Lee H M, Jang H J, Kim S S, Kim H J, Lee S Y, Oh M Y, Kwan H C, Jang D S, Eom D W
Department of Anesthesia and Pain Medicine, Ulsan University, College of Medicine, Gangneung Asan Hospital, Gangneung, South Korea.
Department of Surgery, Ulsan University, College of Medicine, Gangneung Asan Hospital, Gangneung, South Korea.
Transplant Proc. 2016 May;48(4):1226-33. doi: 10.1016/j.transproceed.2016.01.024.
Eupatilin, a pharmacologically active flavone derived from Artemisia species, is known to have antioxidant and antiinflammatory activities. Ischemia-reperfusion injury (IRI) is a major critical event that commonly occurs after liver transplantation and resection. Furthermore, inflammatory responses to IRI exacerbate the resultant hepatic injury. In this study, we investigated whether eupatilin protects against IR-induced acute liver injury in mice.
Partial (70%) hepatic IRI was induced in male C57BL/6 mice by portal triad pedicle occlusion for 90 minutes followed by reperfusion for 6 hours. Eupatilin (10 mg/kg body weight, oral) was administered 4 days before the IRI.
Treatment with eupatilin significantly decreased serum alanine aminotransferase and serum aspartate aminotransferase as well as liver histologic changes. Eupatilin also prevented hepatic glutathione depletion and increased malondialdehyde levels induced by IRI. Western blotting indicated that eupatilin significantly increased the levels of heat shock protein and B-cell lymphoma 2 protein, attenuated inducible nitric oxide synthase, and cleaved caspase-3 levels 6 hours after IRI. The expression of the Toll-like receptor 2/4, and phosphorylated nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor was significantly decreased in the eupatilin pretreatment group.
Eupatilin improved the acute hepatic IRI by reducing inflammation and apoptosis. These findings suggest that eupatilin is a promising therapeutic agent against acute IR-induced hepatic damage.
灯盏乙素是一种从蒿属植物中提取的具有药理活性的黄酮，已知具有抗氧化和抗炎活性。缺血再灌注损伤（IRI）是肝移植和肝切除术后常见的主要关键事件。此外，对IRI的炎症反应会加剧由此导致的肝损伤。在本研究中，我们调查了灯盏乙素是否能保护小鼠免受IR诱导的急性肝损伤。
通过门静脉三联蒂阻断90分钟，然后再灌注6小时，在雄性C57BL/6小鼠中诱导部分（70%）肝脏IRI。在IRI前4天给予灯盏乙素（10mg/kg体重，口服）。
灯盏乙素治疗显著降低了血清丙氨酸氨基转移酶和血清天冬氨酸氨基转移酶以及肝脏组织学变化。灯盏乙素还可防止IRI诱导的肝脏谷胱甘肽耗竭并增加丙二醛水平。蛋白质印迹法表明，灯盏乙素显著增加了热休克蛋白和B细胞淋巴瘤2蛋白的水平，在IRI后6小时减弱了诱导型一氧化氮合酶和裂解的半胱天冬酶-3水平。在灯盏乙素预处理组中，Toll样受体2/4以及B细胞中κ轻链多肽基因增强子的磷酸化核因子抑制剂的表达显著降低。
灯盏乙素通过减轻炎症和细胞凋亡改善急性肝IRI。这些发现表明灯盏乙素是一种有前景的抗急性IR诱导肝损伤的治疗药物。
