小鼠急性脂肪栓塞综合征模型中炎症因子及炎症信号通路的激活

Activation of proinflammatory cytokines and transduction pathways in acute fat embolism syndrome mouse model

目的研究急性脂肪栓塞动物模型中炎症因子的激活及可能的信号转导途径。方法经健康雄性C57小鼠尾静脉注射同种异体小鼠肾周脂肪建立小鼠脂肪栓塞模型,采用Bliss法求出脂肪栓塞的半数致死剂量(LD50)。比较实验组(静脉注射LD50的脂肪)和对照组(给予相同剂量的生理盐水)大体和镜下肺组织表现、动脉血气、肺组织干湿质量比值(D/W)、肺组织髓过氧化物酶(MPO)活性、血浆IL-1β、TNF-α水平以及肺组织匀浆液中IKKβ基因和NF-κB蛋白的表达。结果与对照组相比,实验组肺组织呈严重损伤表现,血管腔和肺泡腔中有脂滴存积,肺组织D/W明显上升;实验组小鼠动脉血PaO2明显降低,PaCO2升高,血浆IL-1β和TNF-α水平显著上升,肺组织MPO活性升高,IKKβ基因表达上调,核转录因子NF-κB表达升高(P<0.05)。结论炎症反应在脂肪栓塞综合征病理过程中发挥了重要作用,NF-κB相关基因和蛋白表达升高提示NF-κB介导的炎症信号通路参与了脂肪栓塞激发的炎症病理过程。

Objective To investigate the function of proinflammatory cytokines in the animal model of fat embolism syndrome and its potential signal transduction pathways. Methods The fat embolism model was established by injection with the allogeneic perinephric fat through the caudal veins of healthy male C57BL mice. The half lethal dose （LD50） was calculated by Bliss′ method. Mice in experiment group were injected with LD50 of fat, and those in control group were managed with the same dose of normal saline. The lung tissue damage （both gross and microscope）, arterial blood gas, ratio of lung tissue wet and dry weight （D/W）, activity of myeloperoxidase （MPO） in lung tissues, plasma IL-1β and TNF-α levels and expression of IKK β gene and NF-κB protein in lung tissue homogenate were compared between groups. Results Compared with control group, the lung tissues were seriously damaged, there was lipid droplet accumulation in the endovascular and alveolar space, and D/W increased in experiment group. In experiment group, the arterial oxygen partial pressure （PaO2） significantly decreased, the arterial carbon dioxide partial pressure （PaCO2） increased, plasma IL-1β and TNF-α significantly increased, the activity of MPO in lung tissues enhanced, and the expression of IKKβ gene and NF-κB increased （P〈0.05）. Conclusion Inflammatory reaction plays an important role in the pathological process of fat embolism syndrome, and the increase of NF-κB related gene and protein indicates the participation of the inflammatory signal pathways mediated by NF-κB.