| BackgroundThe womb gland myopathy (Adenomyosis) refers to the endometrial glands and stroma to the muscle layer and in which benign infiltrative diffuse growth [1], is a common gynecological disease, multiple in30-50women [2], the pathogenesis remains unclear, the main clinical manifestations of secondary progressive excessive menstruation, dysmenorrhea, menstrual extension, infertility, to the vast number of women’s physical and mental health and quality of life caused serious harm. The disease incidence in recent years there is an increasing trend, and gradually tended to be younger [3], drugs and conservative operation curative effect is not ideal, effective treatment is to hysterectomy,[4]the desire for childbearing women clinical treatment is very difficult, so the study of Adenomyosis occurrence and development mechanism, solve the improvement of symptoms, eradication of the lesion, to preserve the uterus, increase pregnancy rate and a series of problems, to find new effective therapeutic way to become a hot topic in the research of AdenomyosisMany studies showed that Adenomyosis hat patients with Adenomyosis lesions within uterine endometrium, myometrium, the blood vessels in the area and number of significantly increased significantly compared with the normal uterus. Some scholars through the pituitary transplantation of mouse uterine adenomyosis model [6], adenomyosis of uterus, uterine endometrium of primary vascular diameter, vascular area to increase significantly. Visible Adenomyosis having angiogenic properties, so the study on the regulation of angiogenesis of some important factors such as vascular endothelial growth factor (VEGF), hypoxia inducible factor-1(HIF-1), endostatin (ENS), microvascular density (MVD) in AM expression, on the understanding of its pathogenesis, from inhibition angiogenesis perspective to explore new methods for the treatment of Adenomyosis has important significance.VEGF is also called vascular permeability factor (VPF), is the in vivo and in vitro vascular endothelial growth specific mitogen, is separated from the secretion of tumor cells of a glycoprotein, has powerful procoagulant endothelial proliferation, angiogenesis effects. At the same time, VEGF can promote increased vascular permeability, exudation of plasma protein, forming a fibrous matrix, induced in fibroblasts, endothelial cells and inflammatory factors of hyperplasia. High activity of VEGF, high specificity, in numerous angiogenic factors is in the core status, its tissue expression levels reflect the organization of vasoactive [7,8], other angiogenic factors mostly through enhanced VEGF expression produces angiogenic effect of [9,10].HIF-1is anoxic condition number expression of a transcription factor, through the addition of anaerobic metabolism, inducing angiogenesis and tumor cells in the hypoxic environment survival, metastatic ability [11]. Studies show that, HIF-1a on VEGF expression has a regulatory role [12].ENS is an endogenous inhibitor of angiogenesis, is the first from the cultured rat vascular endothelial tumor cell culture fluid extracted, all tissue intravascular, skin basement membrane zone, alveolar basement membrane zone and skin epidermal basement membrane zone has its binding site, hypoxia, stress and interferon are to promote the ENS attack release, studies show, ENS on vascular endothelial cell growth inhibition strength the strongest, with VEGF receptor competitive binding, making angiogenesis signaling pathways are blocked, inhibition of endothelial cell angiogenesis and proliferation.MVD is the assessment of angiogenesis index, quantitative analysis of MVD depends on the expression of CD34, CD34for vascular endothelial cell specific markers [13], with the acceleration of vascular endothelial cell aggregation, adhesion, before formation of blood vessels, regulating hematopoietic cell proliferation and differentiation function. CD34is widely used in measuring various tissues of MVD value, organization of higher values of MVD description of new capillaries more rich [14].ObjectiveThe purpose of this project is to study VEGF, HIF-1, MVD, ENS in AM ectopic, eutopic endometrium and normal endometrium in the expression and correlation of AM, pathogenesis, from preserving the uterus, meet the needs of the young patients with planning requirements and improve the life quality of patients with such areas to seek new effective drug treatment to provide a new thinking and a strong theoretical basis.Methods1, specimen collection, production, grouping and screening:Study group:2009August to2011August were collected, in the people’s Hospital of Xinzhou city for Adenomyosis hysterectomy operation in60cases, in which the normal menstruation in18cases,42cases of menorrhagia are, without dysmenorrhea in24cases,36cases of dysmenorrhea, age36-51years old.60cases of Adenomyosis patients with ectopic endometrial tissues as the study group of1, of which34cases of proliferative, secretory phase in26cases; the eutopic endometrial tissue as a study group of2, including secretory phase in28cases,32cases of proliferative phase.All cases within3months were not using hormonal history, exclusion of combined immune system disorders and other disorders of the endocrine system, all tissue sections by the pathologist verification confirmed, sections were stained with HE, screening without chronic inflammatory changes and no complicated with endometrial polyp tissues as study group specimens.Control group:Collection period due to cervical gland cyst, cervical erosion and chronic cervicitis and CIN II level line conization in48cases, exclusion of adenomyosis, uterine fibroids, endometriosis case, age28years old-46years old,In the case of the downlink of informed consent of patients taking endometrial curettage, normal secretory phase in20cases,28cases of proliferative phase.In48patients3months are not used hormone, exclusion of combined immune system disorders and other disorders of the endocrine system, all tissue sections by the pathologist verification rule Adenomyosis, sections were stained with HE, screening without chronic inflammatory changes and no complicated with endometrial polyp tissues as observation group specimens.2, detection method:By immunohistochemical SP method (streptomycin avidin a peroxidase connection method) in strict accordance with the procedures for staining, using PBS instead of a resistant reaction for negative control, respectively, for detection of VEGF, HIF-1, MVD, ENS expression.ResultsIn1, VEGF in proliferative and secretory endometrium, eutopic and ectopic endometrial tissue of expression is enhanced, the average water (P<0.05), the secretory phase of normal endometrium and eutopic endometrial tissue VEGF expression was significantly higher in the proliferative phase (P<0.05), ectopic endometrial tissue VEGF expression in proliferative and secretory phase without obvious difference (P>0.05).In2, the ectopic endometrial tissue of MVD was significantly higher than the corresponding eutopic endometrium and normal endometrial tissue (P<0.05).In3, HIF-1proliferative normal endometrium and eutopic endometrial tissue in the expression or weakly positive expression in ectopic endometrial tissue, was strongly positive or moderate expression (P<0.05); the secretory phase of the normal endometrium, ectopic endometrium and ectopic endometrial tissue of expression than those in proliferative phase was significantly enhanced (P<0.05), ectopic endometrium, ectopic endometrium and normal endometrial tissue in HIF-1expression once enhanced (P<0.05).In4, ENS expression in each group showed no significant differences (P>0.05).In5, VEGF, and MVD was positively correlated with VEGF, MVD, HIF-1positively correlated.ConclusionsIn1, VEGF, HIF-1, MVD Adenomyosis in ectopic endometrium and eutopic endometrium of a high level expression, prompting the formation of new blood vessels and the local blood supply and the onset of Adenomyosis; VEGF relative over-expression can improve the endometrial angiogenesis activity, make local blood supply is abundant, causes blood vessels to invade the myometrium and infiltration growth.2, adenomyosis of the tissue microenvironment hypoxia condition, this condition HIF-1overexpression, it through activation of the VEGF transcription, promote new angiogenesis in endometriosis, make MVD showed high levels of expression, and participate in the occurrence and development of disease.3, angiogenesis is the development of Adenomyosis key, the formation of new blood vessels depends on various positive and negative regulators of balance, the lesions improved state of hypoxia, blocking the HIF-1a effect, inhibition of VEGF, MVD expression, anti angiogenesis, is Adenomyosis conservative therapy, is Adenomyosis new directions for treatment, clinical of great significance. |
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