【摘要】： 研究目的探討核因子-κB(NF-κB)信號途徑在大鼠內(nèi)毒素血癥中的作用,為臨床尋求以NF-κB為靶點的治療手段提供實驗依據(jù)。 研究方法采用尾靜脈注射內(nèi)毒素制作成年SD大鼠的內(nèi)毒素血癥(急性炎癥綜合征)模型,通過檢測肝功能和HE染色組織學檢查證實造模成功,用組織化學方法檢測肝臟,脾臟NF-κB P65活化的表達水平。隨機分組,用抗氧化劑PDTC三個不同劑量處理,考察對NF-κB P65和TNF-α表達的影響。數(shù)據(jù)用SPSS13.0軟件處理,分析。 研究結(jié)果內(nèi)毒素血癥大鼠脾臟NF-κB P65活化陽性在內(nèi)毒素刺激后1 h表達,細胞核內(nèi)P65陽性細胞數(shù)(24.75±4.3)即明顯增加:3 h陽性細胞數(shù)(116.5±12.2)增加達高峰(P＜0.01):3h后逐漸減少,到24 h時陽性細胞數(shù)明顯減少(41.25±10.2),而且已經(jīng)與對照組比較差異無統(tǒng)計學顯著性。應用PDTC 50～200 mg/kg對肝臟,脾臟NF-κB P65活化陽性表達均有抑制作用,而且量效關(guān)系明顯。應用PDTC 200 mg/kg,對NF-κB活性抑制作用最強,對TNF-α活化陽性表達抑制作用也最強,并能有效降低轉(zhuǎn)氨酶水平,對肝臟有保護作用。 結(jié)論大鼠內(nèi)毒素血癥時肝臟,脾臟NF-κB和TNF-α均有明顯激活,抗氧化劑PDTC能抑制內(nèi)毒素血癥大鼠肝臟,脾臟NF-κB及TNF-α活化,且存在量—效依賴關(guān)系,并能降低轉(zhuǎn)氨酶水平,減輕肝損傷。
[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- 偽 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 鹵4. 3), and the number of positive cells in 3 h (116.5 鹵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 鹵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- 偽, and could effectively reduce the level of transaminase and protect the liver. Conclusion NF- 魏 B and TNF- 偽 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- 偽 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.
【學位授予單位】：中南大學
【學位級別】：碩士
【學位授予年份】：2009
【分類號】：R363

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