盐酸戊乙奎醚预先给药对失血性休克大鼠急性肺损伤时TLR4 mRNA表达的影响

Effect of penehyclidine pretreatment on Toll-like receptor 4 mRNA expression in the lung following acute lung injury induced by hemorrhagic shock in rats

目的 探讨盐酸戊乙奎醚预先给药对失血性休克大鼠急性肺损伤时Toll样受体4（TLR4）mRNA表达的影响.方法 健康SD大鼠40只,体重200～250 g,随机分为5组（n=8）：假手术组（S组）、失血性休克致急性肺损伤组（ALI组）和低、中、高剂量盐酸戊乙奎醚预先给药组（P1～3组）.S组仅行动静脉穿刺,不放血,ALI组股动脉放血至35～45 mm Hg制备急性肺损伤模型,P1～3组分别于放血前30 min股静脉注射盐酸戊乙奎醚0.3、1.0、3.0 mg/kg,随后制备急性肺损伤模型.各组复苏后4 h时处死大鼠取肺,称重后计算肺湿干重比,检测TLR4 mRNA和NF-κB p65蛋白的表达水平,观察病理学结果.结果 与S组比较,ALI组和P1组TLR4 mRNA、NF-κB p65蛋白表达水平及肺湿干重比升高（P＜0.05或0.01）,P2.3组差异无统计学意义（P＞0.05）;与ALI组比较,P2,3组TLR4 mRNA、NF-κB p65蛋白表达水平及肺湿干重比降低（P＜0.05或0.01）;P2组和P3组上述指标比较差异无统计学意义（P＞0.05）.P2,3组肺组织病理学损伤程度较ALI组明显减轻.结论 盐酸戊乙奎醚预先给药可通过抑制肺组织TLR4 mRNA表达上调,进而降低NF-κB活性,从而减轻失血性休克诱发大鼠的急性肺损伤.

Objective To investigate the effect of penehyclidine （PHCD） pretreatment on Toll-like receptor 4 （TLR4） mRNA expression in the lung following acute lung injury （ALI） induced by hemorrhagic shock in rats. Methods Forty healthy SD rats of both sexes weighing 200-250 g were randomly divided into 5 groups（ n = 8 each）： group Ⅰ sham operation （group S）; group Ⅱ ALI （group ALI）; group Ⅲ, Ⅴ, PHCD 0.3,1.0, 3.0 mg/kg were given iv respectively at 30 min before hemorrhagic shock （P1-3）. Hemorrhagic shock was induced by exsanguinations. MAP was maintained at 35-45 mm Hg for 60 min. The animals were killed at 4 h after resuscitation. Their lungs were removed for microscopic examination, W/D lung weight ratio and determination of TLR4 mRNA expression in the lung tissue （by RT-PCR）. NF-κB p65 protein expression in the lung tissue was determined （by immuno-histochemical staining）. Results Hemorrhagic shock significantly increased TLR4 mRNA and NF-κB p65 protein expression in the lung tissue and W/D lung weight ratio. Pretreatment with PHCD 1.0 or 3.0 mg/kg significantly inhibited hemorrhagic shock-induced increase in TLR4 mRNA and NF-κB p65 protein expression in the lung and W/D lung weight ratio. The lung injury was significantly ameliorated in group P2,3 as compared to group ALI. Conclusion PHCD pretreatment can attenuate ALI induced by hemorrhagic shock through down-regulation of TLR4 mRNA expression and decreasing NF-κB activity in the lung.