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大鼠子宫的实验性静态冷藏:补充松弛素或促红细胞生成素的HTK-N溶液的保护作用

Experimental Static Cold Storage of the Rat Uterus: Protective Effects of Relaxin- or Erythropoietin-Supplemented HTK-N Solutions.

作者信息

Jakubauskiene Lina, Jakubauskas Matas, Razanskiene Gintare, Leber Bettina, Ramasauskaite Diana, Strupas Kestutis, Stiegler Philipp, Schemmer Peter

机构信息

General, Visceral and Transplant Surgery, Department of Surgery, Medical University of Graz, Auenbruggerplatz 2, 8036 Graz, Austria.

Faculty of Medicine, Vilnius University, M. K. Ciurlionio Street 21, 03101 Vilnius, Lithuania.

出版信息

Biomedicines. 2022 Oct 28;10(11):2730. doi: 10.3390/biomedicines10112730.

DOI:10.3390/biomedicines10112730
PMID:36359252
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9687853/
Abstract

Uterus transplantation (UTx) is the only treatment method for women with absolute uterine infertility. Currently, the number of grafts retrieved from deceased donors is increasing; hence, prolonged cold ischemia time is inevitable. Thus, this study was designed to assess the effect of the novel relaxin (RLN)- or erythropoietin (EPO)-supplemented Custodiol-N (HTK-N) solutions in an experimental uterus static cold storage (SCS) model. A total of 15 Sprague Dawley rats were used. Uterus horns were randomly assigned into three groups ( = 10/group). SCS was performed by keeping samples at 4 °C in HTK-N solution without or with different additives: 10 IU/mL EPO or 20 nM RLN. Tissue samples were taken after 8 and 24 h of preservation. Uterine tissue histology, and biochemical and immunohistochemical markers were analyzed. No significant differences in SCS-induced tissue damage were observed between groups after 8 h of preservation. Uterine tissue histology, MDA, SOD levels and the TUNEL-positive cell number showed severe damage in HTK-N without additives after 24 h of preservation. This damage was significantly attenuated by adding RLN to the preservation solution. EPO showed no favorable effect. Our study shows that RLN as an additive to an HTK-N solution can serve as an effective uterine tissue preservative in the uterus SCS setting.

摘要

子宫移植(UTx)是治疗绝对子宫性不孕女性的唯一方法。目前,从已故供体获取的移植物数量在增加,因此,延长的冷缺血时间不可避免。因此,本研究旨在评估新型补充松弛素(RLN)或促红细胞生成素(EPO)的Custodiol-N(HTK-N)溶液在实验性子宫静态冷藏(SCS)模型中的效果。总共使用了15只Sprague Dawley大鼠。子宫角随机分为三组(每组n = 10)。通过将样本置于4℃的无添加剂或添加不同添加剂的HTK-N溶液中进行SCS:10 IU/mL EPO或20 nM RLN。保存8小时和24小时后采集组织样本。分析子宫组织组织学、生化和免疫组化标志物。保存8小时后,各组之间未观察到SCS诱导的组织损伤有显著差异。保存24小时后,无添加剂的HTK-N溶液中的子宫组织组织学、丙二醛(MDA)、超氧化物歧化酶(SOD)水平和TUNEL阳性细胞数显示出严重损伤。通过在保存溶液中添加RLN,这种损伤得到显著减轻。EPO未显示出有利作用。我们的研究表明,在子宫SCS环境中,RLN作为HTK-N溶液的添加剂可作为一种有效的子宫组织防腐剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcdb/9687853/f73cbc460982/biomedicines-10-02730-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcdb/9687853/9a44eac0872d/biomedicines-10-02730-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcdb/9687853/f73cbc460982/biomedicines-10-02730-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcdb/9687853/9a44eac0872d/biomedicines-10-02730-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcdb/9687853/f73cbc460982/biomedicines-10-02730-g002.jpg

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本文引用的文献

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Int J Mol Sci. 2021 Oct 22;22(21):11417. doi: 10.3390/ijms222111417.
2
Custodiol-N Is Superior to Custodiol Solution in Experimental Rat Uterus Preservation.Custodiol-N 在实验大鼠子宫保存中优于 Custodiol 溶液。
Int J Mol Sci. 2020 Oct 28;21(21):8015. doi: 10.3390/ijms21218015.
3
First birth from a deceased donor uterus in the United States: from severe graft rejection to successful cesarean delivery.
美国首例已故供者子宫内孕育活产:从严重移植排斥到成功剖宫产分娩。
Am J Obstet Gynecol. 2020 Aug;223(2):143-151. doi: 10.1016/j.ajog.2020.03.001. Epub 2020 Mar 7.
4
Relaxin Positively Influences Ischemia-Reperfusion Injury in Solid Organ Transplantation: A Comprehensive Review.松弛素对实体器官移植中缺血再灌注损伤的影响:全面综述。
Int J Mol Sci. 2020 Jan 17;21(2):631. doi: 10.3390/ijms21020631.
5
A prospective, randomized, single-blind, multicentre, phase III study on organ preservation with Custodiol-N solution compared with Custodiol® solution in organ transplantation (kidney, liver and pancreas).一项关于使用 Custodiol-N 溶液与 Custodiol®溶液进行器官保存的前瞻性、随机、单盲、多中心、III 期研究,用于器官移植(肾、肝和胰腺)。
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Tissue conservation for transplantation.用于移植的组织保存。
Innov Surg Sci. 2017 Aug 8;2(4):171-187. doi: 10.1515/iss-2017-0010. eCollection 2017 Dec.
7
Metabolic alterations of uterine grafts after extended cold ischemic storage: experimental study in ewes.子宫移植物在延长冷缺血储存后的代谢改变:绵羊的实验研究。
Mol Hum Reprod. 2019 Oct 28;25(10):647-659. doi: 10.1093/molehr/gaz041.
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Live versus deceased donor in uterus transplantation.活体与死亡供体在子宫移植中的比较。
Fertil Steril. 2019 Jul;112(1):24-27. doi: 10.1016/j.fertnstert.2019.05.029.
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Changes in the metabolic composition of storage solution with prolonged cold ischemia of the uterus.子宫长时间冷缺血时储存液代谢成分的变化。
J Assist Reprod Genet. 2019 Jun;36(6):1169-1178. doi: 10.1007/s10815-019-01477-y. Epub 2019 May 12.
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