The ultra-early protective effect of ulinastatin on rabbit acute lung injury induced by paraquat.
The ultra-early protective effect of ulinastatin on rabbit acute lung injury induced by paraquat.
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DOI：
10.1186/1471-227x-13-s1-s7
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发表时间：
2013
影响因子：
2.5
通讯作者：
Ao G
中科院分区：
文献类型：
--
作者：
Song Z;Chen G;Lin G;Jia C;Cao J;Ao G
研究百草枯（PQ）致家兔急性肺损伤（ALI）超早期病理生理变化，探讨乌司他丁对PQ致ALI的超早期保护作用。将30只新西兰白色家兔随机分为对照组、百草枯组和乌司他丁干预组，每组10只。百草枯组和干预组单次腹腔注射百草枯（35 mg/kg）建立急性肺损伤模型。对照组注射等量生理盐水。干预组在建立ALI模型后立即给予乌司他丁100 Ku/kg。分别于造模后2 h、4 h、6 h时间点行320层螺旋CT胸膜灌注扫描，获取CTP（CT Perfusion）图像及相关参数。耳缘静脉采血2 mL，测定血管内皮生长因子（VEGF）质量浓度。6 h后空气栓塞处死动物，取肺组织进行病理学观察。百草枯组2、4、6 h的局部血流量（rBF）和局部血容量（rBV）均显著低于对照组（P <0.05）。干预组rBF和rBV在2、4、6 h时间点均显著高于百草枯组（P <0.05）。百草枯组在2、4、6 h时相点的通透性表面积（rPS）和VEGF质量浓度显著高于对照组（P <0. 05），干预组在2、4、6 h时相点的rPS和VEGF质量浓度显著低于百草枯组（P <0. 05）。百草枯组病理检测指标（充血毛细血管百分比、毛细血管外红细胞数、基底膜损伤毛细血管百分比）在6 h时间点均显著高于对照组（P <0. 05），干预组显著低于百草枯组（P <0. 05）。光镜下病理观察百草枯组可见明显炎性细胞浸润，肺泡上皮细胞增生，肺泡间隔增宽，可见局灶性出血，细支气管腔内可见急、慢性炎性细胞浸润;电镜下肺泡上皮细胞变性坏死，内皮细胞血管肿胀，基底膜破裂，肺泡腔内有大量渗出物。干预组上述症状均减轻。PQ致兔ALI超早期，肺血管内皮细胞受损，血清VEGF质量浓度升高，肺血管通透性增加。早期乌司他丁干预可降低血清VEGF水平和PQ诱导的血管通透性振幅，表明乌司他丁对肺血管内皮细胞具有保护作用。
To study ultra-early pathophysiological changes of rabbit acute lung injury (ALI) caused by paraquat (PQ) and discuss the ultra-early protective effect of ulinastatin on rabbit ALI due to PQ. 30 New Zealand white rabbits were randomly divided into a control group, a paraquat group and an ulinastatin intervention group with 10 rabbits in each group. For paraquat group and intervention group a single dose of paraquat (35mg/kg) was injected intraperitoneally to establish rabbit models of ALI. The control group was injected an equal volume of saline. The intervention group was treated with 100Ku/kg ulinastatin immediately after the establishment of the ALI model. The respective experimental groups underwent 320-slice CT perfusion scan of pleural at 2h, 4h and 6h time point after modeling to get CTP (CT Perfusion) images and related parameters. 2mL blood was collected in the marginal ear vein to determine the mass concentration of the vascular endothelial growth factor (VEGF). The animals were killed by air embolism after 6h and lung tissue was taken for pathology observation. The reginal blood flow (rBF) and reginal blood volume (rBV) of paraquat group at 2,4,6 h time point were significantly (P <0.05) lower than those of control group. The intervention group rBF and rBV at 2, 4 and 6 h time points were significantly higher (P <0.05) compared to paraquat group. The permeability surface (rPS) and VEGF mass concentration of paraquat group at 2,4,6 h time point were significantly higher than the control group (P <0.05), and the intervention group rPS and VEGF mass concentrations at 2,4,6h time point were significantly lower (P <0.05) than those of paraquat group. Pathological detection indicators of paraquat group (congestive capillary percentage, the number of red blood cells outside of capillaries, percentage of capillaries with basement membrane damage) were significantly higher (P <0.05) at 6h time point compared with the control group, while significantly lower (P <0.05) in intervention group than in paraquat groups. Pathological observation under light microscope showed in paraquat group obvious inflammatory cell infiltration, alveolar epithelial cell hyperplasia, widened alveolar septum, visible focal hemorrhage, visible acute and chronic inflammatory cell infiltration in bronchioles cavity; under electron microscopy alveolar epithelial cell degeneration and necrosis, vascular welling of the endothelial cells, basement membrane rupture, a lot of exudates in alveolar space. In the intervention group, the above the symptoms were mitigated. In the ultra-early stage of rabbit ALI induced by PQ, pulmonary vascular endothelial cell is damaged and serum VEGF mass concentration and pulmonary vascular permeability increase. Early ulinastatin intervention can reduce serum VEGF level and PQ-induced vascular permeability amplitude, indicating that ulinastatin has a protective effect on pulmonary vascular endothelial cells.