Allowable warm ischemic time and morphological and biochemical changes in uterine ischemia/ reperfusion injury in cynomolgus macaque: a basic study for uterus transplantation
Allowable warm ischemic time and morphological and biochemical changes in uterine ischemia/ reperfusion injury in cynomolgus macaque: a basic study for uterus transplantation
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DOI：
10.1093/humrep/dex250
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发表时间：
2017-10-01
影响因子：
6.1
通讯作者：
Aoki, Daisuke
中科院分区：
文献类型：
--
作者：
Kisu, Iori;Umeneo, Kiyoko;Aoki, Daisuke
研究问题：食蟹猴子宫允许的热缺血时间是多长？子宫缺血/再灌注损伤会引起哪些形态和生化变化？总结答案：食蟹猴子宫热缺血可耐受长达4 h，子宫缺血不再引起进一步的形态和生化损伤后可再灌注 已知的情况：子宫移植是子宫因素不孕女性的一种潜在选择。人类和非人类灵长类动物允许的子宫热缺血时间和缺血/再灌注损伤尚不清楚。 研究设计、规模、持续时间：本实验研究包括 18 只具有周期性月经的雌性食蟹猴。 参与者/材料、环境、方法：将动物分为六组，每组三只猴子：对照组和子宫缺血组。 0.5, 1、2、4 和 8 小时。在血流阻断前、每次阻断时间后以及再灌注3小时后对子宫组织进行活检。每次阻断时间后以及再灌注5、15和30分钟后进行血液采样以测量生化数据。手术后监测月经恢复情况。评估缺血和再灌注后的形态、生理和生化变化。 主要结果和机会的作用：在热缺血4或8小时的所有动物中均观察到轻度肌肉变性和带状变性，但在热缺血4或8小时的动物中，缺血后立即和再灌注3小时后标本的外观没有显着差异。各组任意时间点生化参数均无显着变化。所有热缺血4小时以内的动物都恢复了定期月经，但子宫萎缩的热缺血8小时的动物都没有恢复。 研究问题：食蟹猴子宫允许的热缺血时间是多长？子宫缺血/再灌注损伤会引起哪些形态和生化变化？总结答案： 食蟹猴的子宫耐受时间长达 4 小时，子宫缺血后再灌注不会引起进一步的形态和生化变化。 已知信息：子宫移植是子宫因素不孕女性的潜在选择。人类和非人类灵长类动物允许的子宫热缺血时间和缺血/再灌注损伤尚不清楚。 研究设计、规模、持续时间：本实验研究包括 18 只具有周期性月经的雌性食蟹猴。 参与者/材料、环境、方法：将动物分为六组，每组三只猴子：对照组和子宫缺血组。 0.5, 1、2、4 和 8 小时。在血流阻断前、每次阻断时间后以及再灌注3小时后对子宫组织进行活检。每次阻断时间后以及再灌注5、15和30分钟后进行血液采样以测量生化数据。手术后监测月经恢复情况。评估缺血和再灌注后的形态、生理和生化变化。 主要结果和机会的作用：在热缺血4或8小时的所有动物中均观察到轻度肌肉变性和带状变性，但在热缺血4或8小时的动物中，缺血后立即和再灌注3小时后标本的外观没有显着差异。各组任意时间点生化参数均无显着变化。所有热缺血长达 4 小时的动物均恢复了定期月经，但子宫萎缩的热缺血 8 小时的动物并未恢复。 局限性和注意原因：本研究并未完全模拟实际移植中的热缺血，因为子宫未进行血管灌注、冷却、移植或重新吻合。非人类灵长类动物的结果不能总是外推到人类。研究结果的更广泛影响：研究结果表明，子宫中可耐受的热缺血时间预计将比其他重要器官的可耐受热缺血时间更长。
STUDY QUESTION: How long is the allowable warm ischemic time of the uterus and what morphological and biochemical changes are caused by uterine ischemia/reperfusion injury in cynomolgus macaques?SUMMARY ANSWER: Warm ischemia in the uterus of cynomolgus macaques is tolerated for up to 4 h and reperfusion after uterine ischemia caused no further morphological and biochemical changes.WHAT IS KNOWN ALREADY: Uterus transplantation is a potential option for women with uterine factor infertility. The allowable warm ischemic time and ischemia/reperfusion injury of the uterus in humans and non-human primates is unknown.STUDY DESIGN, SIZE, DURATION: This experimental study included 18 female cynomolgus macaques with periodic menstruation.PARTICIPANTS/MATERIALS, SETTING, METHODS: Animals were divided into six groups of three monkeys each: a control group and groups with uterine ischemia for 0.5, 1, 2, 4 and 8 h. Biopsies of uterine tissues were performed before blood flow blockage, after each blockage time, and after reperfusion for 3 h. Blood sampling was performed after each blockage time, and after reperfusion for 5, 15 and 30 min for measurement of biochemical data. Resumption of menstruation was monitored after the surgical procedure. Morphological, physiological and biochemical changes after ischemia and reperfusion were evaluated.MAIN RESULTS AND THE ROLE OF CHANCE: Mild muscle degeneration and zonal degeneration were observed in all animals subjected to warm ischemia for 4 or 8 h, but there were no marked differences in the appearance of specimens immediately after ischemia and after reperfusion for 3 h in animals subjected to 4 or 8 h of warm ischemia. There were no significant changes in any biochemical parameters at any time point in each group. Periodical menstruation resumed in all animals with warm ischemia up to 4 h, but did not recover in animals with warm ischemia for 8 h with atrophic uteri.STUDY QUESTION: How long is the allowable warm ischemic time of the uterus and what morphological and biochemical changes are caused by uterine ischemia/reperfusion injury in cynomolgus macaques?SUMMARY ANSWER: Warm ischemia in the uterus of cynomolgus macaques is tolerated for up to 4 h and reperfusion after uterine ischemia caused no further morphological and biochemical changes.WHAT IS KNOWN ALREADY: Uterus transplantation is a potential option for women with uterine factor infertility. The allowable warm ischemic time and ischemia/reperfusion injury of the uterus in humans and non-human primates is unknown.STUDY DESIGN, SIZE, DURATION: This experimental study included 18 female cynomolgus macaques with periodic menstruation.PARTICIPANTS/MATERIALS, SETTING, METHODS: Animals were divided into six groups of three monkeys each: a control group and groups with uterine ischemia for 0.5, 1, 2, 4 and 8 h. Biopsies of uterine tissues were performed before blood flow blockage, after each blockage time, and after reperfusion for 3 h. Blood sampling was performed after each blockage time, and after reperfusion for 5, 15 and 30 min for measurement of biochemical data. Resumption of menstruation was monitored after the surgical procedure. Morphological, physiological and biochemical changes after ischemia and reperfusion were evaluated.MAIN RESULTS AND THE ROLE OF CHANCE: Mild muscle degeneration and zonal degeneration were observed in all animals subjected to warm ischemia for 4 or 8 h, but there were no marked differences in the appearance of specimens immediately after ischemia and after reperfusion for 3 h in animals subjected to 4 or 8 h of warm ischemia. There were no significant changes in any biochemical parameters at any time point in each group. Periodical menstruation resumed in all animals with warm ischemia up to 4 h, but did not recover in animals with warm ischemia for 8 h with atrophic uteri.LIMITATIONS, REASON FOR CAUTION: Warm ischemia in actual transplantation was not exactly mimicked in this study because uteri were not perfused, cooled, transplanted or reanastomosed with vessels. Results in non-human primates cannot always be extrapolated to humans.WIDER IMPLICATIONS OF THE FINDINGS: The findings suggest that the tolerable warm ischemia time in the uterus is expected to be longer than that in other vital organs.