铜/低密度聚乙烯复合材料宫内节育器引起子宫异常出血与铜离子浓度和血管生成的相关性

Copper ion concentration and angiogenesis as two correlates to abnomal uterine bleeding caused by copper/low-density polyethylene nanocomposite intrauterine device

背景:含铜宫内节育器表面的铜丝在宫腔内持续释放铜离子,避孕效果明显,但容易发生节育器异位、子宫异常出血、经期延长、腰腹酸痛等不良反应。目的:探讨铜/低密度聚乙烯复合材料宫内节育器致子宫异常出血与子宫内膜组织中铜离子浓度及血管内皮生长因子表达的关系。方法:纳入取铜/低密度聚乙烯复合材料宫内节育器女性患者60例,年龄25-40岁,分为子宫异常出血组(n=32)和无出血组(n=28);另选择未放置宫内节育器且月经周期正常的女性为对照组(n=20)。子宫异常出血组与无出血组在月经干净后4-7 d内取宫内节育器的同时,刮取子宫内膜组织;对照组月经干净后4-7 d内刮取子宫内膜组织。采用原子吸收法测定子宫内膜组织铜离子含量,免疫组织化学染色检测子宫内膜血管内皮生长因子表达,计数微血管密度;火焰原子吸收法测定模拟宫腔液中宫内节育器铜离子溶蚀量。结果与结论:(1)铜离子含量:子宫异常出血组高于无出血组(P<0.05),无出血组高于对照组(P<0.05);(2)铜离子溶蚀量:子宫异常出血组高于无出血组(P<0.05);(3)组织学观察:与无出血组和对照组相比,子宫异常出血组血管内皮生长因子蛋白表达和微血管密度明显增加(P<0.05);无出血组与对照组内皮生长因子蛋白表达与微血管密度比较差异无显著性意义;(4)子宫内膜血管内皮生长因子表达与微血管密度、铜离子含量呈正相关(P<0.05)。(5)结果表明:铜/低密度聚乙烯复合材料宫内节育器置入后,子宫内膜组织中铜离子浓度过高可能引起血管内皮生长因子高表达,血管内皮生长因子通过多种途径增加子宫内膜微血管密度,促进微血管扩张、充血,导致子宫异常出血。

BACKGROUND：Toachieve excelent contraceptive effects,the copper wire on the copper-containing intrauterine device surface persistently releases copper ions, but ectopic intrauterine device, abnormal uterine bleeding, menostaxis and waist and abdominal painareusualyinevitable. OBJECTIVE：To investigate the correlation of abnormal uterine bleedingcausedby copper/low-density polyethylenenanocompositeintrauterine devicewith copper ion concentration and expression of vascular endothelial growthfactor in endometrial tissues. METHODS：Totaly 60femalepatients, aged from 25 to 40 years old, hospitalizedfor taking intrauterine devices were enroled, and those patients were divided into abnormal uterine bleeding group （n=32） and non-bleeding group （n=28）. In the meanwhile,another20women without intrauterine devicesand with the normal menstrual cycle were selected as control group. Patients in the abnormal uterine bleeding group and non-bleeding group underwenttheremoval of intrauterine device and scraping endometrial tissues within 4-7 days after menstruation; patients in the control group underwentscraping endometrial tissues within 4-7 days after menstruation. The copper ion content in endometrial tissues was measured by atomic absorption method;expression of endometrial vascular endothelial growth factor detected by immunohistochemical stainingand the microvessel density counted.Additionaly, the corrosionratio of copper ion in the simulated uterine fluid was detected using flame atomic absorption spectroscopy method. RESULTS AND CONCLUSION：The content and corrosionratio of copper ion in theuterine abnormal bleeding group was significantly higher than thoseinthe non-bleeding group （P〈 0.05）, and the copper ion content of no bleeding group was significantly higher than that of control group （P〈 0.05）. The amount of copper in the intrauterine device of abnormal uterine bleeding group was higher than thatin non-bleeding group （P〈 0.05）.Compared with the control andnon-bleeding groups, the vascular endothelial growth factor expression and microvessel density were significantly increasedin the uterine abnormal bleeding group（P〈 0.05）; and the control group and non-bleeding group had no significant differencesinthe vascular endothelial growth factor expression and microvessel density. Furthermore, there was a positive correlationofthevascular endothelial growth factor expressionwithmicrovessel density and copper ion content. In conclusion, after implantation ofcopper/low-density polyethylene nanocompositesintrauterine device, the higher copper ion concentration in endometrial tissues may lead to the over-expression of vascular endothelial growth factorthatincreases the endometrial microvessel density througha variety of ways, and promotemicrovesselexpansion and congestion, finaly resulting in abnormal uterine bleeding.