| ObjectiveEndometriosis (EMs) is a benign gynecological disease caused by the active endometrial cells which had appeared and flourished outside the uterine.Its pathogenesis is very complex. In recent years, studies had shown that: neovascularization plays an very important role in the progress of endometriosis. Regulation of angiogenesis may take the treatment of endometriosis to a brand-new field. Delta like ligand4(DLL4) is a new angiogenic regulators on which studies only in cancer tissues, and none report on its expressions in tissue of EMs. Hypoxia inducible factor-1(HIF-1) is the only core control factor that plays an activity role when body in hypoxic conditions, and can interact with a variety of factors involved in angiogenesis; vascular endothelial growth factor (VEGF) is a promote angiogenesis factor which was founded has the most widely and the strongest function in the whole process of angiogenesis. Now, none literature has reported on the jointly detection about the expressions and the correlationship of the three kinds of protien in the ectopic endometrium and eutopic endometrium of endometriosis.In this study, the expressions of DLL4、HIF-1and VEGF in ectopic endometrium and eutopic endometrium were jointly detected by the immunohistochemical S-P method, and compared to normal endometrium.Then, analyze their correlationships with eachother and their expressions in different clinical stage in EMs, aiming to investigate the role of DLL4, HIF-1and VEGF in the progression of EMs, and provides theoretical basis on the pathogenesis and clinical studies for EMs.MethodsExperimental groups:83patients with "ovarian cyst" were selected from August2011to October2012in the Department of Gynecology from the Second Affiliated Hospital of Zhengzhou University, which were comfromed for "chocolate cyst of ovary" after laparoscopic surgery and postoperative pathology. Group A: took "ovarian ectopic endometrium",after HE staining,48cases were selected in the test. Group B:Among83patients,37cases who had fertility requirements were treated by the hysteroscopy operation at the same time,excepted the endometrial lesions, took "eutopic endometrium". American fertility association revised standard (r-AFS) in1985was used to divide the clinical stage:Group A:Ⅰ～Ⅱ stage21cases, Ⅲ～Ⅳ27cases; Group B:Ⅰ～Ⅱ stage16cases Ⅲ～Ⅳ stage21cases.Control group:Group C:30cases was selected in the same period in the Department of Gynecology from patients with "septum uterus",who were given the treatment of "Hysteroscopic resection of uterine septum", excepted the endometrial lesions,took "normal endometrium".All patients above had no other complications on physicians and surgeons,and all of them had regularly menstrual cycle of28d～35d.Excluding endocrine diseases,adenomyosis or anyother diseases of gynecological, such as endometrial diseases and genital tract inflammation and so on. None of them had hormone treatment at least half a year.The expressions of DLL4、HIF-1and VEGF protein in group A, B and C were jointly detected by the immunohistochemical S-P method,then analyze their correlationship with eachother in each group and their expressions in different clinical stage in EMs. All data analysised by statistical software SPSS17.0. One-way ANOVA used for Multiple sets of quantitative data, LSD test used for multiple comparison, Independent-samples t test used for two groups of independent sample comparison, Pearson product-moment correlation coefficient used for Continuous random variable correlation analysis. Inspection level of a=0.05.Results1. DLL4%HIF-1and VEGF protein mainly expressed in the cytoplasm of gland epithelial cells in ectopic endometrium and eutopic endometrium in patients with EMs,and little expressed in the cytoplasm of stromal cells.2. In group A, B and C,the expressions of DLL4were (145.01±10.47)、(115.56±10.87)、(90.08±8.56), F=279.113,P=0.000; the expressions of HIF-1were (146.71±8.73)、(118.91±8.00)、(100.99±6.63), F=322.420、P=0.000; the expressions of VEGF were (148.48±8.36)、(122.79±5.68)、(108.75±7.39),F=296.049、P=0.000. Comparison between any two means,the expressions of DLL4、HIF-1and VEGF protein in group A and B were much higher than that in group C (P<0.05). The expressions of DLL4、HIF-1and VEGF protein in group A were much higher compared to that in group B (P<0.05).3. In group A,the expressions of DLL4、HIF-1and VEGF protein at stage I-II of EMs were (136.37±5.84)、(139.84±5.50) and (143.08±5.08), and at stage III-IV their expressions were (151.73±8.03)、(152.05±6.84) and (152.68±8.04). In group B, the expressions of DLL4、HIF-1and VEGF protein at stage Ⅰ～Ⅱ of EMs were (107.13±7.47)、(112.01±4.17) and (119.04±4.12), and at stageⅢ～Ⅳ their expressions were (121.98±8.41)、(124.16±5.91) and (125.65±5.04).In group A and B, the expressions of DLL4、HIF-1and VEGF protein at stage I II were lower than that at stage Ⅲ～Ⅳ (P<0.05).4. The expressions of DLL4、HIF-1and VEGF protein in group A and B had positive correlation with eachother (P<0.05), while in group C, their expressions showed none correlation、0.05).(In group A, the expressions of DLL4were positively correlated with that of HIF-1and VEGF, r=0.881and r=0.828, the expressions of HIF-1were positively correlated with that of VEGF, r=0.838. In group B, the expressions of DLL4were positively correlated with that of HIF-1and VEGF, r=0.824and r=0.773, the expressions of HIF-1were positively correlated with that of VEGF, r=0.707. In group C, the expressions of DLL4were positively correlated with that of HIF-1and VEGF, r=0.257and r=0.171, the expressions of HIF-1were positively correlated with that of VEGF, r=0.151). Conclusions1. DLL4、HIF-1and VEGF protein may play an very important role in the progress of EMs.2. DLL4、HIF-1and VEGF protein may play a mutual synergy role with eachother in the progress of EMs. |
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