三苯氧胺联合米非司酮药物流产对早孕绒毛VEGF、TGF-β_1表达的影响

Effect of Tamoxifen Combined with Mifepristone on VEGF and TGF-β_1 Expression in Early Pregnancy Chorionic Villi

目的:探讨三苯氧胺联合米非司酮药物流产缩短流产后出血时间的可能机制。方法:将非意愿妊娠49d内要求药物流产的宫内早孕妇女50例随机分成,米非司酮+三苯氧胺组(A组):给予三苯氧胺120mg联合米非司酮150mg配伍米索前列醇600μg;米非司酮组(B组):将三苯氧胺换成安慰剂余同A组。应用免疫组化Envision法检测内自然排出绒毛组织中血管内皮生长因子(VEGF)、转化生长因子(TGF-β1)的表达,用Image-Pro Plus4.5图像分析软件测定VEGF、TGF-β1蛋白表达积分光密度值,并以21例负压吸宫流产绒毛组织为对照组(C组)。结果:VEGF蛋白在全部合体滋养细胞、细胞滋养细胞和血管内皮细胞表达,间质细胞大部分表达;TGF-β1蛋白在大部分合体滋养细胞和细胞滋养细胞表达,间质细胞和血管内皮细胞少量表达。A、B、C组绒毛VEGF、TGF-β1蛋白表达积分光密度值依次升高,VEGFIOD值分别为:33452.49±10666.87、42436.74±12979.98和53954.56±15946.22,TGF-β1IOD值分别为:29823.02±12357.60、40880.01±18022.13和59915.28±19219.37,两两比较,其差异有统计学意义,P值均<0.05。结论:米非司酮抑制VEGF、TGF-β1在绒毛组织的表达可能是其抗早孕机理之一,而三苯氧胺可进一步加强米非司酮的这一作用,这可能是其缩短米非司酮药物流产后出血时间的机制之一。

Objective： To investigate the possible mechanism of tamoxifen combined with mifepristone on shortening the duration of vaginal bleeding after medical abortion. Methods： Fifty women within 49 d of intrauterine gestation were randomly divided into two groups. Tamoxifen 120 mg combined with mifepristone 150mg was administered orally to the group A, followed by misoprostol 600μg orally. Placebo combined with mifepristone 150 mg was administered orally to the group B, followed by misoprostol 600 μg orally. Twenty one women who selected vacuum aspiration were as control group（group C）. Chorionic villi were collected and expression of VEGF and TGF-β1 were detected by immunohistochemical methods. Integrated optical density （IOD） of VEGF and TGF-β1 was detected by using special image analysis software. Results： VEGF protein was expressed in all syncytiotrophoblast cells, cytotrophoblast cells and vascular endothelial cells, and was expressed in interstitial cells mostly. TGF-β1 protein was expressed mostly in syncytiothrophoblast cells and cytotrophoblast cells, and little in interstitial cells and vascular endothelial cells. IOD of VEGF and TGF-β1 expression of group C, group B, group A reduced one by one. The difference between any two group was significant statistically （P〈0.05） （IOD of VEGF： 53 954.56 ± 15 946.22, 42 436.74 ± 12 979.98 ＆ 33 452.49 ± 10 666.87; IOD of TGF-β1： 59 915.28 ± 19 219.37, 40 880.01 ± 18 022.13 ＆ 29 823.02 ± 12 357.60）. Conclusion： It is speculated that mifepristone resists early pregnancy because it suppresses the expression of VEGF and TGF-β1 on chorionic villi.Tamoxifen could strengthen this effect of mifepristone, so it could shorten the duration of vaginal bleeding after medical abortion.