Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, China; Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China; Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of the People's Republic of China, Beijing 100191, China; Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People's Republic of China, Beijing 100191, China; Beijing Microvascular Institute of Integration of Chinese and Western Medicine, Beijing 100191, China; State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin 300499, China.
Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China; Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of the People's Republic of China, Beijing 100191, China; Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People's Republic of China, Beijing 100191, China; Beijing Microvascular Institute of Integration of Chinese and Western Medicine, Beijing 100191, China; State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin 300499, China.
Free Radic Biol Med. 2018 Dec;129:202-214. doi: 10.1016/j.freeradbiomed.2018.09.009. Epub 2018 Sep 13.
The transplanted liver inevitably suffers from ischemia reperfusion (I/R) injury, which represents a key issue in clinical transplantation determining early outcome and long-term graft survival. A solution is needed to deal with this insult. This study was undertaken to explore the effect of Caffeic acid (CA), a naturally occurring antioxidant, on I/R injury of grafted liver and the mechanisms involved. Male Sprague-Dawley rats underwent orthotopic liver transplantation (LT) in the absence or presence of CA administration. In vitro, HL7702 cells were subjected to hypoxia/reoxygenation. LT led to apparent hepatic I/R injury, manifested by deteriorated liver function, microcirculatory disturbance and increased apoptosis, along with increased PDIA3 expression and nicotinamide adenosine dinucleotide phosphate (NADPH) oxidase activity, and membrane translocation of NADPH oxidase subunits. Treatment with CA attenuated the above alterations. siRNA/shRNA-mediated knockdown of PDIA3 in HL7702 cells and rats played the same role as CA not only in inhibiting ROS production and NADPH oxidase activity, but also in alleviating hepatocytes injury. CA protects transplanted livers from injury, which is likely attributed to its protection of oxidative damage by interfering in PDIA3-dependent activation of NADPH oxidase.
移植肝脏不可避免地会遭受缺血再灌注（I/R）损伤，这是决定临床移植早期结果和长期移植物存活的关键问题。需要一种解决方案来应对这种损伤。本研究旨在探讨咖啡酸（CA）作为一种天然抗氧化剂对移植肝脏 I/R 损伤的作用及其机制。雄性 Sprague-Dawley 大鼠在不存在或存在 CA 给药的情况下进行原位肝移植（LT）。在体外，HL7702 细胞经历缺氧/复氧。LT 导致明显的肝 I/R 损伤，表现为肝功能恶化、微循环障碍和细胞凋亡增加，同时 PDIA3 表达和烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶活性增加，NADPH 氧化酶亚基发生膜易位。CA 处理可减轻上述改变。HL7702 细胞和大鼠的 siRNA/shRNA 介导的 PDIA3 敲低与 CA 一样，不仅抑制 ROS 产生和 NADPH 氧化酶活性，而且减轻肝细胞损伤。CA 可保护移植肝脏免受损伤，这可能归因于其通过干扰 PDIA3 依赖性 NADPH 氧化酶激活来保护氧化损伤。
