米非司酮对Wistar大鼠窗口期子宫内膜整合素和血管内皮生长因子基因表达的影响

doi:10.3969/j.issn.1674-5817.2017.05.011

实验动物与比较医学 ›› 2017, Vol. 37 ›› Issue (5): 399-404.DOI: 10.3969/j.issn.1674-5817.2017.05.011

米非司酮对Wistar大鼠窗口期子宫内膜整合素和血管内皮生长因子基因表达的影响

唐彬, 黎福荣, 付新录, 江国建, 赵勇, 张薇

中山大学实验动物中心, 广州510080

收稿日期:2017-04-20 出版日期:2017-10-25 发布日期:2017-10-25
作者简介:唐彬(1989-),男,硕士,主要从事实验动物研究。E-mail:761284837@qq.com
基金资助:
广东省科技基础条件建设项目(No.2012B060300015)

Effects of Mifepristone on Expression of Integrin α_vβ₃ and Vascular Endothelial Growth Factor in Wistar Rats at Implantation Window Phase

TANG Bin, LI Fu-rong, FU Xing-Lu, JIANG Guo-Jian, ZHAO Yong, ZHANG Wei

Laboratory Animal Center of Sun Yat-sen University, Guangzhou 510080, China

Received:2017-04-20 Online:2017-10-25 Published:2017-10-25

摘要/Abstract

摘要： 目的研究米非司酮对大鼠窗口期子宫内膜整合素(α_vβ₃)、血管内皮生长因子(VEGF)基因表达, 探讨其对子宫内膜超微结构的影响。方法将36只Wistar大鼠分4组,1、2组妊娠1 d后分别服用5 mg/kg、10 mg/kg的米非司酮,3、4组为空白未妊娠组和空白妊娠组,4个组于4.5 d后麻醉取大鼠子宫内膜组织,进行透射电镜观察、ELISA检测血清中雌激素、孕激素含量,同时运用实时荧光定量PCR技术,定量分析整合素α_vβ₃以及VEGF 基因在其子宫内膜中的表达。结果米非司酮能明显抑制Wistar大鼠窗口期子宫内膜α_vβ₃、VEGF基因的表达,同时能显著降低窗口期孕激素的含量(P<0.05),其三者的下调及子宫内膜的超微结构的改变与米非司酮具有明显的剂量依赖关系,对雌激素的含量没有显著影响(P>0.05)。结论米非司酮能在不同程度上降低大鼠整合素α_vβ₃、VEGF基因的表达及孕激素的含量,破坏子宫内膜的超微结构.

关键词: 米非司酮, 整合素(α_vβ₃), 血管内皮生长因子(VEGF), 雌激素, 孕激素

Abstract: Objective To investigate the effect of mifepristone on the expression of integrin α_vβ₃and vascular endothelial growth factor (VEGF) gene, and the effect on ultrastructure of endometrium at implantation window phase in Wistar rats. Methods Thirty-six Wistar rats were divided to four groups, the rats of two experimental groups were orally administered with 5 mg/kg, 10 mg/kg of mifepristone respectively one day after conception. The endometrium was collected 4.5 days after mate both in two experimental groups and two control groups. Ultrastructure of the endometrium were observed by transmission electron microscope, and the expression of integrin α_vβ₃ and VEGF gene in endometrial were tested by RT-PCR method, meantime, the contents of estrogen and progesterone in serum were detected by ELISA technique. Results Mifepristone can inhibits the expression of integrin α_vβ₃, VEGF and progesterone, and increase the content of estrogen (P>0.05). The down-regulation of the three factors and the changes of the ultrastructure of endometrium has obvious dose-response relationship with mifepristone. Conclusion The expression of integrin α_vβ₃ and VEGF gene were decreased differently by mifepristone as well as the content of progesterone, eventually it will affect the ultrastructure of endometrium.

Key words: Mifepristone, Integrin α_vβ₃, Vascular endothelial growth factor (VEGF), Estrogen

中图分类号:

Q95-33

唐彬, 黎福荣, 付新录, 江国建, 赵勇, 张薇. 米非司酮对Wistar大鼠窗口期子宫内膜整合素和血管内皮生长因子基因表达的影响[J]. 实验动物与比较医学, 2017, 37(5): 399-404.

TANG Bin, LI Fu-rong, FU Xing-Lu, JIANG Guo-Jian, ZHAO Yong, ZHANG Wei. Effects of Mifepristone on Expression of Integrin α_vβ₃ and Vascular Endothelial Growth Factor in Wistar Rats at Implantation Window Phase[J]. Laboratory Animal and Comparative Medicine, 2017, 37(5): 399-404.

参考文献

[1] Kim M, Carman CV, Springer TA.Biodirectional trans-memnbrane signaling by cytoplasmic domain separation in integrins[J]. Science, 2003, 301(5640):1720-1725.
[2] Bauer SM, Bauer RJ, Velazquez OC, et al.Angiogenesis, vasculogenesis, and induction of healing in chronic wounds[J]. Vasc Endovascu-lar Surg, 2005, 4:293-306.
[3] Carano RA, Filvaroff EH.Angiogenesis and bone repair[J]. Drug Discov Today, 2003, 21:980-989.
[4] Oxboel J, Binderup T, Knigge U, et al.Quantitative gene- expression of the tumor angiogenesis markers vascular endo thelial growth factor, integrin alphaV and integrin beta3 in human neuroendocrine tumors[J]. Oncol Rep, 2009, 3:769-775.
[5] 王成伟, 庞琦, 张珑, 等. 人脑胶质瘤中微血管密度和血管内皮生长因子表达的意义[J]. 癌症, 2004, 3:326-327.
[6] Senger DR, Gallis J, Dvorak AM, et al.Tumor cells secrete a vascular permeability factor that promote accumulation of ascites fluid[J]. Science, 1983, 219(4587):983-985.
[7] 刘桂君, 陈国江, 黎燕, 等. 血管内皮生长因子在肿瘤生长转移中的作用机制研究进展[J]. 国际药学研究杂志, 2012,39(5):391-395.
[8] Hayashi A, Tanabe A, Kawabe S, et al.Dienogest increases the progesterone receptor isoform B/A ratio in patients with ovarian endometriosis[J]. J Ovarian res, 2012, 5(1):31-38
[9] 陆叶, 于丽, 陈春玲. 雌、孕激素和米非司酮对子宫内膜癌细胞的作用[J]. 北京大学学报, 2005, 37(5):284-286.
[10] Barrier BF.Immunology of endometriosis[J]. Clin Obstet Gynecol, 2010, 53(2):397-402.
[11] Lessey BA, Lebovic DI, Taylor RN.Eutopic endometrium in women with endometriosis: ground zero for the study of implantation defects[J]. Semin Reprod Med, 2013, 31(2):109-124.
[12] Zachary I.VEGF signalling: integration and multi-tasking in endothelial cell biology[J]. Biochem Soc Trans, 2013, 31(1): 1171-1177.
[13] 赵轩, 吴华真, 王宝金, 等. 米非司酮对子宫内膜异位症患者在位及异位子宫内膜中血管内皮生长因子表达及微血管密度的影响[J]. 中华妇产科杂志, 2005, 40(4):277-278.
[14] Gangula PR, SuPowit SC, Wimalawansa SJ, et al. Caleitonin gene-relatedEPtide in a depressor in N(G)-vitro-L-arginine methylester induced hypertension during preaney[J]. Hypertension, 2012, 29(lptZ):248-253.
[15] Reinseh RC, Murphy A, Morales AJ, et al.The effect of RU-486 and leuprolide acetate on uterine blood flow in fibroid uterus: a prospective Randomized study[J]. Am J Obstet Gynecol, 2014, 170(1):1623-1627.
[16] Serini G, Valdembri D, Bussolino F.Integrins and angiogenesis: asticky business[J]. Exp Cell Res, 2006, 312(5):651-658.
[17] Matou S, Colliec-Jouault S, Galy-Fauroux I, et al.Effect of anoversulfated exopolysaccharide on angiogenesis induced by fibroblastgrowth factor-2 or vascular endothelial growth factor in vitro[J].Biochem Phamacol, 2005, 9(5):751-759.
[18] Hosotani R, Kawaguchi M, Masui T, et al.Expression of integrinαvβ3 in pancreatic carcinoma: relation to MMP-2 activation andlymph node metastasis[J]. Pancreas, 2002, 25(2):e30-35.
[19] 谢杏美, 王玉霞. 米非司酮配伍米索前列醇治疗稽留流产和终止10~16周妊娠的效果比较[J]. 实用妇产科杂志, 2012, 28(8):693-695.
[20] 王婷. 米非司酮对子宫内膜作用的研究进展[J]. 现代妇产科进展, 2013, 12(4):295-297.
[21] 马成斌, 刘平, 曹美良. 盆腔子宫内膜异位症术后应用不同剂量米非司酮治疗的疗效观察[J]. 实用妇产科杂志, 2012, 23(1):61-63.
[22] 韩兆忠, 刘茜, 郑伟然. 桂枝茯苓胶囊联合米非司酮治疗子宫肌瘤临床疗效和安全性的系统性评价[J]. 中医药现代化, 2016, 18(3):543-551.
[23] 张恒柱, 武永康, 李耀华, 等. 米非司酮对人脑膜瘤治疗作用的实验研究[J]. 中华神经外科杂志, 2005, 21(1):51-54.
[24] 刘桂君, 陈国江, 黎燕. 血管内皮生长因子在肿瘤生长转移中的作用机制研究进展[J]. 国际药学研究杂志, 2012,39(5):391-395.
[25] 赵公平, 刘兴, 王梦溪. 米非司酮治疗多囊卯巢综合征的疗效观察(附临床病例96例)[J]. 中华妇科杂志, 2008, 10(3):22-23.

米非司酮对Wistar大鼠窗口期子宫内膜整合素和血管内皮生长因子基因表达的影响

Effects of Mifepristone on Expression of Integrin α_vβ₃ and Vascular Endothelial Growth Factor in Wistar Rats at Implantation Window Phase

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 10

编辑推荐

Metrics

本文评价

[1]	马军, 罗居东, 景文江, 张淑莲, 王娟毅, 范志刚. VEGF基因沉默对人肺癌A549细胞放射增敏作用的体内研究[J]. 实验动物与比较医学, 2019, 39(4): 280-286.
[2]	陈林中日, 殷冬来, 赵泽婷, 韦芊含, 陈昕, 张雨梅. 靶向大鼠Vegf/Vegfr基因siRNA的基因沉默效应研究[J]. 实验动物与比较医学, 2019, 39(1): 26-33.
[3]	杨倩, 郁琳, 顾艳, 石燕, 何亚萍, 王健. 米非司酮导致孕激素功能不足的自然流产小鼠模型的建立及其评价[J]. 实验动物与比较医学, 2016, 36(5): 327-333.
[4]	张玥晗, 文静, 朱海桃, 赵光宗, 李晓愚. 雌激素灌胃法制备豚鼠子宫肌瘤模型[J]. 实验动物与比较医学, 2016, 36(3): 195-199.
[5]	韦祝梅, 谢莉萍, 朱琳, 李振明, 梁福东, 杨继红. 双酚A和4-壬基酚对未成年雌性食蟹猴的生殖内分泌毒性作用[J]. 实验动物与比较医学, 2013, 33(5): 351-353.
[6]	许琴, 赵彦斌, 任秀梅, 孙兆增, 叶华虎, 刘一, 李微, 白杰英, 曾林, 胡仲明. 比格犬雌激素受体β的原核表达、纯化及鉴定[J]. 实验动物与比较医学, 2013, 33(3): 174-179.
[7]	马南花1，黎宗强2，覃坚1，郑丽萍1，朱旭1，黄胜贤1，谢莉萍3. 雌性食蟹猴月经周期中血清雌激素、孕激素水平的变化[J]. , 2008, 28(2): 106-109.
[8]	程明军1，俞而慨1，郭方1，王奕森2，徐丛剑1. 转绿色荧光蛋白基因小鼠子宫内膜异位症模型的建立和评价[J]. , 2007, 27(4): 219-221.
[9]	罗惠娟，王自能，孟瑞琳，龚华芳. 米非司酮对晚孕引产大鼠脑组织的影响[J]. , 2001, 21(2): 85-87.
[10]	刘承权, 王忠兴, 胡炎. 甾体激素对豚鼠子宫内膜蜕膜化的影响[J]. , 1996, 16(1): 1-4.

米非司酮对Wistar大鼠窗口期子宫内膜整合素和血管内皮生长因子基因表达的影响

Effects of Mifepristone on Expression of Integrin αvβ3 and Vascular Endothelial Growth Factor in Wistar Rats at Implantation Window Phase

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 10

编辑推荐

Metrics

本文评价

Effects of Mifepristone on Expression of Integrin α_vβ₃ and Vascular Endothelial Growth Factor in Wistar Rats at Implantation Window Phase