| BACKGROUND AND OBJECTIVE: Septic shock and multiple organ dysfunction syndrome (MODS) is a major cause of morbidity and mortality in surgical intensive care units. previous therapies for these disorders produced the uniformly negative results; at least two reasons for this condition. First, only blockade certain earlier inflammation agent cannot prevent effectively inflammatory cascade. Second, excessive obstruction of proinflammatory mediator may result in the compensatory anti-inflammatory response syndrome, which can impair the immunological function and increase the opportunity of later secondary infection. Therapies for septic shock and MODS shoud consider how to keep the balance of pro- and anti-inflammatory mediators in the circulation and how to regulate the immunological function. As rat experiment, TNF-α, IL-1, IL-6, IL-10, TGF-β in serum of the acute pancreatitis increased significantly. After treatment with 5-fluoroucil(5-FU), these inflammatory cytokines significantly decreased. Obvious improvement of index of the severity of the acute pancreatitis, including the amylopsin and the wet weight of pancreatic tissue, also were observed after treatment of 5-FU. So the purpose to cure the acute pancreatitis with 5-FU can be achieved through regulating both pro- and anti- inflammatory cytokines,rectifying the abnormal immunity and alleviating the pathophysiological disorders of acute pancreatitis. We do not know whether 5-FU is a protective function in septic shock, and not find the answer about this question. The objective of this experiment is to observe the effect of 5-FU on prognosis of Wistar rat with established septic shock model, and to discuss the mechanism of treatment of septic shock with 5-FU. METHOD: First, twenty female Wistar rats were randomly divided into four groups. Every group rats were injected intraperitonealy with different concentration of cultured E. coli (3.6* 109, 1.8* 109, 0.9* 109 or 0.3><109cfu/ml). Mortality of every group was observed. Second, thirty female Wistar rats were randomly divided into three groups: Group 1. The normal rats as a control; Group 2. Septic shock model were established by peritoneal injection with 1.8><109cfu/ml E. coli at the volume of lml/lOOg weight; Group 3. 40 minutes later after the model were established, the rats were injected intraperitonealy with 5-FU 50mg/kg weight. All rats were killed at 6 hours after operation, and the mortality, the ascites rate, the lung tissue wet weight and the lung injury score(LIS) were observed.RESULTS: 1. Almost all of the death event took place in 6 hours after the operation were performed, and the best concentration of cultured E. coli to establishing the septic shock was 1.8><109cfu/ml. 2. The mortality, the ascites rate, the lung tissue wet weight and LIS of the septic shock group was 60%, 90%, 1.55 ± 0.17g and 8.00. In 5-FU group, these data was respectively became to 0, 10%, 1.36 ± 0.14g and 5.20. So, 5-FU can decrease the mortality and the ascites rate of septic shock. The Obvious improvement of the index of the severity of the septic shock, including the lung tissue wet weight and LIS, also is observed after treatment of 5-FU.CONCLUSION: 1. Septic shock model with cultured E. coli have a virtue of simple operation, easly controlled experiment condition and steady experiment resolute. It's asuitable model for research the role of drug on the degree of inflammatory reaction and the change of immunological function in septic shock. 2. 5-FU can relieve the degree of inflammation reaction and tissue damage, and prevent from death in septic shock. It's protective effect may be achieved through rectifying the excessive activation of immunologic cell and keeping immunologic balance in a lower level. |
PDF Full Text Request