异丙酚对油酸性急性肺损伤大鼠肺表面活性蛋白A的影响

Effect of propofol on SP-A in oleic acid-induced acute lung injury of rats

目的观察油酸性急性肺损伤（Au）大鼠肺组织肺表面活性蛋白A（SP-A）的蛋白表达情况及异丙酚对该指标的影响，探讨异丙酚肺保护作用及其机制。方法80只雄性SD大鼠，体重250-290g，随机分成5组，每组16只：正常对照组（I组），Au组（Ⅱ组），异丙酚低剂量组（Ⅲ组）：4mg·kg^-1·h^-1，异丙酚中剂量组（Ⅳ组）：8mg·kg^-1·h^-1，异丙酚高剂量组（V组）：16mg·kg^-1·h^-1。静脉注射油酸250μl·kg^-1制备大鼠Au模型，Ⅲ-Ⅴ组持续静脉输注异丙酚4h之后处死大鼠。取每组8只大鼠肺组织，生化方法测定Na^＋-K^＋-ATP酶活性，RT-PCR测定肺组织SP-AmRNA蛋白表达；其余8只进行全肺支气管肺泡灌洗，留取支气管肺泡灌洗液（BALF），进行白细胞计数。结果与I组比较，Ⅱ组肺组织Na^＋-K^＋-ATP甲酶活性以及SP-AmRNA蛋白表达均显著减弱；B脚中白细胞数量及中性粒细胞比例均显著增加，淋巴细胞比例显著减少。给予不同剂量异丙酚治疗后（4、8、16mg·kg^-1·h^-1），与Ⅱ组比较，Ⅲ、Ⅳ、Ⅴ组肺组织Na^＋-K^＋-ATP酶活性均显著增强（P〈0．05），IV组肺组织SP-AmRNA蛋白表达显著增强（P〈0．05），V组肺组织SP-AmRNA蛋白表达显著减弱（P〈0．05），Ⅲ组肺组织SP-AmRNA蛋白表达无显著变化；Ⅲ、Ⅳ、Ⅴ组BALF中白细胞数量及中性粒细胞比例均显著减少（P〈0．05），淋巴细胞比例显著增加（P〈0．05）。结论异丙酚可以通过抑制油酸性Au时肺组织的炎性反应，降低肺水肿程度，减轻肺泡Ⅱ型上皮细胞损伤，降低肺组织SP-A降解，促进肺泡SP-A合成与分泌，维持肺泡Ⅱ型上皮细胞正常的结构与功能，从而发挥对油酸性AU的保护作用。

Objective To observe the effects of propofol on the expression of SP-A mRNA in Lung tissue of oleic acid-induced ALI rats.Methods Eighty male SD rats weighted 250 - 290g were anesthetized with intraperitoneal （i.p.） 20% urethane 6 ml· kg^-1. Left common carotid artery and right internal jugular vein were cannulated for monitoring blood pressure and administration of reagents. The animals were randomly divided into 5 groups （ n = 16, in each group）： group Ⅰ ：control group; group Ⅱ ： ALI group, oleic acid 250 μl· kg^-1 i.v. ; group Ⅲ： ALI＋ propofol 4 mg·kg^-1 ·h^-1; groupiv ：ALI＋ Propofol 8 mg·kg^-1 ·h^-1and groupV ：ALI＋ propofol 16 mg·kg^-1 ·h^-1 .After administration of oleic acid, the propofol at 4, 8 and 16 mg·kg^-1 ·h^-1 was continuously injected for 4 h, then the animals were killed. Lung of eight animals in each group was immediately resected for determination of SP-A mRNA ex- pressionby Reverse transcriptase-polymerase chain reaction analysis （RT-PCR） and Na^＋ -K^＋ -ATP ase activity was examined by biochemical assay. Lungs of other animals in each group were washed with icing saline. Then the BALF was sampled for counting WBC and its percentage of neutrophils. Results The expression of SP-AmRNA and the activity of Na^＋ -K^＋ -ATPase in Lung tissue was significantly decreased respectively, and WBC number and neutrophils percentage in BALF were significantly increased in group Ⅱ , compared with those of group Ⅰ . After admimstration of propofol, the activity of Na^＋ -K^＋ -ATP ase in lung tissne significantly increased and the WBC number and neutrophils percentage in BALF were markedly decreased compared with those of group Ⅱ . The expression of SP-A mRNA in lung tissue in group Ⅳ was significantly increased while the expression in group Ⅴ was significantly decreased, and there had no markedly changed in group m ,compared with those of group Ⅱ Conclusion, Propofol has a beneficial protective function on ALI induced by oleic acid through up-regulating SP-AmRNA in Lung tissue .