戊乙奎醚预先给药对大鼠内毒素性脑损伤时NF-κB和iNOS表达的影响

目的 评价戊乙奎醚预先给药对大鼠内毒素性脑损伤时NF-κB和诱导型一氧化氮合酶(iNOS)表达的影响.方法 雄性SD大鼠105只,体重200～220 g,随机分为5组(n=21),D1组、D2组或D3组分别腹腔注射戊乙奎醚0.05、0.15、0.45 mg/kg,NS组和L组给予等容量生理盐水,10min后L组、D1组、D2组和D3组经左颈内动脉注射脂多糖150 μg,NS组给予等容量生理盐水.分别于注射戊乙奎醚后4、6和12 h处死7只大鼠,取脑组织,测定脑组织含水量、NF-κB和iNOS表达水平,光镜和电镜下观察脑组织病理学结果.结果 与NS组相比,L组、D1组、D2组和D3组脑组织含水量、NF-κB和iNOS表达增加(P<0.05);与L组相比,D1组脑组织含水量、NF-κB和iNOS表达差异无统计学意义(P0.05),D2组和D3组脑组织含水量、NF-κB和iNOS表达降低(P<0.05).D2组和D3组脑组织病理学损伤轻于L组.结论 戊乙奎醚0.15、0.45 mg/kg预先给药减轻大鼠内毒素性脑损伤的机制与抑制脑组织NF-κB和iNOS表达上调有关.

Effects of penehyclidine hydrochloride pretreatment on expression of NF-κB and iNOS in brain tissue in rats with LPS-induced brain injury

Objective To investigate the effects of penehyclidine hydrochloride (PHCD) pretreatment on expression of NF-κB and iNOS in rats with LPS-induced brain injury. Methods One hundred and five male SD rats weighing 200-220 g were randomly divided into 5 groups (n=21 each): group Ⅰ normal saline (NS);group Ⅱ LPS (L);group Ⅲ,Ⅳ,Ⅴ PHCD 0.05, 0.15, 0.45 mg/kg (D1,2,3). The animals were anesthetized with chloral hydrate 350 mg/kg. Brain injury was induced by intra-arterial LPS 150 μg administered via left internal carotid artery in group Ⅱ-Ⅴ. In group Ⅲ,Ⅳ, and Ⅴ PHCD 0.05, 0.15 and 0.45 mg/kg were given intraperitoneally (IP) at 10 min before intra-arterial LPS. The animals were decapitated at 4, 6 and 12 h after administration of PHCD (n=7 at each time point in each group). The brains were immediately removed for determination of water content, expression of NF-κB and iNOS protein and examination with light and electron microscope. Results Water content of the brain and expression of NF-κB and iNOS protein were significantly higher in group L, D1, D2 and D3 than in group NS and were significantly lower in group D2 and D3 than in group L. Intra-arterial LPS produced severe damage to the brain which was significantly attenuated by PHCD in group D2 and D3. Conclusion PHCD 0.15,0.45 mg/kg pretreatment can attenuate LPS-induced brain injury by inhibiting the up-regulation of expression of NF-κB and iNOS.