基础研究(Basic Research)

他莫昔芬对腹主动脉瘤的治疗作用及其疗效性别差异的实验研究

Published at: 2016年第25卷第12期

高甫 1 , 焦洋 1 , 张小明 1 , 李伟 1
1 北京大学人民医院 血管外科,北京 100044
通讯作者 伟 李 Email: mailtowei@qq.com
DOI: 10.3978/j.issn.1005-6947.10.3978/j.issn.1005-6947.2016.12.010
基金:
国家自然科学基金资助项目 81470574
北京大学人民医院研究与发展基金资助项目 2118000537

摘要

目的:探讨他莫昔芬对小鼠腹主动脉瘤(AAA)的治疗作用及疗效的性别差异。方法:选择老年(60周龄)野生型C57BL/6小鼠,分3批进行实验,分别行单纯AAA造模(弹力蛋白酶诱导)、他莫昔芬预防性给药+AAA造模、AAA造模+他莫昔芬治疗;各批实验中的小鼠均雌雄各半,并设假手术对照,均于术后14 d取腹主动脉标本行相关指标检测。结果:第1批实验中雌雄鼠的AAA发生率均为100%。第2批实验中,雌鼠AAA的发生率明显低于雄鼠(30% vs. 80%,P<0.05);血管的病理学改变明显轻于雄鼠,且雌鼠血管组织中雌激素受体α、过氧化氢酶水平明显高于雄鼠,而PCNA水平及炎症细胞及炎症因子水平明显低于雄鼠(均P<0.05)。第3批实验中,雌鼠AAA的发生率明显低于雄鼠(50% vs. 100%,P<0.05);且雌鼠血管组织的病理改变、增殖反应、炎症反应均轻于雄鼠(均P<0.05)。结论:他莫昔芬对AAA的发生、发展方面有明显的抑制作用,但其作用有性别差异,表现为对雌鼠的AAA有较好的预防及治疗作用,对雄鼠有一定的预防作用而无治疗作用,机制可能与其对雌性动物有较强的雌激素受体诱导作用有关。


Therapeutic effect of tamoxifen on abdominal aortic aneurysm and gender difference in its efficacy: an experimental study

Abstract

Objective: To investigate the therapeutic effect of tamoxifen on abdominal aortic aneurysm (AAA) and gender difference in its efficacy in mice. Methods: Aged C57BL/6 mice (60-week old) were used to conduct experiment in 3 batches, in which, the mice underwent AAA model creation (induced by elastase) alone, prophylactic tamoxifen administration plus AAA model creation or AAA model creation followed by tamoxifen treatment, respectively. In each batch of experiment, half of the mice were male and half were female, and sham operation controls were used, and the specimens of abdominal aorta in all mice were harvested on postoperative day 14 for observing the relevant parameters. Results: In the first batch of experiment, the AAA formation rate was 100% in either male or female mice. In the second batch of experiment, the AAA formation rate in female mice was significantly lower than that in male mice (30% vs. 80%, P<0.05), and pathologic changes were remarkably milder, the levels of estrogen receptor α and catalase were significantly higher, while the levels of PCNA, inflammatory cells and cytokines were significantly lower in vascular tissues of female mice than those in vascular tissues of male mice (all P<0.05). In the third batch of experiment, the AAA formation rate in female mice was significantly lower than that in male mice (50% vs. 100%, P<0.05), with the milder pathologic changes, proliferative responses and inflammatory responses in vascular tissues of female mice than those in vascular tissues of male mice (all P<0.05). Conclusion: Tamoxifen has significant inhibitory effect on the occurrence and development of AAA. However, its action has gender difference which shows better preventive and therapeutic effect in female mice, and relative preventive effect but little therapeutic effect in male mice, and the mechanism may probably be associated with its strong estrogen receptor induction in female animals.


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引用

引用本文: 甫 高, 洋 焦, 小明 张, 伟 李. 他莫昔芬对腹主动脉瘤的治疗作用及其疗效性别差异的实验研究[J]. 中国普通外科杂志, 2016, 25(12): 1725-1731.
Cite this article as: GAO Fu, JIAO Yang, ZHANG Xiaoming, LI Wei . Therapeutic effect of tamoxifen on abdominal aortic aneurysm and gender difference in its efficacy: an experimental study [J]. Chin J Gen Surg, 2016, 25(12): 1725-1731.