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The Study On Relationship Between Nitric Oxide And Gut Barrier Dysfunction In Rats Induced By The Chemotherapy Of 5-Flurouracil Introperitoneally

Posted on:2005-04-13Degree:MasterType:Thesis
Country:ChinaCandidate:J Y SunFull Text:PDF
GTID:2144360125958424Subject:Surgery
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Objective: The research of nitric oxide (NO) is one of the popularest subjects in life science fields recently. Many studies have showed that NO has close relations with tumor, trauma, infection and the diseases in circulatory, gastroenteritic, immune system. NO exists in many tissues and it may have different effect in different parts of organ/tissue. It is reported that on gastrointestinal tract NO may have protective effect, on the other hand, it may have damage effect. Thus, NO plays dual role in gastrointestinal tract. 5-Fluorouracil chemotherapy is often accompanied by gastrointestinal toxicity, it often causes gut barrier dysfunction and bacterial translocation. In our study, the gut barrier dysfunction and bacterial translocation in rats induced by the chemotherapy of 5-flurouracil was observed, the NO level, nitric oxide synthase(NOS) and its isoforms i.e. inducible nitric oxide synthasewas(iNOS) and constitutive nitric oxide synthase (cNOS) activity were detected in ileum and colon tissues. The aim is to study the relationship between NO and gut barrier dysfunction in rats induced by the chemotherapy of 5-Flurouracil introperitoneally and explore a new protective method in the future. Methods: Thirty Wister rats were randomly divided into three groups: control,(C) model,(M) and treatment.(T) Ten rats were put into each group. During the experiment, Both the group M and the group T received 5-Fu 100mg/kg injection introperitoneally on the fourth day respectively, to make the model of gut barrier injury, whereas the rats in group T were given Smectite powder 100mg/kg intragastric administration before the administration of 5-Fu and continued for three days. At the same time, the group C received the same dose of saline solution injection introperitoneally. The contents of endotoxin in peripheral blood were measured in all groups after rats killed on the seventh day. The mesenteric lymph nodes (MLN) were harvested for comparing bacterial translocation incidence among three groups. Ileum and colon tissue were taken for pathologic examination including comparing mucosal thickness, villus height of ileum and morphology change. The level of NO and NOS( including iNOS and cNOS) activity in ileum and colon tissue were measured by spectrophotometry respectively. Statistical Analysis System 6.12 (SAS6.12)was used for data statistical analysis. one-way analysis of variance and SNK-q test were used for quantitative data analysis, Chis-quare test and a Fisher exact test were used for qualitative data. P values that were less than 0.05 were considered statistical significance. P values that were less than 0.01 were considered remarkable statistical significance. Results: ① Both the contents of endotoxin in peripheral blood in group M (0.101±0.012 Eu/ml)and group T(0.066±0.006 Eu/ml), which 5-Fu were administrated, were significantly higher than that of group C(0.042±0.003Eu/ml), (P<0.01) the level of endotoxin in group T was significantly lower than that of group M. (P<0.01) ②Three positive cases of bacterial translocation of MLN were only found in group M (3/10), there was no bacterial translocation of MLN in group C and group T;No positive culture case of bacteria translocation of liver tissue was found in three groups. ③The levels of NO in ileum and colon tissue in group M (ileum: 3.18±0.21 umol/gprot, colon: 2.64±0.24 umol/gprot) and group T( ileum: 1.79±0.23 umol/gprot, colon: 1.74±0.30 umol/gprot) were significant higher than that of group C,( ileum: 1.45±0.13 umol/gprot,colon: 1.40±0.19 umol/gprot) respectively. (P<0.01) The content of NO in group T was significantly lower than that of group M.(P<0.05). The iNOS activity in ileum and colon tissue in group M (ileum: 1.66±0.25U/mgprot,colon: 1.54±0.21U/mgprot) and group T(ileum: 1.46±0.24U/mgprot, co1on: 1.33±0.23U/mgprot) were significantly higher than that of group C,(ileum: 0.47±0.11U/mgprot, colon: 0.47±0.08U/mgprot) respectively.(p<0.01) The iNOS activity in group T was lower than that of in group M.(P<0.05)...
Keywords/Search Tags:Gut barrier dysfunction, Bacterial translocation, Chemotherapy, Nitric oxide, Nitric Oxide Synthase, Inducible Nitric Oxide Synthase
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