内毒素致兔早期急性肺损伤及氯喹的保护性作用

Endotoxin-induced early acute lung injury in rabbits and the protective effects of chloroquine

  • 摘要: 目的: 研究内毒素(ET)致兔早期急性肺损伤(ALI)的病理生理过程,探讨氯喹对ET所致的兔早期ALI的保护性作用。方法: 大耳白兔随机分为对照组、ET致伤组、ET致伤+氯喹干预组。静脉注射ET(500μg/kg)复制兔早期ALI的动物模型。测定动脉血气、血清及肺组织中磷脂酶A2(PLA2)活性、肺组织脂质过氧化物(LPO)含量和超氧化物歧化酶(SOD)的活性,并取肺组织行光镜及电镜下病理学观察。结果: 与对照组相比,静注ET后,致伤组动物出现动脉血氧分压(PaO2)下降、肺内白细胞扣押、血清及肺组织中PLA2活性增高、肺组织LPO含量增高(P<0.05)和SOD活性降低(P<0.05)。组织病理学观察可见致伤组肺组织出现了典型的ALI改变。干预组PaO2未见下降,血清及肺组织PLA2活性和肺组织LPO含量低于致伤组(P<0.05),肺组织SOD活性则高于致伤组(P<0.05),组织病理学观察显示肺损伤程度较轻。结论: 静脉注射ET可复制兔早期ALI的动物模型,PLA2激活及氧化损伤在ALI的病理生理过程中起重要作用;氯喹可抑制PLA2激活和氧化损伤,对ET所致的兔早期...

     

    Abstract: Objective: To study the pathophysiology process of endotoxin-induced early acute lung injury(ALI) in rabbits, and to research the protective effects of chloroquine on it. Methods: Rabbits were randomly assigned to three groups: control group, ET group, and ET+chloroquine group. ALI was induced by intravascular injection of ET (500μg/kg). The arterial partial pressure of oxygen (PaO2 ), phospholipase A2 (PLA2 )activities both in serum and lung tissue, lipid peroxide(LPO)contents and superoxide dismutase(SOD) activities in lung tissue were measured in our experiment. Electron microscope and light microscope were used to observe the pathological injuries in pulmonary tissue. Results: Compared with control group, rabbits treated with ET displayed PaO2 decrease, leukocyte sequestration in lung tissue, PLA2 activity increase both in serum and pulmonary tissues, the increase of pulmonary LPO contents (P<0.05) and the decrease of SOD activities (P<0.05). Typical pulmonary histopathological injuries were presented in ET group. In chloroquine group, PaO2 showed no decrease, PLA2 activities both in serum and pulmonary tissue and LPO contents were lower than ET group (P<0.05), and SOD activities were higher than those of ET group (P<0.05). The pulmonary histopathological injuries of chloroquine group showed slightly. Conclusion: Intravascular injection of ET can be used to induce early ALI in rabbits, and PLA2 activation and oxidative injury played important roles in the pathophysiology process of early ALI.Chloroquine can inhibit PLA2 activation and oxidative injury, which can alleviate the degree of ET-induced early ALI in rabbits to some extent.

     

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