论文部分内容阅读
目的采用氯喹干预的方法,研究大肠杆菌内毒素(ET)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。
Objective To investigate the mechanism of early acute lung injury induced by endotoxin (ET) in rabbits by chloroquine intervention. Methods Large white rabbits were randomly divided into control group, ET injury group, ET injury + chloroquine treatment group. Intravenous injection of ET (500μg / kg) induced early lung injury in rabbits. Arterial blood gas analysis, peripheral leukocytes and platelet counts, phospholipase A2 (PLA2) activity in serum and lung tissue, LPO, , The changes of superoxide dismutase (SOD), lung tissue was taken for pathological examination by light and electron microscopy to observe the injury of ET and the effect of PLA2 inhibitor chloroquine on the pathophysiology of early lung injury. Results In rabbits, the pathological changes of early lung injury such as the decrease of arterial partial pressure of oxygen (PaO2), the decrease of peripheral white blood cells and thrombocytopenia, the sequestration of leukocytes in the lung, etc. PLA2 activity in serum and lung tissue of ET group increased, LPO increased in lung tissue (P <0.05), and SOD decreased significantly (P <0.05). Pathological examination of ET group showed pulmonary edema, part of lung tissue flake hemorrhage, inflammatory cell infiltration, transparent membrane formation, with focal atelectasis and emphysema. The ultrastructural changes showed type Ⅰ and type Ⅱ alveolar epithelial cell injury, swollen vascular endothelial cells and obvious thickening of alveolar septum. There was no decrease of PaO2 in serum of chloroquine group and PLA2 activity in serum and lung tissue (P <0.01) ), Pathological examination showed mild pulmonary edema, inflammatory cell infiltration less than ET group, lung tissue ultrastructural examination showed less damage than ET group. Conclusion Intravenous injection of ET can replicate the model of early lung injury in rabbits. Chloroquine can inhibit the activation of PLA2 and reduce the oxidative damage in lung tissue. The results confirmed that PLA2 activation and oxidative stress have the potential of causing ET-induced acute lung injury in rabbits Important role.