雌激素对胰岛移植的保护作用及其机制研究微生物学专业论文.docxVIP

AbstractNDstract Abstract NDstract Pancreatic islet transplantation(PIT)is currently the most physiological treatment for type l diabetes，while its clinical application is largely hindered due to the shortage of islet availability(the recipients usually need islets from 1-2 donors and 1-3 times PIT to achieve insulin independent)，and great b-cell loss after PIT．．We and others have previously shown that estrogen(E2)can protect mouse and human islet survival from various injuries．E2 promotes pancreatic 13 cell survival and insulin biosynthesis via non-genomic and extracellular estrogen receptor(ER)signaling． 0BJEOT I VE-一To optimized the dose and time of E2 application in protecting PIT， and to explore the mechanism of E2 protection of PIT． RES队RCH DES I GN AND METHOD孓一Diabetes was induced in 8 to 1 0-week．old male C57BL／6 mice by a single i．p．injection of l 80 mg／kg streptozotocin，Blood glucose was monitored with One Touch Ultra Glucose Monitor．Mice with fed blood glucose exceeding 1 6．7 mmol／1 were used as recipients．Islets were isolated from normal C5 7BL／6 mice．A marginal dose of islets were transplanted under the kidney capsule of recipient mice．For in vivo treatment，E2 were subcutaneously injected from the day of PIT surgery．Dose-response and time-course stud ies were performed individually to optimize the application dose and time of E2 application to eliminate it potential side effects．After that，E2 was used at optimized dose and duration in PIT, and the kidney harbored islet grafts were retrieved on day 3，7，and 1 4 after PIT．Islet survival and revascularization was measured by quantification of insulin and endothelial cell marker IB4 expression via|mmunohistochemical staining．Endothelia nitricoxide synthase(eNOS)inhibitor L-NAME was applied to investigate the effect of eNOS signaling．the critical signaling pathway in endothelia function and survival， in E2 protection of PIT． RESULTS--E2 exerted a persistent protection on PIT when administered at the dose 万方数