The Experimental Research For The Interrelationship Between Leptin, OB-R,Their Control Elements And Endometriosis

Endometriosis is a gynecologic benign disease with biological behavior ofmalignant tumor, employing the feature of pain, infertility and pelvic mass. Theincidence of the disease rises up recently which affected the life quality seriously, butthe pathogenic mechanism isn’t clear. A great quantity of basic and clinical researchdiscovered that the expression and regulation of leptin and OB-R played an importantrole in the occurrence and progress of endometriosis including vascular neogenesis, cellproliferation and apoptosis, immunological regulation, inflammation reaction andmetabolism. It can provide the new breakthrough point of endometriosis pathogenicstudy, clinical treatment and new drug exploitation by researching on the leptin, OB-R,regularity of the expression and change of its upstream and downstream gene.There are2parts in this study：1.Establish the SCID mice implantation animal model of EMT, to investigateexpression of the relevant factorsTo investigate leptin, OB-R and its upstream and downstream regulation factorsrelated to the characteristics of the endometrium in transplanted tumor tissue and SCIDmice uterus, we established endometriosis subcutaneous xenograft model in SCID mice.Then, observed the expression of factor by immunohistochemistry. EMT can be fullyreflected from the pathophysiological characteristics, the strength of expression andpositioning features of leptin, OB-R, STAT3and p-STAT3is clear, as the follow-upexperiment reference.2. The role of related drugs that affected the expression of leptin, OB-R and STAT3in SCID mice endometriosis lesions.Give the leptin metabolism related drug therapy to the SCID mouse modelintervention, and observe the changes of lesions in mice. Variations were measured byreal-time quantitative polymerase chain reaction and immunohistochemistry, to locaterelevant factors expression characteristics, analyze and validate the therapeutic effectand systemic effects of drugs used for endometriosis.Conclusions are as follows:1) Cyclic adenosine phosphate can inhibit the expression of leptin, but could notinhibit the expression of the downstream OB-R, STAT3and p-STAT3. Thus itplayed a limited role in the treatment of EMT, specific mechanism needs furtherresearch.2) The impact L-carnitine in acute and chronic inflammatory process on leptinmetabolism is different, can’t reduce the expression of leptin、OB-R and STAT3inthe process of chronic inflammation, does not apply to the treatment of EMT.3) Mifepristone can significantly reduce leptin, OB-R and STAT3expression, is aneffective drug for the treatment of EMT, but there is an impact on body weight.4) Inhibition of progesterone on the EMT lesions may not by leptin-OB-R-JAK2/STAT3pathway.5) S3I-201can effectively inhibit the expression of leptin, OB-R, STAT3andabnormal phosphorylation of STAT3, is an expected and effective to become a newEMT treatment.To sum up, this study suggests：1. Leptin is a sensitive index in the process of EMT development, can be used indisease diagnosis, judging curative and relapse, is expected to become the EMTreference monitoring indicators.2. The research on upstream or downstream of leptin、OB-R、their control factors andrelated signaling pathways, is helpful for comprehending the pathogenesis of EMTand the development of new targets for drug treatment.