肝脏缺血/再灌注（I/R）损伤是肝脏手术最常见的副作用之一。这种病理生理过程可能导致肝脏过度损伤。 Aloperine 是从苦豆子 (Sophora alopecuroides Linn) 中分离出来的活性成分，具有多种治疗作用，包括器官保护作用。然而，苦豆碱对肝缺血再灌注损伤的保肝作用尚未确定。 C57BL/6 小鼠被分配到假手术（sham）组、肝缺血/再灌注（I/R）组和苦豆碱（ALO）组。小鼠接受肝门闭塞 30 分钟。然后进行3小时的再灌注。假手术组的小鼠接受假手术。通过血浆天冬氨酸转氨酶（AST）和转氨酶丙氨酸转氨酶（ALT）水平、组织学评估、细胞凋亡、活化炎症细胞数量以及炎症细胞因子（包括肿瘤坏死因子-α（TNF-α））的表达水平来评估肝损伤。 α) 和白介素-6 (IL-6)。评估再灌注相关生存途径的蛋白质磷酸化状态。肝缺血再灌注损伤小鼠血浆 ALT 和 AST 水平升高、肝细胞凋亡增加、组织学结构异常和炎症反应升高。然而，苦豆素可改善缺血再灌注引起的肝损伤。此外，苦豆碱还能增强 I/R 后信号转导子和转录激活子 (STAT)-3 磷酸化的水平。 Ag490 是一种抑制 STAT-3 活性的药物，可消除阿洛佩林诱导的 STAT-3 磷酸化和肝脏保护作用。 Aloperine 通过 STAT-3 介导的保护机制改善肝缺血再灌注引起的肝损伤。肝缺血再灌注损伤患者可能会受益于阿洛品碱治疗。意义陈述 肝脏缺血/再灌注 (I/R) 可导致过度的肝脏损伤。这项研究表明，从苦豆子中分离出的活性成分苦豆碱在体内可改善肝缺血再灌注损伤和相关肝损伤，其潜在的保护机制可能涉及 STAT-3 信号通路。这些发现可能会导致临床实践中治疗肝缺血再灌注损伤的新方法的开发。版权所有 © 2024 美国药理学和实验治疗学会。

Hepatic ischemia/reperfusion (I/R) damage is one of the most common side effects of liver surgery. This pathophysiological process may lead to excessive hepatic damage. Aloperine is an active ingredient isolated from Sophora alopecuroides Linn and has a variety of therapeutic effects, including organ protection. However, the hepatoprotective effect of aloperine against hepatic I/R damage has not yet been determined. C57BL/6 mice were allocated to the sham-operated (sham), hepatic ischemia/reperfusion (I/R), and aloperine (ALO) groups. The mice were exposed to 30 min of hepatic hilum occlusion. Then a 3-hour reperfusion was performed. Mice in the sham group underwent sham surgery. Hepatic injury was evaluated by plasma aspartate aminotransferase (AST) and transaminase alanine aminotransferase (ALT) levels, histological evaluation, cell apoptosis, the number of activated inflammatory cells, and the expression levels of inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). The protein phosphorylation status of the reperfusion-associated survival pathways was evaluated. Mice with hepatic I/R injury presented increased plasma ALT and AST levels, increased hepatic apoptosis, abnormal histological structure, and elevated inflammatory responses. However, aloperine ameliorated hepatic I/R-induced injury. Moreover, aloperine enhanced the level of signal transducer and activator of transcription (STAT)-3 phosphorylation after I/R. Ag490, an agent that inhibits STAT-3 activity, abolished aloperine-induced STAT-3 phosphorylation and liver protection. Aloperine ameliorates hepatic I/R-induced liver injury via a STAT-3-mediated protective mechanism. Patients with hepatic I/R injury may benefit from aloperine treatment. Significance Statement Hepatic ischemia/reperfusion (I/R) can cause excessive liver damage. This study revealed that aloperine, an active component isolated from Sophora alopecuroides Linn., ameliorates hepatic I/R injury and related liver damage in vivo The underlying protective mechanism may involve the STAT-3 signaling pathway. These findings may lead to the development of a novel approach for treating hepatic I/R damage in clinical practice.Copyright © 2024 American Society for Pharmacology and Experimental Therapeutics.