【摘要】 目的 探討NF-κB在重癥急性胰腺炎小鼠腸黏膜屏障功能損傷中的調(diào)控機(jī)制。 方法 36只BALB/C小鼠隨機(jī)分為對(duì)照組、模型組、NF-κB干預(yù)組，每組12只。18 h后處死小鼠，比較各組的腹腔內(nèi)大體改變、腸黏膜病理改變，腸道通透性的變化及血清細(xì)胞因子水平，腸上皮緊密連接蛋白o(hù)ccludin的表達(dá)。 結(jié)果 模型組小鼠腹腔內(nèi)呈明顯炎癥反應(yīng)，腸管水腫，腸黏膜水腫，腸道通透性顯著增高，NF-κB特異性阻斷劑能降低腸道損傷，改善腸黏膜水腫，上調(diào)腸上皮緊密連接蛋白o(hù)ccludin的表達(dá)，顯著降低腸道通透性，降低細(xì)胞因子水平。 結(jié)論 NF-κB阻斷劑能夠通過(guò)選擇性的抑制NF-κB活性，改善受損的腸屏障功能。這一作用通過(guò)上調(diào)腸上皮緊密連接蛋白o(hù)ccludin的水平而實(shí)現(xiàn)。
【Abstract】 Objective To investigate the roles of NF-κB in the intestinal mucosal barrier injury in mice with severe acute pancreatitis(SAP). Methods Thirty-six BALB/C mice were randomly assigned to normal control group, SAP model group and intervention group. Eighteen hours later, pathological intestinal villus changes, intestinal permeability, serum cytokines were evaluated in all three groups. Results In SAP model group, intestinal mucosa was found to be oedematous and intestinal permeability was markedly increased. NF-κB could ameliorate intestinal injury and mucosa edema, and improve intestinal permeability by upregulating occluding expression. Conclusion NF-κB could protect the function of intestinal mucosal barrier by inhibiting NF-κB activity, which suggests that NF-κB may play an intermediating role in SAP-induced intestinal failure through upregulating occluding expression.
引用本文： 張宇飛,嵇武,丁凱,楊榮,范銘興,劉興東,李秋榮. NF-κB在重癥急性胰腺炎小鼠腸黏膜屏障損傷中的作用. 華西醫(yī)學(xué), 2010, 25(8): 1429-1432. doi: 復(fù)制
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| 10. | Wu X, Yu M, Li A. Protective effect of a nuclear factor-kappaB inhibitor on ischemia-reperfusion injury in a rat epigastric flap model[J]. J Reconstr Microsurg, 2008, 24(5): 351-359. |
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- 1. 黎介壽. 腸衰竭－概念、營(yíng)養(yǎng)支持與腸黏膜屏障維護(hù)[J]. 腸內(nèi)與腸外營(yíng)養(yǎng), 2004, 11(2): 65-67.
- 2. Talukdar R, Vege SS. Recent developments in acute pancreatitis[J]. Clin Gastroenterol Hepatol, 2009, 7(11 Suppl): 3-9.
- 3. Rahman SH, Ammori BJ, Holmfield J, et al. Intestinal hypoperfusion contributes to gut barrier failure in severe acute pancreatitis[J]. J Gastrointest Surg, 2003, 7(1): 26-35.
- 4. Harhaj NS, Antonetti DA. Regulation of tight junction and loss of barrier function in pathophysiology[J]. Int Biochem Cell Biol, 2004, 36(7): 1206-1237.
- 5. Frster C. Tight junctions and the modulation of barrier function in disease[J]. Histochem Cell Biol, 2008, 130(1): 55-70.
- 6. Forster C, Silwedel C, Golenhofen N, et al. Occludin as direct target for glucocorticoid-induced improvement of blood-brain barrier properties in a murine in vitro system[J]. J Physiol, 2005, 565(2): 475-486.
- 7. Feldman GJ, Mullin JM, Ryan MP. Occludin: structure, function and regulation[J]. Advanced Drug Delivery Review, 2005, 57: 883-917.
- 8. Cook D, Pisetsky DS, Schwartz DA. Toll-like receptors in the pathogenesis of human disease[J]. Nature Immunology, 2004, 5(10): 975-979.
- 9. Dauphinee SM, Karsan A. Lipopolysaccharide signaling in endothelial cells[J]. Lab Invest, 2006, 86(1): 9-22.
- 10. Wu X, Yu M, Li A. Protective effect of a nuclear factor-kappaB inhibitor on ischemia-reperfusion injury in a rat epigastric flap model[J]. J Reconstr Microsurg, 2008, 24(5): 351-359.
- 11. Inoue S, Nakase H, Matsuura M, et al. The effect of proteasome inhibitor MG132 on experimental inflammatory bowel disease[J]. Clin Exp Immunol, 2009, 156(1): 172-182.