目的 探討性別差異對內(nèi)毒素血癥大鼠肺臟組織核因子-κB(NF-κB)活化的影響。
方法 取40只清潔級Wistar大鼠,雌、雄各半,分為對照組(雌、雄各10只)和內(nèi)毒素血癥組(雌、雄各10只),采用腹腔注射內(nèi)毒素5 mg/kg制作動物模型,無菌留取肺臟組織標(biāo)本,用凝膠阻滯遷移分析方法(EMSA)檢測NF-κB的活化情況,同時檢測大鼠血清中腫瘤壞死因子-α(TNF-α)及雌二醇(E2)含量。
結(jié)果 對照組雌、雄性大鼠肺臟組織有NF-κB微弱活化,分別為1.33±0.24和1.47±0.40,同時血清中TNF-α含量較少,分別為(0.75±0.16) ng/ml和(0.82±0.12) ng/ml,各項指標(biāo)在雌、雄性大鼠間差異無統(tǒng)計學(xué)意義(P>0.05); 注射內(nèi)毒素后雌、雄性大鼠的NF-κB值分別為12.10±2.89和19.53±2.12,TNF-α值分別為(4.10±0.72) ng/ml和(6.37±1.29) ng/ml,較對照組明顯升高(P<0.01),但是雌性大鼠各項指標(biāo)的變化明顯低于雄性大鼠(P<0.01)。對照組雌、雄性大鼠血清E2水平分別為(5.94±1.03) ng/L和(0.93±0.30) ng/L,注射內(nèi)毒素后相應(yīng)值為(6.13±1.31) ng/L和(1.06±0.26) ng/L,但兩組間差異無統(tǒng)計學(xué)意義(P gt;0.05)。
相關(guān)分析表明,雌、雄性內(nèi)毒素血癥大鼠肺臟組織NF-κB 的活化與血清中TNF-α含量呈正相關(guān)(r=0.921 1,P=0.013; r=0.907 2,P=0.017),與E2含量呈負相關(guān)(r=-0.887 5,P=0.017; r=-0.872 3,P=0.022)。
結(jié)論 內(nèi)毒素血癥大鼠肺臟組織NF-κB的活化及血清中TNF-α的含量存在性別差異,內(nèi)源性雌激素可能通過抑制NF-κB 的活化介導(dǎo)了對雌性內(nèi)毒素血癥大鼠肺臟的保護作用。
引用本文: 杜曉輝,李榮,徐迎新,姚詠明,申傳安,尹會男. 性別差異對內(nèi)毒素血癥大鼠肺臟組織核因子-κB活化的影響. 中國普外基礎(chǔ)與臨床雜志, 2007, 14(1): 53-55. doi: 復(fù)制
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- 3. Schroder J, Kahlke V, Staubach KH, et al. Gender differences in human sepsis [J]. Arch Surg, 1998; 133(11)∶1200.
- 4. Yang H, Young DW, Gusovsky F, et al. Cellular events mediated by lipopolysaccharide-stimulated toll-like receptor 4. MD-2 is required for activation of mitogen-activated protein kinases and Elk-1 [J]. J Biol Chem, 2000; 275(27)∶20861.
- 5. Knoferl MW, Diodato MD, Angele MK, et al. Do female sex steroids adversely or beneficially affect the depressed immune responses in males after trauma-hemorrhage? [J]. Arch Surg, 2000; 135(4)∶425.
- 6. Gould IM, MacKenzie FM. The response of Enterobacteriaceae to beta-lactam antibiotics——‘round forms, filaments and the root of all evil’ [J]. J Antimicrob Chemother, 1997; 40(4)∶495.
- 7. Bone RC, Balk RA, Fein AM, et al. A second large controlled clinical study of E5, a monoclonal antibody to endotoxin: results of a prospective, multicenter, randomized, controlled trial. The E5 Sepsis Study Group [J]. Crit Care Med, 1995; 23(6)∶994.
- 8. Hassouna H, Quinn C. Proteolysis of protein C in pooled normal plasma and purified protein C by activated protein C (APC) [J]. Biophys Chem, 2002; 95(2)∶109.
- 9. Mitteregger R, White A, Weber C, et al. In vitro cell culture systems as the basis for an extracorporeal blood purification strategy in multiorgan failure treatment [J]. Ther Apher, 1999; 3(3)∶257.