PDTC对大鼠内毒素血症肝损伤保护机制的研究

发布时间：2018-12-10 12:45

【摘要】： 研究目的探讨核因子-κB(NF-κB)信号途径在大鼠内毒素血症中的作用,为临床寻求以NF-κB为靶点的治疗手段提供实验依据。研究方法采用尾静脉注射内毒素制作成年SD大鼠的内毒素血症(急性炎症综合征)模型,通过检测肝功能和HE染色组织学检查证实造模成功,用组织化学方法检测肝脏,脾脏NF-κB P65活化的表达水平。随机分组,用抗氧化剂PDTC三个不同剂量处理,考察对NF-κB P65和TNF-α表达的影响。数据用SPSS13.0软件处理,分析。研究结果内毒素血症大鼠脾脏NF-κB P65活化阳性在内毒素刺激后1 h表达,细胞核内P65阳性细胞数(24.75±4.3)即明显增加:3 h阳性细胞数(116.5±12.2)增加达高峰(P＜0.01):3h后逐渐减少,到24 h时阳性细胞数明显减少(41.25±10.2),而且已经与对照组比较差异无统计学显著性。应用PDTC 50～200 mg/kg对肝脏,脾脏NF-κB P65活化阳性表达均有抑制作用,而且量效关系明显。应用PDTC 200 mg/kg,对NF-κB活性抑制作用最强,对TNF-α活化阳性表达抑制作用也最强,并能有效降低转氨酶水平,对肝脏有保护作用。结论大鼠内毒素血症时肝脏,脾脏NF-κB和TNF-α均有明显激活,抗氧化剂PDTC能抑制内毒素血症大鼠肝脏,脾脏NF-κB及TNF-α活化,且存在量—效依赖关系,并能降低转氨酶水平,减轻肝损伤。
[Abstract]:Objective to investigate the role of nuclear factor- 魏 B (NF- 魏 B) signaling pathway in rat endotoxemia, and to provide experimental evidence for clinical treatment targeting NF- 魏 B. Methods the endotoxemia (acute inflammatory syndrome) model of adult SD rats was established by injecting endotoxin into tail vein. The liver function and HE staining histologic examination proved that the model was successful, and the liver was detected by histochemical method. The expression of NF- 魏 B p65 in spleen. The effects of three different doses of antioxidant PDTC on the expression of NF- 魏 B p65 and TNF- 伪 were studied. The data is processed and analyzed by SPSS13.0 software. Results the positive expression of NF- 魏 B p65 in spleen of endotoxemia rats was 1 h after endotoxin stimulation. The number of p65 positive cells in the nucleus increased significantly (24.75 卤4. 3), and the number of positive cells in 3 h (116.5 卤12. 2) increased to the peak (P < 0. 01): after 3 hours, the number of positive cells gradually decreased. At 24 h, the number of positive cells decreased significantly (41.25 卤10.2), and there was no significant difference compared with the control group. The positive expression of NF- 魏 B p65 in liver and spleen was inhibited by PDTC 50 ~ (200 mg/kg), and the dose-effect relationship was significant. PDTC 200 mg/kg, had the strongest inhibitory effect on the activity of NF- 魏 B and the strongest inhibition on the positive expression of TNF- 伪, and could effectively reduce the level of transaminase and protect the liver. Conclusion NF- 魏 B and TNF- 伪 in the liver and spleen of rats with endotoxemia were significantly activated. The antioxidant PDTC could inhibit the activation of NF- 魏 B and TNF- 伪 in the liver, spleen and spleen of rats with endotoxemia, and had a dose-effect relationship. It can reduce the level of transaminase and alleviate liver injury.
【学位授予单位】：中南大学
【学位级别】：硕士
【学位授予年份】：2009
【分类号】：R363

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