天津医药

天津医药 ›› 2017, Vol. 45 ›› Issue (6): 588-592.doi: 10.11958/20170174

• 实验研究 • 上一篇    下一篇

依达拉奉对不同冷缺血时间大鼠移植供肝 JAK2/STAT3 信号通路的影响

薛佩彤 1，张全胜 2，李欣 3，李宏 3△   

  1. 1 甘肃中医药大学（邮编 730030）；2 天津市器官移植重点实验室；3 武警后勤学院附属医院麻醉一科
  • 收稿日期:2017-02-13 修回日期:2017-05-01 出版日期:2017-06-15 发布日期:2017-07-05
  • 通讯作者: △通讯作者 E-mail：fch6161@sina.com E-mail:fch6161@sina.com
  • 作者简介:薛佩彤（1990），女，硕士在读，主要从事肝脏保护方面研究
  • 基金资助:
    武警医学院附属医院种子基金（FYM201102）

Effects of edaravone on JAK2/STAT3 signaling pathway in transplanted donor liver of rats with different cold ischemia times

XUE Pei-tong1, ZHANG Quan-sheng2, LI Xin3, LI Hong3△   

  1. 1 Gansu University of Chinese Medicine, Gansu 730030, China; 2 Tianjin Key Laboratory of Organ Transplantation; 3 Department of Anesthesiology, the Affiliated Hospital of Logistics College of the Chinese People’s Armed Police Force
  • Received:2017-02-13 Revised:2017-05-01 Published:2017-06-15 Online:2017-07-05
  • Contact: △Corresponding Author E-mail: fch6161@sina.com E-mail:fch6161@sina.com

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摘要： 目的 探讨依达拉奉对不同冷缺血时间大鼠移植供肝缺血再灌注损伤（IRI）后 JAK2/STAT3 信号通路的影 响。方法 SD 大鼠 102 只，随机分为假手术组、对照组及实验组。假手术组 6 只，游离肝脏，不进行移植；对照组及 实验组各 48 只，2 组各自按照不同冷缺血时间 30 min、6 h、12 h、18 h 分为 4 个处理亚组，每处理组供体、受体各 6 只。采用改良的“二袖套法”建立大鼠原位肝移植模型，供体采用腹主动脉灌注法，热缺血时间为 3～5 min。供肝在 不同冷缺血时间后，实验组分别于新肝血管开放前 5 min 经鼠尾静脉注射依达拉奉 3 mg/kg；对照组分别注射生理盐 水 3 mg/kg。各组受体均于 6 h 后处死取材。采用实时荧光定量 PCR（RT-PCR）检测受体供肝组织中 JAK2 和 STAT3 mRNA 的相对表达量。结果 内参基因 GAPDH 与检测基因 JAK2、STAT3 扩增良好；在同一冷缺血时间，与对 照组比较，实验组大鼠供肝基因 JAK2/STAT3 相对表达量均明显降低（P＜0.05）；随冷缺血时间延长，对照组 JAK2、 STAT3 mRNA 和实验组 STAT3 mRNA 相对表达量均呈逐渐降低趋势，而实验组 JAK2 mRNA 相对表达量呈先增后降 趋势（P＜0.05）。结论 依达拉奉对不同冷缺血时间移植供肝具有一定的保护作用。依达拉奉可延长供肝冷缺血时 间至 18 h，其机制可能与抑制肝细胞 JAK2/STAT3 信号转导通路有关。

关键词: 肝移植, 活体供者, 冷缺血, 再灌注损伤, 疾病模型, 动物, 大鼠, Sprague-Dawley, JAK2/STAT3, 依达拉奉

Abstract: Objective To investigate the effect of edaravone on the JAK2/STAT3 signaling pathway after ischemiareperfusion injury in donor rat liver under different cold ischemia times. Methods A total of 102 SD rats were randomly divided into sham operation group，control group and experimental group. Six rats were in sham operation group with free liver operation and no transplantation. Forty- eight rats were in control group and experimental group respectively, and divided into subgroups according to the different cold ischemia times (30 min, 6 h, 12 h and 18 h). There were 6 donors and 6 recipients in each group. The rat model of orthotopic liver transplantation was established by modified "two cuff method". All the donors were perfused by abdominal aorta and the warm ischemia time was 3-5 min. After different cold ischemia times, the experimental group was treated with edaravone (3 mg/kg) at 5 min before the opening of the new hepatic artery, and control group was injected with 3 mg/kg saline. Recipients of each group were sacrificed after 6 h. Finally, real-time fluorescence quantitative PCR was used to analyze the relative expression of JAK2/STAT3 mRNA of donor liver. Results The GAPDH gene and JAK2/STAT3 were well amplified. Under the same cold ischemia time, compared with the control group, the relative expression of JAK2/STAT3 was significantly decreased in the experimental group (P＜0.05). With the prolongation of cold ischemia time, the relative expressions of JAK2 and STAT3 mRNA showed a decreasing trend in control group and experimental group, while the relative expression of JAK2 mRNA increased first and then decreased in the experimental group (P＜0.05). Conclusion Edaravone has a protective effect on transplanted donor liver during different cold ischemia times, and extends the cold ischemia time for 18 h, which may be related to the inhibition of JAK2/STAT3 signal transduction pathway.

Key words: liver transplantation, living donors, cold ischemia, reperfusion injury, disease models, animal, rats, Sprague-Dawley, JAK2/STAT3, edaravone