Expression And Clinical Significance Of HIF-1α And VEGF In Endometriosis

Objective: To investigate the expression of HIF-1α(hypoxia inducible factor-1α),VEGF(vascular endothelial growth factor) mRNA and and protein in endometriosis, and explore its relationship to angiogenesis,and know better its function in the occurrence and development of endometriosis, which is useful to clinical diagnosis and therapy.Methods:1 The study subject1.1 The study group: 30 patients with ovarian endometriosis who were operated in the gynaecology of the Second hospital of HeBbei medical University were selected from March 2006 to Jun 2007(congfirmed by the pathology after operated). Median age of patients with the study group was 32.6 years old(21 to 38 years old ). And this group is divivided two small groups: eutopic endometrium groups,ectopic endometrium group,each group include 30 cases.1.2 The control group: 15 patients with infertility who were operated with peritoneoscopy during the same hospital and the same periods were chose.The endometrium was confirmed to be normal endometrium through pathology. Median age of patients with control group was 32.4 years old (26 to 35 years old ).All of the women in two groups had normal menstrual cycles; no case history of endocrine and immune and metabolizable diseases,no case history of eating oral esteroid hormone in recent six months;no case history of treating EMs in recent six months. no case history of fixing IUD in recent six months. We distinguished the menstrual cycle on the basia of last mensteual period and the pathology of the endomentrium.1.3 Sample collecting: 30 patients with ovarian endometriosis who were operated with peritoneoscopy in the gynaecology of the Second hospital of HeBei medical University were selected from June 2006 to October 2007(confirmed by the pathology after operated),the ectopic endometrium was collected from the study group on their laparoscopic operatings.At the same time,eutopic endometrium was collected;15 patients with infertility who were operated with peritoneoscopy during the same hospital and the same periods were chose. Parts of the specimen were bathed by the PS again and again,fixed by PFA; Parts of the specimen were bathed by the DEPC again ahd again, immediately cryopreserved at -80℃.2 The experiment methods: To determine the expression of HIF-1αand VEGF in the normal endometrium,eutopic endometrium in endometriosisi and ectopic endometrium in endometriosis by immuno-histechemical staining and RT-PCR. To analyze the results by the means of the SPSS13.0.Results1 HIF-1αprotein was localized in glandular epithelial cells in the ectopic (Fib.1) and eutopic endometrium (Fib.2) of endo- metriosis and in the normal endometrium of control group (Fig.3) .But individual stromal cells have expression too. VEGF protein was localized in intracytoplasm of glandular epithelial cells, stromal cells, and endothelial cells in the ectopic (Fib.4) and eutopic endometrium of endometriosis (Fib.5)and in the normal endometrium of control group(Fib.6). The express- ion level of VEGF was stronger in the glandular epithelial cells than in the stromal cells.2 The expression of HIF-1αand VEGF protein in the the ectopic and eutopic endometrium of endometriosis and in the normal endometrium of control group: The positive ratio of HIF-1αprotein in the the ectopic and eutopic endometrium of endometriosis and in the normal endometrium of control group was 86.6%, 30.0%,and 0%(Tab.1). The positive ratio of VEGF protein in the the ectopic and eutopic endometrium of endometriosis and in the normal endometrium of control group was 90.0 %,66.6%, and 20%(Tab.2). The expression level of HIF-1αand VEGF protein in ectopic and eutopic endometrium of endometriosis was markedly higher than that in control group(P<0.05). The expression level of HIF-1αprotein in the ectopic endometrium of endometriosis was markedly higher than that in the eutopic endometrium of endometriosis(P<0.05), The expression of HIF-1αprotein in menstruate periods of the eutopic endometrium of endometriosis and normal endometrium had no significance. While the expression level of VEGF protein in the eutopic endometrium of endometriosis was markedly higher than that in the ectopic endometrium of endometriosis(P<0.05), The expression of VEGF in menstruate periods of the eutopic endometrium of endometriosis had no significance.There was a positive relationship between the expression of HIF-1αprotein and VEGF protein in ectopic endometrium of endometriosis(r=0.73, P<0.05) ( Tab.5).and in eutopic endome- trium (r=0.68, P<0.05 )( Tab.6).3 The expression of HIF-1αand VEGF mRNA in the endometriosis: The expression level of HIF-1αmRNA in the ectopic endometrium(0.789±0.326)and in the eutopic endometrium(0.295±0.154) was markedly higher than that in the normal endometrium (0.124±0.012) (t=33.51,P<0.05);While the expression level of HIF-1αmRNA in the ectopic endometrium was markedly higher than that in the eutopic endometrium of endometriosis(t=26.30,P<0.05)(Tab.3). The expression level of VEGF mRNA in the ectopic endometrium(8.160±5.342),and in the eutopic endometrium(11.521±7.420) was markedly higher than that in the normal endometrium(2.770±1.028()t=43.98,P<0.05);There was no significant difference in VEGF mRNA levels between ectopic endometrium and eutopic endometrium of endometriosis(t=3.09,p>0.05)(Tab.4)。There was a positive relationship between the expression of HIF-1αmRNA and VEGF mRNA in the ectopic endometrium of endometriosis(r=0.83,P < 0.05). and in the eutopic endometrium(r=0.72, P<0.05) (Tab.7).Conclusion:1 The expression level of HIF-1αprotein and mRNA in ectopic and eutopic endometrium of endometriosis was markedly higher than that in control group. The expression level of HIF-1αprotein in the ectopic endometrium of endometriosis was markedly higher than that in the eutopic endometrium of endometriosis.2 The expression level of VEGF protein and mRNA in ectopic and eutopic endometrium of endometriosis was markedly higher than that in control group.The expression level of VEGF protein in the eutopic endometrium of endometriosis was markedly higher than that in the ectopic endometrium of endometriosis. The expression of HIF-1αprotein and mRNA have no cyclic changes in normal endometrium and endometriosis.The expression of VEGF showed obvious cyclic changes in normal endometrium, but these changes disappeared in the eutopic endometrium of endometriosis.3 A positive correlation was found between HIF-1αand VEGF expression in endometriosis. It revealed that HIF-1αcan accelerate VEGF expression in endometriosis.4 Statiscal analysis revealed that both HIF-1αand VEGF expression were higher in endometriosis tissues than that in normal endometrium tissues. HIF-1αand VEGF were associated with the occurrence and development of endometriosis.