环孢菌素A对脂多糖诱导的小鼠急性肺损伤的保护作用

目的：探讨线粒体渗透性转换孔道抑制剂环孢菌素A（CsA）对脂多糖（LPS）诱导的小鼠急性肺损伤可能的保护作用。方法：LPS 4 mg/kg气管内滴入复制小鼠急性肺损伤模型,实验随机分为5组（n=24）：分别为正常对照组、LPS组、地塞米松组、CsA组和CsA＋苍术苷组。6 h后小鼠处死,测定各组支气管肺泡灌洗液乳酸脱氢酶（LDH）的含量,酶联免疫吸附法测定肺组织匀浆液TNF-α浓度,测定肺组织湿/干重比和肺毛细血管通透性指数。结果：气管内滴入LPS 6 h后,CsA组与LPS组相比,肺泡灌洗液中LDH活性降低,肺组织匀浆液TNF-α浓度下降,肺组织湿/干重比、肺毛细血管通透性指数均明显下降,但CsA＋Atr组与LPS组相比无明显区别。结论：环孢菌素A对脂多糖诱导的小鼠急性肺损伤有保护作用,其机制可能与其抑制线粒体渗透性转换孔道的开放有关。

The effect of cyclosporine A on lipopolysaccharide-induced acute lung injury in mice

Objective： To investigate the effect of mitochondrial permeability transition pore inhibitor cyclosporine A（CsA） on lipopolysaccharide（LPS）-induced acute lung injury in mice.Methods： All male ICR mice were randomly divided into five groups（n=24）： control group,LPS group,dexamethasone group,cyclosporine A（CsA） group and CsA ＋ atractyloside（Atr） group.Six hours after treatment with LPS,the activity of lactate dehydrogenlase（LDH） in bronchoalveolar lavage fluid（BALF） and level of tumor necrosis factor-α（TNF-α） in lung tissue were detected.The lung wet weight/dry weight ratio and the pulmonary capillary permeability index were also detected.Results： In contrast to LPS group,the mitochondrial permeability transition pore inhibitor CsA induced a decrease in LDH activity in the BALF and TNF-α level in lung tissue,lung wet weight/dry weight ratio and the pulmonary capillary permeability index were declined.Atractyloside,the activator of mitochondrial permeability transition pore,almost abolished the role of CsA on LPS-induced lung injury.Conclusion： These results suggested that CsA plays the protective effect on LPS-induced lung injury in mice,it is likely through inhibiting the opening of mitochondrial permeability transition pore.