【摘要】： 研究目的探討核因子-κB(NF-κB)信號(hào)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(diǎn)的治療手段提供實(shí)驗(yàn)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(guò)檢測(cè)肝功能和HE染色組織學(xué)檢查證實(shí)造模成功,用組織化學(xué)方法檢測(cè)肝臟,脾臟NF-κB P65活化的表達(dá)水平。隨機(jī)分組,用抗氧化劑PDTC三個(gè)不同劑量處理,考察對(duì)NF-κB P65和TNF-α表達(dá)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(yáng)性在內(nèi)毒素刺激后1 h表達(dá),細(xì)胞核內(nèi)P65陽(yáng)性細(xì)胞數(shù)(24.75±4.3)即明顯增加:3 h陽(yáng)性細(xì)胞數(shù)(116.5±12.2)增加達(dá)高峰(P＜0.01):3h后逐漸減少,到24 h時(shí)陽(yáng)性細(xì)胞數(shù)明顯減少(41.25±10.2),而且已經(jīng)與對(duì)照組比較差異無(wú)統(tǒng)計(jì)學(xué)顯著性。應(yīng)用PDTC 50～200 mg/kg對(duì)肝臟,脾臟NF-κB P65活化陽(yáng)性表達(dá)均有抑制作用,而且量效關(guān)系明顯。應(yīng)用PDTC 200 mg/kg,對(duì)NF-κB活性抑制作用最強(qiáng),對(duì)TNF-α活化陽(yáng)性表達(dá)抑制作用也最強(qiáng),并能有效降低轉(zhuǎn)氨酶水平,對(duì)肝臟有保護(hù)作用。 結(jié)論大鼠內(nèi)毒素血癥時(shí)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(xué)位授予單位】：中南大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2009
【分類號(hào)】：R363

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