 比值显著增加（P<.05）。与 IRI 组相比，SAM 给药显著抑制了肝和胆管组织中巨噬细胞的浸润，下调了胆管组织中 TNF-α水平，并上调了 IL-10 表达（P<.05）。与 SAM 治疗大鼠相比，IRI 大鼠肝脏中细胞凋亡的胆管上皮细胞和 caspase-3 阳性细胞的数量在肝移植后 24 小时明显更高（P<.05）。这些数据表明，SAM 通过抑制氧化应激、炎症反应和胆管上皮细胞凋亡来保护胆管免受热 IRI。
