FK506联合低温机械灌注保护大鼠供肝

基础医学与临床 ›› 2021, Vol. 41 ›› Issue (12): 1715-1718.

• 研究论文 • 下一篇

FK506联合低温机械灌注保护大鼠供肝

姜骊^1,2, 李建辉², 俞浩³, 李浩宇², 谢海洋², 周琳², 郑树森^2,3*

1.浙江大学医学院附属第一医院实验动物中心,浙江杭州 310003;
2.卫健委多器官联合移植研究重点实验室,浙江杭州 310003;
3.浙江大学医学院附属第一医院肝胆胰外科,浙江杭州 310003

收稿日期:2021-06-07 修回日期:2021-10-12 发布日期:2021-12-03
通讯作者: *shusenzheng@zju.edu.cn
基金资助:
国家自然科学基金(创新研究群体项目)(81721091);海南省重大科技计划(ZDKJ2019009);浙江省基础公益研究计划(LGF21H030006)

Protective effect of FK506 combined with hypothermic mechanical perfusion on donor liver of rats

JIANG Li^1,2, LI Jian-hui², YU Hao³, LI Hao-yu², XIE Hai-yang², ZHOU Lin², ZHENG Shu-sen^2,3*

1. Laboratory Animal Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003;
2. NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003;
3. Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China

Received:2021-06-07 Revised:2021-10-12 Published:2021-12-03
Contact: *shusenzheng@zju.edu.cn

摘要/Abstract

摘要： 目的探究他克莫司(FK506)联合低温机械灌注能否具有对大鼠肝脏移植缺血再灌注损伤的保护作用。方法将大鼠分为HTK液机械灌注(HTK)组和FK506+HTK液机械灌注(FK506+HTK)组,取出HTK液机械灌注组供体肝脏后,在4 ℃,150 mL HTK液状态下灌注3 h后进行原位肝移植,FK506+HTK组供肝在4 ℃,FK506+150 mL HTK液灌注3 h后进行原位肝移植,两组移植后3 和24 h取血,离心得血清,采用生化自动分析仪测定肝功能;移植后24 h麻醉取肝脏组织,甲醛固定进行HE染色,进行病理学观察。结果 FK506+HTK组ALT水平低于HTK组(P＜0.05),FK506+HTK组炎性因子浸润较HTK液组减少,肝细胞结构完整;FK506+HTK组炎性因子浸润较HTK液组减少,肝细胞结构完整。结论 FK506加入到灌注液中对供肝进行机械灌注,在移植后3 h内有效减少肝脏肝功能损伤和炎性损伤,对肝脏有一定的保护作用。

关键词: 低温机械灌注, FK506, 肝移植, 缺血/再灌注损伤

Abstract: Objective To investigate the protective effects of FK506 combined with low temperature mechanical perfusion on the reduction of ischemia reperfusion injury of rat liver transplants. Methods SD rats were divided into HTK group and FK506 + HTK group. Orthotopic liver transplantation was performed 3 hours after machine perfusion of 150 mL HTK (HTK group) or FK506+150 mL HTK (FK506 + HTK group). Blood samples were collected at 3 and 24 hours after transplantation in both groups, and serum samples were centrifuged for liver function test. Twenty-four hours after transplantation, liver tissues were collected and fixed with formalin for HE staining. Results Serum ALT levels in FK506+HTK group were significantly lower than that in HTK group (P＜0.05). Inflammatory infiltration in FK506+HTK group was less than that in the HTK group, and the liver structure was intact. Conclusions FK506 added into perfusate for machine perfusion of the donor liver can effectively reduce liver function damage and inflammation damage within 3 hours after transplantation, and has a certain protective effect on the liver.

Key words: hypothermic machine perfusion, FK506, liver transplantation, ischemia reperfusion injury

中图分类号:

R617

姜骊, 李建辉, 俞浩, 李浩宇, 谢海洋, 周琳, 郑树森. FK506联合低温机械灌注保护大鼠供肝[J]. 基础医学与临床, 2021, 41(12): 1715-1718.

JIANG Li, LI Jian-hui, YU Hao, LI Hao-yu, XIE Hai-yang, ZHOU Lin, ZHENG Shu-sen. Protective effect of FK506 combined with hypothermic mechanical perfusion on donor liver of rats[J]. Basic & Clinical Medicine, 2021, 41(12): 1715-1718.

参考文献

[1]中国器官移植发展报告(2015—2018)[M]. 黄洁夫. 北京:中国器官移植发展基金会, 2020:7-8.
[2]朱志军. 多途径扩展肝移植供肝来源[J]. 基础医学与临床, 2012, 32: 593-597.
[3]Nasralla D, Coussios CC, Mergental H, et al.A rando-mized trial of normothermic preservation in liver transplantation[J]. Nature, 2018, 557: 50-56.
[4]Thompson ER, Connelly C, Ali S, et al. Cell therapy during machine perfusion[J].Transpl Int, 2021, 34:49-58.
[5]Li J, Jia J, He N, et al. Combined kidney-liver perfusion enhances the proliferation effects of hypothermic perfusion on liver grafts via upregulation of IL-6/Stat3 signaling[J]. Mol Med Rep, 2019, 20:1663-1671.
[6]Ning H, Jia JJ, Xie HY, et al. Partial inhibition of HO-1 attenuates HMP-induced hepatic regeneration against liver injury in rats[J]. Oxid Med Cell Longev, 2018, 2018:1-11.
[7]O'Neill S, Srinivasa S, Callaghan CJ, et al. Novel organ perfusion and preservation strategies in transplantation-where are we going in the united kingdom?[J]. Transplantation, 2020,104:1813-1824.
[8]Sakr MF, Zetti GM, Hassanein TI, et al. FK 506 ameliorates the hepatic injury associated with ischemia and reperfusion in rats[J]. Hepatology (Baltimore, Md), 1991, 13: 947-951.
[9]Sasaki K, Miyake H, Kinoshita T, et al. Protective effect of FK506 and thromboxane synthase inhibitor on ischemia-reperfusion injury in non-heart-beating donor in rat orthotopic liver transplantation[J]. JMI, 2004, 51: 76-83.
[10]St Peter SD, Post DJ, Rodriguez-Davalos MI, et al. Tacrolimus as a liver flush solution to ameliorate the effects of ischemia/reperfusion injury following liver transplanta-tion[J].Liver Transpl, 2003, 9: 144-149.
[11]Pratschke S, Arnold H, Zollner A, et al. Results of the TOP study: prospectively randomized multicenter trial of an ex vivo tacrolimus rinse before transplantation in EDC livers[J]. Transplant Direct, 2016, 2: doi: 10.1097/TXD.0000000000000588.
[12]侯建存,李玉民,强喆,等. 缺血预处理对大鼠肝移植早期的保护作用[J]. 基础医学与临床, 2008,28:1317-1318.

FK506联合低温机械灌注保护大鼠供肝

Protective effect of FK506 combined with hypothermic mechanical perfusion on donor liver of rats

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