阿奇霉素对油酸致大鼠急性肺损伤的干预作用

Protective effect of azithromycin on acute lung injury induced by oleic acid in rat

目的应用油酸（oleic acid，OA）静脉注射复制大鼠急性肺损伤（acute lung injury，ALI）模型，探讨γ-干扰素（IFN-γ）、自介素4（IL-4）在OA性肺损伤中的变化规律；探讨阿奇霉素（AZI）对OA致ALI大鼠的治疗作用及其可能的作用机制。方法90只SD大鼠随机分为3组（每组30只）：生理盐水对照组（NC组）、OA致ALI组（OA组）、AZI治疗组（AZI组）。分别观察1d、3d和7d（每个时间点均10只），测定动脉血氧分压（PaO2）、动脉血二氧化碳分压（PaCO2）、pH值及血浆IL-4含量，左下肺测湿／干重比（wet／dry weight，W／D值），上段行病理检查。右肺灌洗，测支气管肺泡灌洗液（bronchoalveolar lavage fluid，BALF）中总蛋白（total proteins，TP）、IFN-γ、IL-4含量。结果与NC组比较，OA组各时间点W／D值、BALF中的TP均显著升高（P〈0．01），IFN-γ／IL-4、PaO2降低（P〈0．01），肺组织可见充血、水肿、出血，炎性细胞浸润等ALI表现；AZI组与OA组相比，肺组织病变减轻，IFN-γ／IL-4、PaO2升高（P〈0．05），W／D降低（P〈0．05）；OA组和AZI组各时间点血浆中IL-4浓度与BALF中IL-4浓度呈正相关（P〈0．01）。结论①ALI病程中存在Th1／Th2细胞因子失衡，IFN-γ分泌减少，IL-4分泌增加；②ALI时，测定血浆中IL-4浓度可以间接反映BALF中IL-4水平；③AZI可以部分纠正OA致大鼠ALI中Th1／Th2细胞因子失衡，对ALI有一定的治疗作用。

Objective To reproduce the model of acute lung injury（ALI） in rats by injecting oleic acid （OA） into the vein,and investigate the alterations of interferon gamma（IFN-γ）, interleukin-4 （IL-4） after ALI induced by OA,and explore the possible mechanisms of protective effects of azithromyein（AZI） in OA induced ALI in rats. Methods Ninety adult Sprague-Dawley rats were randomly divided into three groups： normal control group treated by saline injection （NC group）, ALI group induced by OA injection （OA group） ,therapy group treated by oral azithromycin （ AZI group）. Arterial oxygen tension（PaO2 ）, arterial carbon dioxide tension（PaCO2 ）, pH value and plasma interleukin-4 level were assayed after the animals were exsanguinated and sacrificed at 1,3 and 7 days later. The left lower lung was used to calculate wet/dry mass ratio（W/D） ,histopathology,whereas the right lung was lavaged and the total proteins（TP）,IFN-γ and IL-4 concentration in the bronchoalveolar lavage fluid（BALF） were determined. Results In OA group,W/D,TP in the BALF were significantly increased （P〈 0.01）, whereas the ratio of IFN-γ/IL-4, PaO2 were significantly decreased（ P 〈0.01） as compared with those of NC group. Obvious pathological manifestations such as hyperemia, edema, hemorrhage, neutrophil infiltration were shown. In AZI group, the change of lung pathology was significantly relieved, the ratio of IFN-γ/IL-4, PaO2 were increased （ P 〈 0.05）, W/D was significantly decreased （ P 〈0.05） as compared with that of OA group. IL-4 concentrations in the BALF were positively correlated to those in the plasma in OA and AZI group at the same time point （ P 〈0.01）. Conclusions （1）The imbalance of Th1/Th2 type eytokines is confirmed in ALI, with the concentration of IFN-γ decreasing and the concentration of IL-4 increasing; （2）IL-4 concentration in plasma may reflect indirectly IL-4 concentration in BALF of ALI rats;（3）AZI may incompletely shift the Thl/Th2 imbalance, lessening the development of ALI to some extent.