摘要目的 探讨盐酸戊乙奎醚对大鼠胸部撞击致急性肺损伤及肺组织Toll样受体4(TLR4)表达的影响.方法 健康雄性SD大鼠96只,体重250～300 g,采用随机数字表法,将大鼠随机分为3组(n=32):对照组(C组)只麻醉,不制备模型;肺损伤组(ALI组);盐酸戊乙奎醚组(PHcD组)模型制备后即刻,腹腔注射盐酸戊乙奎醚2 mg/kg.砝码(300g)于95 cm高处自由落体撞击大鼠心前区以制备急性肺损伤模型.于模型制备后2、8、12和24h时取8只大鼠,取动脉血样,测定血清TNF-α浓度.于模型制备后8 h取8只大鼠,取动脉血样,行动脉血气分析,随后处死大鼠,取肺组织观察病理学结果,测定干/湿重比(W/D比)、髓过氧化物酶(MPO)活性和TLR4表达水平.结果 与c组比较,ALI组和PHCD组pH值和PaO2下降,PaCO2、乳酸浓度、肺组织MPO活性、W/D比及TLR4表达和血清TNF-α浓度升高(P＜0.01);与ALI组比较,PHcD组pH值和PaO2升高,PaCO2、乳酸浓度、肺组织MPO活性、W/D比及TLR4表达和血清TNF-α浓度降低(P＜0.05).PHcD组肺组织病理性损伤较ALI组减轻.结论 盐酸戊乙奎醚可减轻大鼠胸部撞击诱发的急性肺损伤,其机制与下调肺组织TLR4表达,降低炎性反应有关.

abstractsObjective To investigate the effects of penehyclidine hydrochloride (PHCD) on acute lung injury (ALI) induced by blunt chest trauma and Toll-like receptor 4 (TLR4) expression in the lung tissues in rats.Methods Ninety-six male SD rats weighing 250-300 g were randomly divided into 3 groups ( n = 32 each):control group (group C), ALI group and PHCD group. ALI was induced by dropping a 300 g weight onto a precordial protective shield to direct the impact force away from the heart and toward the lungs in anesthetized rats according to the method described by Raghavendran et al. PHCD 2 mg/kg was injected intraperitoneally immediately after ALI was induced in group PHCD. Eight rats were selected at 2, 8, 12 and 24 h after ALI was induced, and arterial blood samples were collected for determination of the serum TNF-α concentration. Eight rats were selected at 8 h after ALI was induced, arterial blood samples collected for blood gas analysis and then the rats sacrificed. The lungs were immediately removed for determination of W/D lung weight ratio, myeloperoxidase (MPO) activity and TLR4 expression, and microscopic examination. Results The pH value and PaO2 were significantly lower, and the PaCO2, lactic acid level, MPO activity, W/D ratio, TLR4 expression and serum TNF-α concentration higher in groups ALI and PHCD than in group C (P ＜ 0.01 ). The pH value and PaO2 were significantly higher, and the PaCO2, lactic acid level, MPO activity, W/D ratio, TLR4 expression and serum TNF-α concentration lower in group PHCD than in group ALI ( P ＜ 0.05). The lung histopathologic damage was significantly ameliorated in PHCD group as compared with ALI group. Conclusion PHCD can protect the lungs against blunt chest trauma-induced ALI, and the down-regulation of TLR4 expression in lung tissues and reduction of inflammatory response are involved in the mechanism.