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A Study Of An Animal Model Of Multiple Organ Dysfunction Induced By Partial Ischemia/Reperfusion Of Intestine And Its Pathogenesis

Posted on:2005-06-11Degree:DoctorType:Dissertation
Country:ChinaCandidate:W H CaoFull Text:PDF
GTID:1104360122992036Subject:Surgery - Burn Surgery
Abstract/Summary:PDF Full Text Request
This paper presents a study on an animal model of multiple organ dysfunction induced by partial ischemia and reperfusion (I/R) injury of the intestine, which is more consistent with clinical scenery. The mechanisms of multiple organ dysfunction induced by partial I/R injury of intestine were also discussed. The study included two parts: In the first part, an rabbit model of hemorrhagic shock was produced, and the changes in superior mesentery artery(SMA) blood flow was measured with laser Doppler blood flow meter. Then, according to the changes in SMA blood flow during hemorrhagic shock, the SMA were partially blocked (70% or 50%, lasting for 4 hours or 6 hours) with self -designed instrument in order to replicate an animal model of multiple organ dysfunction induced by partial I/R injury, and the changes in functions and pathology of heart, liver ,kidney and intestine were observed. The results showed that the SMA blood flow was reduced dramatically in hemorrhagic shock. Neither the animal models with SMA occluded by 70%(lasting for 4 hours or 6 hours) nor the animal models with SMA occluded by 50%(lasting for 6 hours) could be used to investigate the multiple organ dysfunction induced by intestine partial I/R injury because of high mortality. Therefore, the model with SMA occluded by 50%(lasting for 4 hours) was used for this study for the desired mortality and the incidence of multiple organs dysfunction induced by partial I/R injury of intestine. The results also suggested that partial I/R injury (SMA blocked to 50%, lasting for 4 hours) could produce multiple organ dysfunction and significant pathological injuries in different organs.In the second part, on basis of the successful replication of animal models of multiple organ dysfunction induced partial I/R injury of intestine, its pathogenesis were discussed. The effects of carbachol, which was injected into duodenum, on partial I/R injury of intestine were observed. Eighty white rabbits were divided into four groups: partial I/R of intestine, carbachol treatment, sham operation, normal control. In partial I/R of intestine and carbachol treatment groups, the SMA were occluded by 50% for 4 hours, then the rabbits were given fluid resuscitation. In carbachol treatment group, carbacholpμg/ml) in the dose of 2.5μg/kg was injected into the duodenum 1 hour after the SMA occlusion. Except for the normal control group, all the animals were given intravenous nutrition(100Kcal/kg.d). The plasma and peripheral blood lymphocytes, PMN were separated from arterial blood at 2h, 4h, 6h, 8h, 1d, 2d, 3d after the SMA occlusion. The changes in TNF-alpha ,IL-6,IL-10,MDA , the ratio of apoptosis and capase-3 ofperipheral blood lymphocytes and PMN were measured. The changes of functions and pathology heart, liver, kidney, spleen, intestine lymph node and intestine were observed. The proliferation ability of peripheral blood lymphocytes, spleen cells, intestine lymph node cells by stimulation with PHA was measured, and the changes in apoptosis and caspase-3 of spleen cells, and intestine lymph node cells were also observed. Meanwhile, the portal vein blood, lung, spleen and intestine lymph node were cultured to investigate the bacterial translocation.The results showed that partial I/R injury of intestine cause the excessive excretion of TNF-alpha ,IL-6 and the suppression of IL-10 secretion. In the intestine ischemia stage, The apoptosis of peripheral blood PMN and lymphocytes and the expression of caspase-3 were increased dramatically; After intestine reperfusion, the apoptosis of peripheral blood PMN and lymphocytes and the expression of caspase-3 were decreased sharply, the proliferation ability of peripheral blood lymphocytes, spleen cells, intestine lymph node cells was decreased . Carbachol could dramatically increase the blood flow of intestine mucosa, ameliorated the paralysis, decreased the production of TNF-alpha , IL-6, MDA, promoted the apoptosis of PMN, increase the proliferation ability of peripheral blood lymphocytes, spleen cells, intestine lymph no...
Keywords/Search Tags:Ischemia/Reperfusion
PDF Full Text Request
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