The Significance of Angiopointin-1,-2 Expressions in the Endometrium of Women with Abnormal Bleeding Induced by Intrauterine Device
|Course||Obstetrics and Gynaecology|
|Keywords||Angiopoietin IUD Endometrial Bleeding|
Background intrauterine device (IUD) as a safe, effective, long-acting, reversible contraceptive measures widely used in our country, but its side effects has yet to properly resolve the cause abnormal uterine bleeding, affect the renewal rate reasons. Abnormal bleeding after the set is mainly manifested as excessive menstrual flow, prolonged menstrual period and spotting. Domestic and international studies have shown that the IUD cause abnormal uterine bleeding caused by a variety of factors, including abnormal endometrial prostaglandin synthesis, increased fibrinolytic activity, increased local inflammatory response, but this can not satisfactorily explain the anti-prostaglandin antifibrinolytic and anti-inflammatory drugs are not effective in all cases. The existence of cyclical growth and shedding, accompanied by a variety of vascular endothelial growth factor regulation periodic blood vessel growth in the endometrium. To IUD insertion abnormal bleeding endometrial abnormal vascular structure performance for superficial spiral artery dilatation associated with spiral arterial wall and endothelial cell degeneration, vascular endothelial growth factor (VEGF) and increased expression and microvessel density increase. Thus, we speculated that the structure and function the IUD caused by irregular uterine bleeding may be the expression of various growth factors caused by abnormal blood vessels disorders related. The angiopoietin (angiopoietin, Ang) is a vascular endothelial growth factor found in recent years, mainly there are two subtypes of Ang-1 and Ang-2, both of which are involved in the regulation of angiogenesis and inflammation of the blood vessels in the stable, in the embryo and play an important role in the adult physiological and pathological angiogenesis. Ang-1 induction of the latter by binding to the endothelial cell specific tyrosine enzyme receptor (Tie-2) autophosphorylation and subsequently promote neovascularization surrounding support cell aggregation, reducing vascular permeability, thus contributing to stable neovascularization increases. In addition, Ang-1 also promote the stability of inflammation in the blood vessels and inhibition of endothelial cell apoptosis role. Combined Ang-2 competition and Tie-2, but not caused by its phosphorylation, thereby blocking the role of Ang-1, stromal cell degradation of perivascular decreased stability to promote neovascularization budding, in the presence of VEGF and other, and vice versa resulting in degradation vascular. Ang-2 is also involved in the induction of inflammatory reaction. Ang-1 and Ang-2 expression in human endometrium. Was progesterone-dependent expression of Ang-1, increased expression of secretory endometrium. Decline menorrhagia endometrial expression of Ang-1. Ang-2 expression did not change significantly with the menstrual cycle, but vitro hypoxia the inflammatory factor can up-regulate Ang-2 expression in human endometrial endothelial cells. This shows that Ang-1 and Ang-2 may be involved in the physiological and pathological endometrial angiogenesis. This study collected after IUD insertion abnormal bleeding as the research object and detect endometrial of Ang-1, Ang-2 and Tie-2 mRNA levels of Ang-1, of Ang-2 in the level of protein expression changes aimed provide new ideas for the angiogenesis discusses the mechanism of the occurrence of the side effects of the IUD bleeding after IUD insertion for the treatment of abnormal bleeding. Materials and methods Source: 2006.3 to 2007.3 at Zhejiang University School of Medicine, Obstetrics and Gynecology Hospital outpatient women, the case group to meet the following conditions: ① the ages of 25 to 45 years old; ② three consecutive months of unused steroid IUD insertion menstrual regularity hormone drugs; ③ through the normal amount, placed increased significantly after prolonged menstrual period (> 8d); ④ B super exclude the menstrual caused by uterine fibroids, adenomyosis, endometrial polyps too much; ⑤ placed life of 0.5 to 10 years; ⑥ without liver disease, history of blood diseases; ⑦ exclude placed the levonorgestrel-releasing intrauterine system containing indomethacin of IUD. The case group of 33 cases, including 23 cases of proliferative phase, 10 cases of secretory phase. The control group, 28 cases of normal endometrial hyperplasia and 12 cases, 16 cases of secretory phase. Various groups were comparable in age, take intima time. The tissue is divided into two, one into the quick-frozen in liquid nitrogen and placed in 10% neutral buffered formalin fixed another. Ang-1, Ang-2 and Tie-2 mRNA expression by reverse transcription - polymerase chain reaction (RT-PCR) to detect and Immunohistochemistry was used to detect the expression of Ang-1 and Ang-2 protein. H-Score method for semi-quantitative Ang-1 and Ang-2 staining. Ang-1, Ang-2, Tie-2 mRNA relative optical density and Ang-1 and of Ang-2 H-Score integral line independent samples t-test and non-parametric test. The results of a group expression of Ang-1, Ang-2 and Tie-2 mRNA in the change can be detected in human endometrium to Ang-1, Ang-2 and Tie-2 mRNA expression. Set the IUD group of endometrial proliferative and secretory phase of Ang-1 expression were decreased (p <0.05). With IUD group secretory phase Tie-2 expression, as well Ang-1/Ang-2 proportion decreased significantly (p <0.05) compared with the normal secretory phase. 2, Ang-1 expression in endometrial Ang-1 was mainly expressed in endometrial glandular epithelial luminal epithelial and endothelial cells, stromal cells express weak. The increase in secretory endometrium Ang-1 expression in the around spiral arteries Decidualization the stromal cells, especially increased. IUD insertion bleeding visible part of the spiral arteries dilate and vascular endothelial cells absent. Ang-1 in each group H-Score Points suggest that increased expression of Ang-1 normal secretory phase endometrium (p <0.001). Proliferative endometrium with IUD group of Ang-1 in the glands and stroma express both plus and decreased (p <0.001); expression of Ang-1 with IUD secretion of endometrial glands decreased (p < 0.01). 3, Ang-2 in endometrial expression of Ang-2 is mainly expressed in endometrial epithelial luminal epithelial and endothelial cells, stromal cell expression of Ang-1 weaker. Ang-2 expression in normal secretory endometrium glands than the proliferative phase to reduce (p <0.05); Ang-2 set the IUD group of secretory phase glands than normal secretion increased (p <0.05). Conclusion 1. Protein Ang-1 and Tie-2 mRNA in normal endometrium secretory phase than the proliferative phase increased expression of Ang-2 protein in normal secretory phase than the proliferative phase decreased expression, which may contribute to the stability of the secretion of vascular. 2. IUD insertion abnormal bleeding endometrial Ang-1 mRNA and protein, Tie-2 mRNA expression was decreased, accompanied by Ang-2 protein expression increased, which may affect vascular function and participate in the bleeding side effects of the IUD.