内毒素致兔早期急性肺损伤机制的探讨

目的采用氯喹干预的方法，研究大肠杆菌内毒素（日）致兔早期急性肺损伤的机制。方法大耳白兔随机分为对照组、ET致伤组、ET致伤＋氯喹治疗组。静脉注射ET（500μg／kg）引起兔早期肺损伤，测定动脉血气分析、外周血白细胞及血小板计数变化、血清及肺组织中磷脂酶A2（PLA2）活性、肺组织脂质过氧化物（LPO）、超氧化物歧化酶（SOD）变化，取肺组织进行光镜及电镜病理检查，观察ET的致伤作用及PLA2抑制剂氯喹对早期肺损伤病理生理过程的影响。结果静注ET后兔出现动脉血氧分压（PaO2）下降、外周血白细胞及血小板减少、肺内白细胞扣押等早期肺损伤病理改变。ET组血清及肺组织中PLA2活性增高，肺组织LPO增高（P〈0．05），SOD明显降低（P〈0．05）。ET组病理检查见肺水肿，部分肺组织片状出血，炎细胞浸润，透明膜形成，伴局灶性肺不张和肺气肿。超微病理改变表现为Ⅰ型、Ⅱ型肺泡上皮细胞损伤，血管内皮细胞肿胀，肺泡隔明显增厚。氯喹治疗组PaO2未见下降，血清及肺组织PLA2活性低于ET组（P〈0．05，P〈0．05），LPO降低（P〈0．01），SOD增高（P〈0．01），病理检查见轻度肺水肿，炎细胞浸润较ET组少，肺组织超微病理检查显示损伤轻于ET组。结论静脉注射ET可复制兔早期肺损伤动物模型，氯喹具有抑制PLA2激活、减轻肺组织内氧化损伤的作用，实验结果证实PLA2激活及氧化应激在ET致兔早期急性肺损伤的发病机制中具有重要作用。

Studies on pathogenesis of endotoxin-induced early acute lung injury in rabbits

Objective To study the role the pathogenesis of early acute lung injury (ALI) of rabbits induced by intravascular injection of endotoxin (ET) with the intervening method of Chloroquine. Methods Rabbits were randomly assigned to three groups: control group, ET group, and ET+ chloroquine group. Acute lung injury was induced by intravascular injection of ET (500μg/kg). The arterial gas analyses, leucocyte and platelet counts in peripheral blood, PLA2 activity both in serum and lung tissue, lipid peroxide (LPO) and superoxide dismutase (SOD) in lung tissue were measured. Electron microscope and light microscope were used to observe the pathological injuries in pulmonary tissue. The protective effects of chloroquine in early ALI were evaluated. Results Compared with saline controls, rabbits treated with ET displayed the early lung injuries, such as the decrease of PaO2 (P＜0.05), the decrease of leucocytes and platelets in peripheral blood, the leukocytes sequestration in lung tissue. The PLA2 activity significantly increased in ET group compared with control group and chloroquine group both in serum and pulmonary tissue. In ET group, concentration of LPO increased in lung tissue (P＜0.05), while concentration of SOD decreased (P＜0.05). Severe histopathological injuries were presented in ET group, including pulmonary edema, lung tissue haemorrhage, inflammatory cells infiltration, asphyxial membrand formation, partial pulmonary closure and emphysema.Ultrastructural changes showed both type Ⅰ and type Ⅱ epithelial cells injury in ET group, the edema of endothelial cells, interalveolar septum thickening. In chloroquine group, PaO2 didn't decrease, PLA2 activities in serum and pulmonary tissue were lower than ET group (P＜0.05, P＜0.05), while the concentration of LPO in lung tissue decreased (P＜0.01) and SOD increased significantly (P＜0.01). Pathological examination showed slight pulmonary edema, inflammatory cells infiltration were extenuated, ultrastructural examination proved that the injuries were alleviated by chloroquine compared with ET group. Conclusion Intravascular injection of ET could successfully induce the early ALI models in rabbits. Chloroquine could inhibit the PLA2 activation and reduce the oxidative injury in lung tissue. The experiment result demonstrated PLA2 activation and oxidative stress played important roles in the pathophysiological process of early ET-induced ALI in rabbits.