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

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

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200～220g，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、0．45mg／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150μg，NS组给予等容量生理盐水。分别于注射戊乙奎醚后4、6和12h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（P〉0．05），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、0．45mg／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。

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-regnlation of expression of NF-κB and iNOS.