氟比洛芬酯预先给药对大鼠内毒素性急性肺损伤的影响

目的 评价氟比洛芬酯预先给药对大鼠内毒索性急性肺损伤的影响.方法 雄性SD大鼠40只,体重190～220 g,随机分为3组:对照组(C组,n=8)、脂多糖组(LPS组,n=16)和氟比洛芬酯组(FA组,n=16).C组尾静脉注射生理盐水(NS)1 ml;LPS组尾静脉注射LPS 5 mg/kg(1 m1);FA组尾静脉注射氟比洛芬酯6 mg/kg(1 m1)后0.5 h注射LPS 5 mg/kg(1 m1).LPS组和FA组于注射LPS后2、4 h时、C组于注射NS后4 h时,各随机处死8只大鼠,取股动脉血样8 ml,行血气分析;采用放免法测定血清血栓素B2(TXB2)和6-酮-前列腺素F1α(6-keto PGF1α)的浓度;采用ELISA方法测定血清肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、IL-6和IL-10的浓度.取左肺上叶组织,计算肺组织湿/干重比值(W/D)和肺含水量(LC).注射LPS或NS后4 h时取左肺下叶组织,光镜下观察肺组织病理学结果.结果 与C组比较,LPS组PaO2和PaO2/FiO2下降,PaCO2、W/D和LC升高,血清TXB2、6-keto PGF1α浓度和TXB2/6-keto PGF1α比值升高,血清TNF-α、IL-1β和IL-6浓度升高,FA组W/D和LC升高,血清TXB2和6-keto PGF1α浓度升高,血清TNF-α、IL-1β、IL-6和IL-10浓度升高(P<0.05或0.01).与LPS组比较,FA组PaCO2、W/D和LC降低,PaO2和PaO2/FiO2升高,血清TXB2、6-keto PGF1α浓度和TXB2/6-keto PGF1α比值降低,血清IL-1β、IL-6和TNF-α浓度降低,血清IL-10浓度升高(P<0.05).FA组肺组织病理学损伤较LPS组轻.结论 氟比洛芬酯预先给药可减轻内毒素性急性肺损伤,可能与维持血液TXA2和PGI2平衡及抑制炎性反应有关.

Effect of flurbiprofen axetil pretreatment on LPS-induced acute lung injury in rats

Objective To investigate the effect of flurbiprofen axetil(FA)on the acute lung injury(ALI)induced by LPS in rats.Methods Forty male SD rats weighing 190-220 g were nmdomly divided into 3 groups:group Ⅰ control(C,n=8);groupⅡ LPS(n=16)and group Ⅲ FA+LPS(n=16).In group Ⅱ and Ⅲ LPS 5 mg/kg in 1 ml of normal saline(NS)w88 given iv.In group Ⅲ FA 6 mg/kg in NS 1 ml was given Ⅳ 0.5 hbefore LPS administration.In group Ⅱ and Ⅲ 8 animals were killed at 2 h(T1)and 4 h(T2)after LPS administration respectively.Blood samples were obtained at T1 and T2 for blood gas analysis and determination of serum TXB2,6-keto PGF1α(by radio-immuno assay),TNF-α,IL-1β,IL-6 and IL-10 concentrations(by ELISA).Lungs were removed for determination of W/D lung weight ratio,lung water content(LC)and microscopic examination.ResultsCompared with group C,LPS signitlcanfly decreased PaO2,PaO2/FiO2 and increased PaCO2,W/D lung weight ratio,LC,serum TXB2,6-keto-PGF1α concentrations,TXB2/6-keto-PGF1α ratio and serum IL-1β,TNF-α,and IL-6 concentrations in LPS group.Pulmonary edema and hemorrhage were observed in LPS group.FA pretreatment significantly attenuated LPS-induced blood gas,bio-chemical and pulmonary histological changes in group Ⅲ.Conclusion Flurbiprofen axetil pretreatment can protect the lungs against LPS-induced acute injury by down-regulating TXB2/6-keto-PGF1α ratio and inhibiting inflammatory response.