盐酸戊乙奎醚预先给药对内毒素性急性肺损伤大鼠肺组织CD14和Toll样受体4表达的影响

Effect of penehyclidine hydrochloride pretreatment on CD14 and Toll-like receptor 4 expression in lung tissues in rats with acute lung injury induced by lipopolysaccharides

目的探讨盐酸戊乙奎醚预先给药对内毒素性急性肺损伤大鼠肺组织CD14和T0u样受体4（TLR4）表达的影响。方法健康雄性sD大鼠32只，2月龄，体重230～280g，采用随机数字表法，将大鼠随机分为4组（n=8），对照组（c组）：腹腔和尾静脉均注射生理盐水1ml／kg；急性肺损伤组（ALI组）：腹腔注射生理盐水1ml／kg，30min后经尾静脉注射内毒素5mg／kg；盐酸戊乙奎醚低剂量组（IJP组）和高剂量组（HP组）：分别腹腔注射盐酸戊乙奎醚0．3和1．0mg／kg，30min后经尾静脉注射内毒素5mg／kg。静脉注射生理盐水或内毒素后6h时，取肺组织，分别采用Western blot法和RT—PCR法检测CD14、TLR4蛋白及其mRNA的表达水平，并观察肺组织病理学结果。结果与c组比较，Au组、LP组和HP组肺组织CD14、TLR4蛋白及其mRNA表达上调（P〈0．05）；与Au组比较，LP组及HP组肺组织CD14、TLR4蛋白及其mRNA表达下调（P〈0．05）。LP组和HP组CD14、TLR4蛋白及其mRNA表达差异无统计学意义（P〉0．05）。LP组和HP组肺组织病理学损伤较ALI组减轻。结论盐酸戊乙奎醚预先给药可通过降低肺组织CD14、TLR4的活性减轻大鼠内毒素性急性肺损伤。

Objective To investigate the effects of penehyclidine hydrochloride （PHCD） pretreatment on CD14 and Toll-like receptor 4（TLR4）expression in lung tissues in rats with acute lung injury（ALI） induced by li- popolysaccharides （LPS）. Methods Thirty-two healthy male SD rats aged 2 months weighing 230-280 g were ran- domly divided to 4 groups （n = 8 each）： control group（group C）, ALI group,low dose PHCD group（group LP） and high dose PHCD group（group HP）. ALI was induced by intravenous LPS 5 mg/kg via tail vein. Groups LP and HP received intraperitoneal PHCD 0.3 and 1.0 mg/kg respectively 30 min before LPS administration. The rats were sacrificed at 6 h after LPS administration. The lungs were removed immediately for microscopic examination and determination of the mRNA and protein expression of CD14, TLR4 by RT-PCR and Western blot. Results The CD14,TLR4 protein and mRNA expression was significantly higher in groups ALI, LP and HP than in group C, and lower in groups LP and HP than in group ALI（ P 〈 0.05）. There was no significantly difference in CD14, TLR4 protein and mRNA expression between groups LP and HP （ P 〉 0.05）. The microscopic examination showed that lung injury was attenuated in groups LP and HP as compared with group ALI. Conclusion PHCD pretreatment can protect lung against LPS-induced ALI through inhibiting CD14 and TLR4 activities.