内毒素致兔急性肺损伤及磷脂酶A_2致伤机制的研究

The role of phospholipase A_2 in endotoxin-induced acute lung injury in rabbits

目的 :研究大肠杆菌内毒素致兔急性肺损伤 (ALI)发病机制及磷脂酶A2 (PLA2 )激活在此病理生理过程中的致伤机制。方法 :大耳白兔随机分为对照组、内毒素致伤组、内毒素致伤 +氯喹干预组。静脉注射内毒素(5 0 0 μg/kg)引起兔ALI,测定血清及肺组织中PLA2 活性、动脉血气分析及肺组织病理改变。观察PLA2 抑制剂氯喹对ALI病理生理过程的影响。结果 :静注内毒素后兔出现氧分压下降 (P <0 .0 5 )、肺水肿、肺内炎细胞浸润、透明膜形成、上皮细胞及内皮细胞受损等早期ALI病理生理改变。损伤组兔血清及肺组织中PLA2 活力高于静注内毒素前及正常对照组 (P <0 .0 1)。氯喹干预组氧分压未见下降 ,血清及肺组织中PLA2 活力较对照组增高 (P <0 .0 1)但低于内毒素组 (P <0 .0 5 )。结论 :静脉注射内毒素可诱导兔早期ALI ,PLA2 激活在此病理生理过程中起了重要作用。应用PLA2 抑制剂氯喹可抑制内毒素致伤后PLA2 激活 ,从而缓解内毒素引起的低氧血症 。

objective: To study the pathogenesis of acute lung injury (ALI) of rabbits induced by intravascular injection of endotoxin (ET), as well as the role of the activation of phospholipase A 2(PLA 2). Methods: Rabbits were randomly assigned to three groups: control group, ET group, and chloroquine group(treated by both ET and chloroquine). Acute lung injury was induced by intravascular injection of ET (500 μg/kg). The PLA 2 activity in serum and pulmonary tissue and the arterial gas analyses were measured before and after ET injection in three groups. Electron microscope and light microscope were used to observe the pathological damages in the pulmonary tissue. The protective effects of chloroquine were both observed and analyzed. Results:Compared with saline controls, rabbits treated with ET showed the early damage of ALI, such as the decrease of PaO 2, pulmonary edema, endothelial and epithelial cells injury. The PLA 2 activity significantly increased in ET group compared with the basal activity and control group (P<0.01). In chloroquine group, the PLA 2 activity was higher than control group (P<0.01), but lower than ET group (P<0.05). Conclusion:Intravascular injection of ET induced ALI in rabbits. PLA 2 activation played an important role in the pathogenesis of ALI. The inhibitor of PLA 2, chloroquine, reduced the hypoxia and PLA 2 activation caused by ET, therefore could alleviate the early damages in lung tissue induced by ET injection.