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Establishment Of A Rhesus Model For Endometriosis And The Study Of The Mechanisms Involved

Posted on:2005-07-22Degree:DoctorType:Dissertation
Country:ChinaCandidate:L L ZongFull Text:PDF
GTID:1104360122998585Subject:Pharmacology
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Background:Endometriosis (EM), defined histologically as a pathological entity of the presence of endometrium-like glands and stroma outside the uterus, with a morbidity as high as 10-15%. It seems that the condition shows a trend with gradual increase among the population. It shares features with malignant tumors (invasion and metastasis) but is not neoplastic. Despite of the fact that endometriosis is one of the most frequent gynaecological diseases, the mechanism is still under detailed scrutiny with some controversy. The aetiology and pathogenesis is little understood at present. Sampson's theory of retrograde menstruation is dominated in the field at the moment, under which the endometrial cells, who have some potentials and are sensitive to estrogen during the menstrual period, are transported though Fallopian tubes into the peritoneal cavity where they implant, proliferate. This process would in turn enhance angiogenesis and eventually develop into endometriotic lesions. This theory is now matured as a so-called implantation theory. Establishment of an endometriosis model based on the implantation theory and the study on the role of immune system and some cytokines that is correlative with cell invasion and metastasis in pathogenesis of endometriosis would be valuable for our thorough understanding of the invasion mechanism of endometriosis. This approach will also provide some clues leading to a new treatment strategy for endometriosis.Part I Establishment and characterization of the endometriosis model in rhesus Objectives:To establish the experimental endometriosis model in rhesus and to further observeof the life habit and physiological changes; Furthermore to investigate the dynamics of the parameters in the immune system, including T cell and NK cell sub-populations, cytokines, such as HGF ICAM-1 TNF-a IL-6 IL-8 and tumor marker CA125, antibodies (IgG, IgM) during endometrial cells implantation, proliferation and forming of endometriosis.Materials and Methods:1. Six female healthy rhesuses with regular menstrual cycle were selected, among them, five for experiment and one as control. During day 8-15 of menstruation, or day 3-5 after the midcycle estrogen peak, the endometrium and the greater omentum were implanted into the extra-uterine pelvic cavity in the experimental group and the control group, respectively.2. Samples of sera were collected at the time of 8th day of every menstruation after the implantation. An exploratory laparotomy or laparoscopy was undertaken during the period from day 8 to day 15 of the menstruation in the 2nd month and the 4th month after the implantation for observation of the occurrence of endometriosis. At the same time tissue samples and peritoneal fluids were collected.3. Flow cytometer (FCM), radioimmuno-assay (RIA), electrochemiluminescence (ECL) and enzyme-linked immunosorbent assay (ELISA) were used to detect the dynamics of the expression levels of CD3, CD4, CD8, CD 16 and activity of NK cells, the dynamics of the IgG. IgM, of cytokines, including TNF-a IL-6. IL-8 CA125 HGF and ICAM-1 in peripheral blood of rhesus pre-operation and during the three months of post operation.Results:1. In the experimental group, the implanted endometrium survived in the acceptor site in 4 rhesuses, of whom 2 was found having ectopia cyst after two months of the operation. A laparoscopy was performed on 2 of the rhesuses with endometriosis in month 4 after the operation. Pelvic adhesion and growth of ectopic endometrium were similar to thosein month 2 post-operation. The mental and dietary statuses and body weight of the models with endometriosis were worse than those of the control, and 3 rhesuses even died of intussusception.2. In the ectopia tissue section, endometrial stroma cell and endometrium gland (either intact or unintact) could be seen with abundant capillary. Some of the glands in ectopic endometrium were complete, whereas others were incomplete. Meanwhile, some of them were synchronized with that in eutopic endometrium,...
Keywords/Search Tags:endometriosis, rhesus, rat, model, hepatocyte growth factor (HGF)
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