卢帕他定干预兔油酸型急性肺损伤的研究  

Protective effect of rupatadine against oleic acid-induced acute lung injury in rabbits

作　　者：张林丽[1] 陆晶[1] 余书勤[1] 何建林[1] 周敏[1] 绪广林[1] 

机构地区：[1]南京师范大学生命科学学院新药中心江苏省医学分子生物学重点实验室,江苏南京210097

出　　处：《药学学报》2007年第3期252-256,共5页Acta Pharmaceutica Sinica

摘　　要：急性肺损伤(ALI)就是通常所定义的急性非心源性的水肿性肺损伤,是临床重症监护病人主要的死亡原因。本研究以油酸静注制备新西兰兔ALI模型,检测动脉血气参数变化,测定支气管肺泡灌洗液(BALF)中蛋白和血小板活化因子(PAF)、细胞间粘附分子-1(ICAM-1)及白细胞介素-8(IL-8)的含量,检测肺湿/干重(W/D)比值,观察组织病理学变化。结果表明,卢帕他定能抑制兔油酸型ALI的Pao2的下降,降低BALF中PAF,ICAM-1和IL-8的含量,减少蛋白渗出,降低肺W/D比值,减轻肺组织病理学损伤。卢帕他定可明显改善兔ALI,作用机制可能与抑制炎症因子合成与释放有关。Acute lung injury （ALI） makes up a spectrum of disease that is commonly defined as ＂acute non-cardiogenic edematous lung injury＂. It may contribute to morbidity and mortality in the critically ill patient in the intensive care unit. ALI was induced by oleic acid in rabbits. During the experiment, blood samples were taken from cervical artery and subjected to blood-gas analysis at different time points after oleic acid injection. Shortly after the rabbits were killed at 3 hour after iv OA injection, bronchoalveolar lavage fluid （BALF） was colleted, and the concentrations of protein, platelet-activating factor （PAF）, intercellular adhesion molecule-1 （ICAM-1）, interleukin 8 （IL-8） in BALF were then measured by ELISA. The ratio of wet to dry weight （W/D） of left lung was calculated to assess alveolar edema. Lung tissue was fixed in formaldehyde and stained with HE, and examined under a light microscope. The OA-induced elevation of arterial blood oxygen pressure was inhibited, as well as PAF, ICAM-1, IL-8 in BALF in rupatadine group. Furthermore, rupatadine also decreased the concentration of protein in BALF and inhibited the increase of the W/D weight ratio significantly. Light microscopic findings showed that the damage in rupatadine groups was far less severe than that in OA model group. Pretreatment with rupatadine has a beneficial effect on acute lung injury induced by oleic acid in rabbits. The ultimate reduction of inflammatory factors was involved, at leasi in part, in the mechanism of action of rupatadine effects.

关 键 词：卢帕他定 急性肺损伤 支气管肺泡灌洗液 血小板激活因子 

分 类 号：R965[医药卫生—药理学]