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Nuclear Factor NF-κB Endometriosis In The Rat The Role Of Pathogenesis

Posted on:2012-04-06Degree:MasterType:Thesis
Country:ChinaCandidate:J NingFull Text:PDF
GTID:2154330332996473Subject:Obstetrics and gynecology
Abstract/Summary:PDF Full Text Request
Background: endometriosis (endometriosis, EMs), referred to as endometriosis, is acommon and difficult to treat gynecological diseases, the incidence rate of approximately 15% ofwomen of childbearing age, a clear upward trend in recent years. EMs caused by dysmenorrhea,lower abdominal pain, and sexual pain, which seriously affects women's health and quality oflife, is one of the leading major cause of infertility. Currently, EM mainly surgery and thetreatment of hormone-based drugs, but the treatment effect is not ideal, as one of the diseasesdifficult obstetrics and gynecology.The pathogenesis of endometriosis is not fully understood, now widely accepted thatSampson's 1925 endometrial blood reflux planting theory. Reflux of endometrial fragmentssubject to adhesion, invasion and angiogenesis process, in order to form ectopic foci, duringwhich involves a large number of cytokines and endocrine disorders, immune function disorders.In recent years, on the EM eutopic endometrium itself with the characteristics of its role in thepathogenesis gradually attention has been paid.Nuclear factor KappaB (NF-кB) widespread in eukaryotic cells is an important intracellularubiquitous transcription factor, is more than one way to signal to the intersection point of broadparticipation in the immune, inflammatory, and other physiological stress response Pathologicalprocesses. At the same time, NF-кB can efficiently induce a variety of proinflammatorycytokines (IL-1β, TNF-α), RANTES (regulated upon activation normal T cell expressed andsecreted chemokine), etc., at the same time by their transcript regulation, Such as IL-1βcanactivate NF-кB, promoting their more inflammatory transcription factor, creating a positivefeedback loop, the inflammatory response strengthened. Inhibitor of NF-кB prolinedithiocarbamate (PDTC) inhibited NF-кB activity, thus blocking NF-кB way through thebiological effects.PART ONERat model of endometriosisObjective: To study endometriosis provide experimental animal models.Methods: Female SD rats were not pregnant 60, weeks 8 to 10 weeks, weighing 200 ~ 250g,refer to Jones method for cultivation of autologous endometrium. 4 weeks after modeling asecond laparotomy to observe the growth of the endometrium and the cultivation of thehistological changes observed. Graft lesions increase in size, nodular or cystic was transparent, light yellow transparent within the cyst fluid accumulation were as successful model.Results: A total of 60 SD rats do, there are 48 cases of heterotopic transplantation in rats ina transparent small lesions visible cysts, surface vessel formation, most of the ectopic lesionsseen a small cyst can be seen even two. Of which 40 cases of ectopic lesions in rats withperitoneal omentum adhesion, ectopic lesions in 8 patients with intestinal adhesion in rats. SD ratmodel of endometriosis success rate of 80%, 6 cases were not into the rat model, it is estimatedto take endometrial fragments in the area is too small when the endometrium, endometrial andmyometrial plasma separation is not enough relevant, there are 4 cases Mice died of anestheticaccident, and 2 patients died of intra-abdominal abscess.Conclusion: SD rats were transplanted with autologous endometrium in animal modelsbuilt after transplantation of endometrial tissue remains the organization of the originalcharacters, so as to facilitate in-depth study of ectopic foci cell proliferation, angiogenesis,hormone and immune response Other mechanism. This model not only low cost, simpleoperation, short observation period, character and stability, and its spontaneous ovulation for thecycle of animals, higher levels of sex hormones, sexual cycle regularity and cycle faster, thesurvival after transplantation and recurrent endometrial Extremely beneficial change, it is anideal in vivo model of endometriosis.PART TWONuclear factor NF-кB endometriosis in the rat the role of pathogenesisObjective: To investigate PDTC, progesterone and their combination group interventionmodel of endometriosis, the comparative rates of the three rat into a mold, ectopic foci and theNF-кBmRNA, serum TNF-αexpression, of NF-кB the pathogenesis of endometriosis, includingthe role, aimed at the treatment of endometriosis to find new and more effective.Methods: 48 rats modeling success were randomly divided into 4 groups, namely controlgroup, the progesterone group (intraperitoneal injection, 10mg/kg/d, 4 weeks), PDTC group(intraperitoneal injection, 100mg/kg/d, 4 weeks) and PDTC + progesterone group(intraperitoneal injection, the same amount before 4 weeks); in modeling the fourth week andeighth week after the ectopic lesion size measured the size and rate into the mold, with theRt-PCR to detect the Ectopic expression of the NF-κBmRNA and by using enzyme-linkedimmunoassay (enzyme-linked immnunosorbent assay, ELISA) method for measuring serumlevels of TNF-α. ResultResults: 1. Endometriotic lesion growth was observed: the first 4 weeks the control group,PDTC group, progesterone group and PDTC + progesterone group size of a rat model of ectopicfoci were compared, three groups of drugs found in endometriotic lesion volume in theintervention group was significantly lower than the control group, the difference was statisticallysignificant (P<0.05); PDTC group and PDTC + progesterone group was significantly lower thanthe volume of ectopic lesions progesterone group, the difference was significant (P<0.05); PDTC+ Ectopic lesion volume progesterone group than PDTC group, the differences are statisticallysignificant (P<0.05). Thursday, 8 ectopic group size lesion volume compared with the first 4weeks. In the first 8 weeks and 4 ectopic lesions Thursday volume comparison group found thatectopic lesions were the control group gradually increased with time, the difference wasstatistically significant (P<0.05); three groups of drug intervention ectopic focus groups withtime and is gradually reduced, the difference is also statistically significant (P<0.05).2. Detected by ELISA after treatment of serum levels of TNF-αresults are shown: the first4 weeks of serum levels of TNF-αcompared three groups of drug intervention group found thatserum TNF-αin Significantly lower than the control group, the difference was statisticallysignificant (P<0.05); PDTC group and PDTC + progesterone serum levels of TNF-αwassignificantly lower than the progesterone group, the difference was statistically significant (P<0.05); PDTC + progesterone serum levels of TNF-αin the lower PDTC group, the differencesare statistically significant (P<0.05). 8 Thursday of serum levels of TNF-αcompared with thefirst 4 weeks. In the first 8 weeks and 4 Wednesday group of drugs in the intervention group,serum levels of TNF-αfound when comparing the former than the latter and with time graduallydecreased, the differences are statistically significant (P<0.05).3. RT-PCR detected lesions in the rat ectopic expression of NF-кBmRNA results areshown: the first 4 weeks in the rat model of endometriosis, three groups of rats, drug interventionin the NF-кBmRNA ectopic foci was significantly weaker than The control group, the differencewas statistically significant (P<0.05). PDTC group and PDTC + progesterone group in theNF-кBmRNA ectopic foci was significantly weaker than the progesterone group, the differencewas statistically significant (P<0.05). PDTC + progesterone group ectopic foci weaker than theexpression of NF-кBmRNA PDTC group, the difference was statistically significant (P<0.05). 8weeks ectopic foci in rats the expression of NF-кBmRNA, with the first 4 weeks. Will for thefirst 8 weeks and 4 drug intervention group Wednesday ectopic foci in rats the expression ofNF-кBmRNA comparison, the former was weaker than the latter, the difference was statisticallysignificant (P<0.05)Conclusion: (1) NF-кB inhibitor PDTC intervention model of endometriosis in rats, cansignificantly reduce the mold into the ectopic lesions atrophy in rats clear the level of TNF-α expression and NF-κBmRNA significantly lower.(2) NF-кB inhibitor PDTC treated rat model ofendometriosis and effective, and the results are obvious.(3) further confirmed that NF-кB notonly involved in the development of endometriosis and the pathogenesis of endometriosis playsan important role.
Keywords/Search Tags:endometriosis, animal model, SD rats, autotransplantation, NF-κB inhibitor, PDTC, rat, treatment
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