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

BACKGROUND: To achieve excellent 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 pain are usually inevitable.OBJECTIVE: To investigate the correlation of abnormal uterine bleeding caused by copper/low-density polyethylene nanocomposite intrauterine device with copper ion concentration and expression of vascular endothelial growth factor in endometrial tissues.METHODS: Totally 60 female patients, aged from 25 to 40 years old, hospitalized for taking intrauterine devices were enrolled, and those patients were divided into abnormal uterine bleeding group (n=32) and non- bleeding group (n=28). In the meanwhile, another 20 women without intrauterine devices and with the normal menstrual cycle were selected as control group. Patients in the abnormal uterine bleeding group and non- bleeding group underwent the removal of intrauterine device and scraping endometrial tissues within 4-7 days after menstruation; patients in the control group underwent scraping 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 staining and the microvessel density counted. Additionally, the corrosion ratio of copper ion in the simulated uterine fluid was detected using flame atomic absorption spectroscopy method.RESULTS AND CONCLUSION: The content and corrosion ratio of copper ion in the uterine abnormal bleeding group was significantly higher than those in the 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 that in non-bleeding group (P < 0.05). Compared with the control and non-bleeding groups, the vascular endothelial growth factor expression and microvessel density were significantly increased in the uterine abnormal bleeding group (P < 0.05); and the control group and non-bleeding group had no significant differences in the vascular endothelial growth factor expression and microvessel density. Furthermore, there was a positive correlation of the vascular endothelial growth factor expression with microvessel density and copper ion content. In conclusion, after implantation of copper/low-density polyethylene   nanocomposites intrauterine device, the higher copper ion concentration in endometrial tissues may lead to the over-expression of vascular endothelial growth factor that increases the endometrial microvessel density through a variety of ways, and promote microvessel expansion and congestion, finally resulting in abnormal uterine bleeding.