Wy14643对大鼠呼吸机相关性肺损伤的影响

Effect of peroxisome proliferator-activated receptor α agonist on mechanical ventilation＇induced lung injury in rats

目的 探讨过氧化物酶体增殖物激活受体a激活剂——wy14643对大鼠呼吸机相关性肺损伤的影响。方法健康雄性SD大鼠32只，随机分为4组（n=8）：对照组（c组）、机械通气组（V组）、不同剂量Wy14643组（w1组和W1组）。C组不行机械通气，其余3组均行大潮气量（VT，T40ml／kg）机械通气2h。W1组和取组分别于机械通气前1h经颈外静脉注射wy14643（溶于10％二甲亚砜）1、3mg／kg，C组和V组于机械通气前1h经颈外静脉注射10％二甲亚砜1ml／kg。于机械通气前、机械通气1、2h时取股动脉血样行血气分析，计算Pa0：／Fiq（氧合指数）。通气2h后收集支气管肺泡灌洗液（BALF）测定TNF-α和巨噬细胞炎症蛋白-2（MIP-2）的水平，取肺组织计算湿重／干重比（W／D比），取动脉血样，测定血清MDA、SOD水平，光镜下观察肺组织病理学。结果与c组比较，v组SOD水平降低，TNF-α、MIP-2、MDA的水平和W／D比升高（P〈0．05），肺组织病理学损伤明显；与v组比较，w1组和w2组氧合指数和SOD水平升高，TNF-α、MIP-2、MDA的水平和W／D比降低（P〈0．05），肺组织病理学损伤程度减轻。与w，组比较，M组氧合指数和SOD水平升高，TNF-α、MIP-2、MDA的水平和W／D比降低（P〈0．05）。结论wy14643可减轻大鼠呼吸机相关性肺损伤，且与剂量有关。

Objective To investigate the effect of peroxisome proliferator-activated receptor a agonist - Wy14643 on mechanical ventilation-induced lung injury in rats. Methods Thirty-two healthy male SD weighing 250-300 g were randomly divided into 4 groups （ n = 8 each） ： group Ⅰ control （group C） ; group Ⅱ mechanical ventilation （group V） and group Ⅲ , Ⅳ pretreated with different doses of Wy14643 （group W1, W2 ）. The animals were anesthetized with intraperitoneal 3% pentobarbital 30 mg/kg and tracheostomized. The femoral artery and external jugular vein were cannulated for blood sampling and drug administration. Group C received no mechanical ventilation. In group V, W1 and W2 the animals were mechanically ventilated for 2 h （VT 40 ml/kg, RR 40 bpm,I： E = 1：2, FiO2 21% ）. In group W1 and W2 Wy14643 1 and 3 mg/kg were administered iv at 1 h before mechanical ventilation. Arterial blood samples were collected at 1 and 2 h of mechanical ventilation for determination of PaO2/FiO2 . Serum SOD activity and MDA concentration were measured at the end of 2 h mechanical ventilation. The animals were then killed and the lungs removed for microscopic examination, lung lavage and W/D lung weight ratio. The MIP-2 and TNF-α concentrations in BALF were measured. Results Two hour mechanical ventilation significantly decreased serum SOD activity and increased serum MDA concentration, W/D lung weight ratio and TNF-α and MIP-2 concentrations in BALF as compared with group C. Wy14643 pretreatment significantly attenuated these mechanical ventilation-induced changes in group W1 and W2 in a dose-dependent manner. Conclusion Wy14643 can attenuate mechanical ventilation induced lung injury in rats and it is related to the dose.