人离体子宫冷灌注及冷缺血保存的安全区间

doi:10.6040/j.issn.1671-7554.0.2016.575

山东大学学报（医学版） ›› 2017, Vol. 55 ›› Issue (1): 85-91.doi: 10.6040/j.issn.1671-7554.0.2016.575

人离体子宫冷灌注及冷缺血保存的安全区间

许鑫鑫¹,刘雯¹,万吉鹏²,李涛²,王飞²,王霞³,颜磊¹,李长忠²,陈子江¹

1. 山东大学附属生殖医院国家辅助生殖与优生工程技术研究中心生殖内分泌教育部重点实验室(山东大学)山东省生殖医学重点实验室, 山东济南 250001;2.山东大学附属省立医院妇科, 山东济南 250021;3. 山东大学医学院生理学研究所, 山东济南 250012

收稿日期:2016-05-19 出版日期:2017-01-10 发布日期:2017-01-10
通讯作者: 颜磊. E-mail:yanleiandu@163.com 李长忠. E-mail:15168888909@163.com E-mail:yanleiandu@163.com
基金资助:
国家自然科学基金(81571414)

Safety limit of cold extracorporeal perfusion and ischaemic storage of human uterus

XU Xinxin¹, LIU Wen¹, WAN Jipeng², LI Tao², WANG Fei², WANG Xia³, YAN Lei¹, LI Changzhong², CHEN Zijiang¹

1. Center for Reproductive Medicine, Shandong University;
National Research Center for Assisted Reproductive Technology and Reproductive Genetics;
Key Laboratory of Reproductive Endocrinology(Shandong University), Ministry of Education;
Shandong Provincial Key Laboratory of Reproductive Medicine, Jinan 250001, Shandong, China;
2. Department of Gynecology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, China;
3. Institute of Physiology, School of Medicine, Shandong University, Jinan 250012, Shandong, China

Received:2016-05-19 Online:2017-01-10 Published:2017-01-10

摘要/Abstract

摘要： 目的探讨人离体子宫组氨酸-色氨酸-酮戊二酸盐(HTK)液冷灌注及冷缺血保存的安全区间。方法取因宫颈癌行广泛子宫切除术的患者子宫7例,3例于低温条件下用HTK液经子宫动脉灌注,测定一定灌注压力所对应的灌注高度,建立灌注高度与灌注压之间关系的数学模型;4例在适当灌注高度下短时灌注后取子宫内膜及肌组织于HTK保存液和生理盐水中保存,两组又根据保存时间(0、3、6、24 h)的不同分为0 h组、HTK 3 h组、HTK 6 h组、HTK 24 h组、生理盐水3 h组、生理盐水6 h组和生理盐水24 h组,测定不同保存时限的子宫组织细胞形态及平滑肌收缩能力,分析离体子宫灌注后冷缺血最佳保存时限。结果灌注压90~140 mmHg对应的灌注高度为62~122 cm;与0 h组比较,HTK3 h组和HTK6 h组的子宫标本在光镜及电镜下形态学结构均未见明显改变,但HTK 24 h组及所有的生理盐水保存组的样本均出现不同程度的细胞水肿、细胞间失去联系、线粒体肿胀及染色质粗染等不可逆的退化性改变;HTK 3 h、HTK 6 h和HTK 24 h组的3组标本的肌收缩力差异均无统计学意义(P=0.772);而与相同时段HTK组标本相比,生理盐水3 h、6 h和24 h组标本的肌收缩最大波幅均明显降低(P<0.05)。结论人类离体子宫组织低温HTK液安全灌注高度是62~122 cm,短时灌注后4 ℃ HTK液保存状态下可耐受冷缺血至少6 h。

关键词: 离体灌注, 器官保存, HTK保存液, 子宫移植, 冷缺血保存

Abstract: Objective To investigate the safety limit of cold extracorporeal perfusion with histidine-tryptophane-ketoglutarate(HTK)and ischaemic storage of human uterus. Methods A total of 7 uteri were obtained from patients undergoing extensive hysterectomy for cervical carcinoma. Three of them were perfused with cold HTK solution through each artery to detect the safe height of perfusion and to establish the mathematical model showing the relation between perfusion height and pressure. The other four uteri were perused at proper height, and then endometrium and myometrial tissues were collected and stored in HTK or normal saline(NS). The samples were then divided into 0 h group, HTK 3 h 山东大学学报 (医学版)55卷1期 -许鑫鑫,等.人离体子宫冷灌注及冷缺血保存的安全区间 \=-group, HTK 6 h group, HTK 24 h group, NS 3 h group, NS 6 h group and NS 24 h group. The cellular morphology and contractility of each group was detected, and the tolerability of human uterine tissue to cold ischaemic after short-time perfusion was determined. Results The corresponding perfusion height of 90-140 mmHg perfusion pressure was 62-122 cm. Compared with 0 h group, the HTK 3 h and HTK 6 h groups did not exhibit any major changes, while the HTK 24 h group and NS groups displayed degenerative changes such as hydropic changes, loss of intercellular contacts, hydropic mitochondria and coarse chromatin. No apparent difference in contractility was observed in specimens in HTK 3 h, HTK 6 h and HTK 24 h groups(P=0.772), but the contractility weakened significantly in the NS groups compared with the HTK groups(P<0.05). Conclusion The safe height is 62-122 cm for extracorporeal perfusion of human uterus by cold HTK solution; human uterine myometrial tissue can tolerate cold ischaemia for at least 6 h when stored in HTK solution after short-time extracorporeal perfusion.

Key words: Extracorporeal perfusion, HTK solution, Human uterine transplantation, Cold ischaemic storage, Organ preservation

中图分类号:

R617

许鑫鑫,刘雯,万吉鹏,李涛,王飞,王霞,颜磊,李长忠,陈子江. 人离体子宫冷灌注及冷缺血保存的安全区间[J]. 山东大学学报（医学版）, 2017, 55(1): 85-91.

XU Xinxin, LIU Wen, WAN Jipeng, LI Tao, WANG Fei, WANG Xia, YAN Lei, LI Changzhong, CHEN Zijiang. Safety limit of cold extracorporeal perfusion and ischaemic storage of human uterus[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(1): 85-91.

参考文献

[1] Brannstrom M, Diaz-Garcia C, Hanafy A, et al. Uterus transplantation: animal research and human possibilities[J]. Fertil Steril, 2012, 97(6):1269-1276.
[2] Johannesson L, Jarvholm S. Uterus transplantation: current progress and future prospects[J]. Int J Womens Health, 2016, 8:43-51. doi:10.2147/IJWH.S75635. eCollection, 2016.
[3] Racho El-Akouri R, Kurlberg G, Brannstrom M. Successful uterine transplantation in the mouse: pregnancy and post-natal development of offspring[J]. Hum Reprod, 2003, 18(10):2018-2023.
[4] Wranning CA, Akhi SN, Diaz-Garcia C, et al. Pregnancy after syngeneic uterus transplantation and spontaneous mating in the rat[J]. Hum Reprod, 2011, 26(3):553-558.
[5] Wranning CA, Dahm-Kahler P, Molne J, et al. Transplantation of the uterus in the sheep: oxidative stress and reperfusion injury after short-time cold storage[J]. Fertil Steril, 2008, 90(3):817-826.
[6] 沈芸,王增涛,陈子江,等. Beagle犬自体子宫卵巢移植动物模型的构建[J]. 中华显微外科杂志,2006,29(6): 450-452.
[7] Mihara M, Kisu I, Hara H, et al. Uterine autotransplantation in cynomolgus macaques: the first case of pregnancy and delivery[J]. Hum Reprod, 2012, 27(8):2332-2340.
[8] Brännström M, Johannesson L, Bokström H, et al. Livebirth after uterus transplantation[J]. Lancet, 2015, 385(9968):607-616.
[9] Obara H, Kisu I, Kato Y, et al. Surgical technique for allogeneic uterus transplantation in macaques[J]. Sci Rep, 2016, 6:35989. doi:10.1038/srep35989.
[10] Johannesson L, Enskog A, Dahm-Kahler P, et al. Uterus transplantation in a non-human primate: long-term follow-up after autologous transplantation[J]. Hum Reprod, 2012, 27(6):1640-1648.
[11] 李金东, 王安彪, 张海洲, 等. 肺动脉灌注HTK液对肺动脉高压先心病患儿术后的肺保护作用[J]. 山东大学学报(医学版), 2010, 48(6):88-91. LI Jindong, WANG Anbiao, ZHANG Haizhou, et al. Effect of pulmonary artery perfusion with HTK solution on congenital heart disease patients with pulmonary hypertension[J]. Journal of Shandong University(Health Sciences), 2010, 48(6):88-91.
[12] Brannstrom M, Johannesson L, Dahm-Kahler P, et al. First clinical uterus transplantation trial: a six-month report[J]. Fertil Steril, 2014, 101(5):1228-1236.
[13] Wei L, Xue T, Yang H, et al. Modified uterine allotransplantation and immunosuppression procedure in the sheep model[J]. PLoS One, 2013, 8(11):e81300. doi:10.1371/journal.pone.0081300.
[14] Fayed NA, Sayed EI, Saleh SM, et al. Effect of dexmedetomidine on hepatic ischemia-reperfusion injury in the setting of adult living donor liver transplantation[J]. Clin Transplant, 2016, 30(4):470-482.
[15] Johannesson L, Enskog A, Molne J, et al. Preclinical report on allogeneic uterus transplantation in non-human primates[J]. Hum Reprod, 2013, 28(1):189-198.
[16] Gauthier T, Bertin F, Fourcade L, et al. Uterine allotransplantation in ewes using an aortocava patch[J]. Hum Reprod, 2011, 26(11):3028-3036.
[17] Akar ME, Erdogan O. Uterus transplantation[J]. Fertil Steril, 2013, 100(5):e34. doi: 10.1016/j.fertnstert.2013.08.047.
[18] Wranning CA, Molne J, El-Akouri RR, et al. Short-term ischaemic storage of human uterine myometrium-basic studies towards uterine transplantation[J]. Hum Reprod, 2005, 20(10):2736-2744.
[19] 吕晓刚, 王沂峰, 陈高文, 等. 人类子宫组织耐受冷缺血损伤时限的探讨[J]. 器官移植, 2014, 5(1):4-7. L(¨overU)Xiaogang, WANG Yifeng, CHEN Gaowen, et al. Limit of human uterine tissue tolerating cold ischemic injury[J]. Organ Transplantation, 2014, 5(1):4-7.
[20] Li Y, Guo S, Liu G, et al. Three preservation solutions for cold storage of heart allografts: a systematic review and meta-analysis[J]. Artif Organs, 2016, 40(5):489-496.
[21] Adam R, Delvart V, Karam V, et al. Compared efficacy of preservation solutions in liver transplantation: a long-term graft outcome study from the European Liver Transplant Registry[J]. Am J Transplant, 2015, 15(2):395-406.
[22] Kisu I, Mihara M, Banno K, et al. Risks for donors in uterus transplantation[J]. Reprod Sci, 2013, 20(12):1406-1415.

多维度评价

Viewed

Full text

Abstract

Cited

Shared

Discussed

人离体子宫冷灌注及冷缺血保存的安全区间

Safety limit of cold extracorporeal perfusion and ischaemic storage of human uterus

PDF (PC)

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 3

多维度评价

本文评价

推荐阅读 0

[1]	王小平，张瑞斌，朱彬，高庆贞，靖永胜，任万军，王璞，王琪. MHC-Ⅰ细胞内抗体重组腺相关病毒载体的构建[J]. 山东大学学报(医学版), 2012, 50(12): 37-.
[2]	杨德君，张海斌，司马辉，朱楠，杨广顺 . 肝移植后胆道并发症早期肝功能的变化[J]. 山东大学学报(医学版), 2010, 48(10): 98-100.
[3]	刘仰东，李香铁，刘少鸽，石岩，杨先振. 腹腔镜辅助小切口亲属活体供肾切除术[J]. 山东大学学报(医学版), 2010, 48(10): 108-110.