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The Effects Of Gut Peptides On Intestinal Lymphocyte Homing In Rats With Multiple Organ Dysfunction Syndrome

Posted on:2004-09-11Degree:DoctorType:Dissertation
Country:ChinaCandidate:H YangFull Text:PDF
GTID:1104360092999760Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Multiple organ dysfunction syndrome (MODS) is the most serious result induced by trauma and infection. Once established, MODS defies our supportive measures. Mortality ranges from 40% to 100% and is related directly to the number and duration of organ failures. Unfortunately, neither the incidence nor the mortality of the syndrome has improved significantly. MODS is regarded as a continuous inflammatory response that is unable to be controlled. Intestinal mucosal barrier function disturbance, including intestinal mucosal immune dysfunction, play a vital role during the development of the systemic inflammatory response syndrome which causes important organs or tissues injury and then runs to MODS.The mucosal immune system consists of an integrated network of tissues, including the lymphoid cells in Peyer's pathes and lamina propria, and intraepithelial lymphocytes. Major effector cells include CD4+ T cells, CD8+ T cells, B cells, differentiated plasma cells, macrophages, and antigen-presenting cells (APCs) and so on. Major effector molecules include antibodies, largely of the immunoglobulin A (IgA) isotype as well as cytokines, chemokines, and their receptors. Lymphocytes activated, lymphoid cell homing, and SIgA secrete are taken as the main mucosal immune response.Accumulative studies show that the injury of intestinal mucosa plays a vital role at the beginning and development of MODS. However, the role of intestinal mucosal immune system, as an important part of intestinal mucosa barrier, especially in the case of MODS remains still unclear.Intestinal lymphocyte homing, as one of an important immune activites, conducts the function of immune surveillance and immune cleaning and therefore is involved in the acute and chronic inflammation of intestinal mucosa. It is an important trafficking bridge between intestinal mucosal immune system and systemic immune system. Gut peptides, cell adhesion molecules, and other cytokines have shown an important effect on the migration of lymphocytes. However, the knowledge on the regulation of intestinal mucosal lymphocyte homing in the situation of normal or MODS is still limited.In addition, intestinal mucosa is the place plenty of neurocytes and transmitters, endocrinocyte and polypeptides, immunologically competent cells and cytokines. Gut peptides are important regulators in the neuro-endocrine-immune network. VIP, SST and other peptidergic nerve fibers, which are near various immune cells, are found in intestinal laminal propria and Peyer's patches with high concentration or density. They are capable of regulating the lymphocyte migration here. However, the effects of gut peptides on intestinal lymphocyte homing, especially in the case of MODS remain unclear.AIMSTo investigate:1. The migration behavior of intestinal lymphocyte at gut-associated lymphoid tissue (GALT) in the physical state;2. The regulation of VIP or SST on homing of intestinal lymphocyte at GALT in normal rats;3. The changes of homing of intestianl lymphocyte at GALT in rats with MODS;4. The effects of VIP or SST on homing of intestinal lymphocyte of rats with MODS;5. Whether intestinal circulating lymphocyte expresses mRNA of receptors for SST and VIP;6. The effect of VIP and SST on expression of MAdCAM-1, which exists in high endothelial venules of Peyer's patches and intestinal lamina propria and targets migration of intestinal lymphocyte.METHODS1. Intestinal lymphocyte was collected from rat intestinal lymphatics by a plastic tube.2. The percentage of T lymphocytes in intestine lymph liquid was determined by E rose ring.3. The percentage of CD4+ and CD8+ T lymphocytes in intestine lymph liquid was measured by flow cytometry.4. 51Cr-labeled lymphocyte distributed in GALT was counted with -counter.5. The rat model of MODS was established by intestine isochemia-reperfusion.6. Tumor necrosis factor a (TNF- ) in plasma and intestinal mucosa was determined with a ELISA Kit for TNF- .7. D(-)-Lactate level in plasma was m...
Keywords/Search Tags:multiple organ dysfunction syndrome, mucosal immune system, gut-associated lymphoid tissue, intestinal lymphocyte homing, somatostatin, vasoactive intestinal polypeptide
PDF Full Text Request
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