本文選題：尼克酰胺　切入點：內毒素血癥　出處：《重慶醫(yī)科大學》2014年碩士論文　論文類型：學位論文

【摘要】：目的：通過研究證實尼克酰胺（NAM）在小鼠內毒素血癥及膿毒癥模型中的治療作用，為臨床治療膿毒癥提供新的策略。方法：腹腔注射脂多糖（10ug/kg）聯(lián)合半乳糖胺（700mg/kg）（LPS/D-Gal）建立小鼠內毒素所致肝損傷模型，腹腔注射致死劑量脂多糖（20mg/kg）建立內毒素血癥模型，盲腸結扎穿孔（CLP）建立多種微生物感染的小鼠膿毒癥模型。LPS/D-Gal誘導的肝損傷模型中，分別于建模前30min腹腔注射不同劑量的NAM（100mg/kg，200mg/kg，400mg/kg）或建模后1h、3h、6h腹腔注射NAM（400mg/kg），觀察小鼠的存活情況并作生存曲線。于建模后6h，麻醉小鼠，摘眼球取血，檢測血清中轉氨酶水平，一并取肝組織，半胱氨酸天冬氨酸蛋白酶（Caspase）活性檢測及TUNEL檢測觀察肝細胞凋亡，肝組織病理切片觀察形態(tài)學改變；于建模后1.5h取血檢測血清炎癥因子TNF-α水平。致死性內毒素血癥模型中，建模前30min或建模后1h給予NAM（400mg/kg，i.p.），觀察小鼠存活情況并作生存曲線。建模后3h取血，測血清TNF-α、IL-6水平，建模后12h同樣方法取血，測血清ALT及BUN水平，并取肺組織，測肺干濕重比，肺組織病理切片用于觀察形態(tài)學改變。CLP模型中，于手術后1h給予NAM（400mg/kg，i.p.），觀察小鼠存活情況并作生存曲線。結果：在LPS/D-Gal誘導的肝損傷模型中，NAM顯著降低血清轉氨酶水平，并減輕肝組織損傷。NAM還降低腫瘤壞死因子TNF-α水平。通過TUNEL染色試驗及半胱氨酸天冬氨酸蛋白酶（Caspase）活性檢測，證實NAM可以減少肝細胞凋亡。此外，生存分析顯示NAM可降低LPS/D-Gal誘導小鼠的死亡率。在致死性內毒素血癥中， NAM降低血清促炎因子水平及多器官功能損傷，，降低肺組織干濕重比，減輕血清轉氨酶水平及血尿素氮水平。生存分析中，NAM提高了致死性內毒素血癥及CLP膿毒癥小鼠的存活率。結論：研究證實，NAM減輕炎性損傷并提高小鼠存活率，對膿毒癥小鼠可能發(fā)揮治療作用。
[Abstract]:Objective: to investigate the therapeutic effect of nicotinamide (NAM) on endotoxemia and sepsis in mice. Methods: lipopolysaccharide (LPS) and galactosamine (700 mg / kg) were injected intraperitoneally to establish lipopolysaccharide induced liver injury model in mice, and lipopolysaccharide (LPS) 20 mg / kg intraperitoneal injection was used to establish endotoxemia model. Cecal ligation and perforation (CLP) was used to establish the sepsis model of mice infected by various microbes. LPS- D-Gal induced liver injury model. At 30 minutes before modeling, different doses of NAMN 100 mg / kg were injected intraperitoneally with 200 mg / kg of NAMN (400 mg / kg), or 1 hour after modeling, 400 mg / kg NAMN was injected intraperitoneally for 6 h after modeling. The survival of the mice was observed and the survival curve was made. At 6 h after modeling, the anesthetized mice were anesthetized, the blood was taken from eyeball, the level of serum aminotransferase was detected, and the liver tissue was taken. The activity of cysteine aspartate proteinase (caspase) and the detection of TUNEL were used to observe the apoptosis of hepatocytes, the pathological sections of liver were observed for morphological changes, the serum levels of inflammatory factor TNF- 偽 were measured at 1.5 h after modeling, and the levels of TNF- 偽 were detected in the model of fatal endotoxemia. 30 minutes before modeling or 1 hour after modeling, the survival of mice was observed and the survival curve was made. Blood samples were taken at 3 hours after modeling, serum TNF- 偽 IL-6 levels were measured, serum ALT and BUN levels were measured at 12 hours after modeling, lung tissue was taken and lung dry-wet weight ratio was measured. Lung histopathological sections were used to observe the morphological changes in the model of LPS/D-Gal. The rats were treated with NAMN 400 mg / kg i.p. at 1 h after operation. Results: in the model of liver injury induced by LPS/D-Gal, NAM significantly decreased the level of serum aminotransferase. NAM also reduced the level of TNF- 偽 in liver tissue. By TUNEL staining and caspase activity assay, it was proved that NAM could reduce the apoptosis of hepatocytes. Survival analysis showed that NAM could reduce the mortality of mice induced by LPS/D-Gal. In fatal endotoxemia, NAM decreased the level of serum pro-inflammatory factor and the damage of multi-organ function, and decreased the ratio of dry to wet weight of lung tissue. In survival analysis, nam increased the survival rate of mice with fatal endotoxemia and CLP sepsis. It may play a therapeutic role in sepsis mice.
【學位授予單位】：重慶醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R459.7

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