Liu Jia, Xiao Jiansheng, Deng Qin, Fu ZhiHui, Xiao Qi
Department of Transplantation, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
Ann Transplant. 2024 Jul 16;29:e944153. doi: 10.12659/AOT.944153.
BACKGROUND Ginkgetin inhibits growth of tumor cells, reducing blood lipids, and improving atherosclerosis, but the protective effect of ginkgetin in donation after cardiac death (DCD) livers is still unknown. The aim of this study was to determine whether pretreatment of DCD donor livers with ginkgetin can reduce inflammatory response through the JAK2/STAT3 signaling pathway. MATERIAL AND METHODS Twenty male Sprague-Dawley rats (200-250 g) were randomly divided into 4 groups: Sham, DCD, Ginkgetin (0.6 mg/kg) pretreatment 1 h before surgery, and Ginkgetin (0.6 mg/kg) plus broussonin E (0.3 mg/kg) (JAK2/STAT3 signaling agonist) pretreatment 1 h before surgery. Rat livers were subjected to 30 min warm ischemia and 24 h cold storage to simulate the preservation process of DCD donor livers, followed by normothermic machine perfusion for 1 h to simulate liver reperfusion in vivo. Liver tissues and perfusate samples were collected for further studies. RESULTS Ginkgetin pretreatment significantly decreased the values of ALT and AST (P<0.05), and improved histological alterations according to improved Suzuki's Score (P<0.05). Ginkgetin also inhibited the protein expression levels of p-JAK2/JAK2 and p-STAT3/STAT3 (P<0.05). Furthermore, ginkgetin pretreatment inhibited levels of interleukin-1β, interleukin-6 and tumor necrosis factor a (P<0.05) to suppress inflammatory response. In addition, broussonin E reversed the improvement of ginkgetin on DCD donor livers. CONCLUSIONS Ginkgetin can inhibit the inflammatory response through the JAK2/STAT3 signaling pathway to improve the quality of DCD donor livers.
背景 白果素可抑制肿瘤细胞生长、降低血脂并改善动脉粥样硬化，但白果素对心脏死亡后供肝（DCD）的保护作用尚不清楚。本研究旨在确定白果素预处理DCD供肝是否能通过JAK2/STAT3信号通路减轻炎症反应。 材料与方法 将20只雄性Sprague-Dawley大鼠（200-250 g）随机分为4组：假手术组、DCD组、术前1小时白果素（0.6 mg/kg）预处理组和术前1小时白果素（0.6 mg/kg）加布鲁松宁E（0.3 mg/kg）（JAK2/STAT3信号激动剂）预处理组。对大鼠肝脏进行30分钟热缺血和24小时冷保存以模拟DCD供肝的保存过程，随后进行1小时常温机器灌注以模拟体内肝脏再灌注。收集肝组织和灌注液样本进行进一步研究。 结果 白果素预处理显著降低了ALT和AST值（P<0.05），并根据改良的铃木评分改善了组织学改变（P<0.05）。白果素还抑制了p-JAK2/JAK2和p-STAT3/STAT3的蛋白表达水平（P<0.05）。此外，白果素预处理抑制了白细胞介素-1β、白细胞介素-6和肿瘤坏死因子α的水平（P<0.05）以减轻炎症反应。此外，布鲁松宁E逆转了白果素对DCD供肝的改善作用。 结论 白果素可通过JAK2/STAT3信号通路抑制炎症反应，从而改善DCD供肝的质量。
