基于VEGFA/SDF-1/CXCR4通路探讨乌司他丁对脑卒中相关性肺炎大鼠肺组织的保护作用  

Exploring the protective effect of ulinastatin on the lung tissue in rats with stroke-related pneumonia based on VEGFA/SDF-1/CXCR4 pathway

作　　者：王淑霞[1] 王秀霞[1] 宋彦峰[1] WANG Shuxia;WANG Xiuxia;SONG Yanfeng(Department of Neurology,the Second People's Hospital of Liaocheng,Liaocheng 252600,China)

机构地区：[1]聊城市第二人民医院神经内科,山东聊城252600

出　　处：《现代医学》2022年第8期946-952,共7页Modern Medical Journal

摘　　要：目的:基于血管内皮生长因子A(VEGFA)/基质细胞衍生因子-1(SDF-1)/CXC型趋化因子受体(CXCR4)通路探讨乌司他丁对脑卒中相关性肺炎大鼠肺组织的保护作用。方法:2021年1月至2021年6月,构建脑卒中相关性肺炎(SAP)大鼠模型共48只,将其随机平分为4组:模型组、乌司他丁(100 kU·kg^(-1))组、AMD3100(CXCR4抑制剂,剂量:2.5 mg·kg^(-1))组、乌司他丁(100 kU·kg^(-1))+AMD3100(2.5 mg·kg^(-1))组,再选取12只SD大鼠设定为假手术组。以药物分组干预后,测定大鼠动脉血氧分压(PaO_(2))和二氧化碳分压(PaCO_(2))、肺泡灌洗液(BALF)中白细胞计数、肺组织湿干重比值、血清炎性介质活性氧(ROS)、白细胞介素(interleukin,IL)-18、IL-6水平及肺组织VEGFA/SDF-1/CXCR4通路蛋白表达,观察大鼠肺组织病理损伤改变并做Holfbauer评分。结果:与假手术组比较,模型组大鼠动脉血PaCO_(2)[(59.03±4.95)vs.(33.97±2.38)mmHg]、白细胞计数[(80.96±16.15)vs.(22.74±4.26)×10^(6)/ml]、湿干重比值[(6.20±0.43)vs.(4.41±0.32)]、Holfbauer评分[(2.53±0.42)vs.(0.00±0.00)分]、血清ROS[(232.05±31.72)vs.(112.47±16.84)mmol·L^(-1)]、IL-18[(3.71±0.38)vs.(0.64±0.12)ng·ml^(-1)]和IL-6[(1.23±0.14)vs.(0.11±0.03)ng·ml^(-1)]水平显著升高,动脉血PaO_(2)[(65.75±5.09)vs.(98.12±8.25)mmHg]、肺组织VEGFA[(0.49±0.07)vs.(1.31±0.22)]、SDF-1[(0.41±0.09)vs.(1.28±0.15)]、CXCR4[(0.55±0.12)vs.(1.43±0.26)]蛋白表达水平显著降低,差异均有统计学意义(P<0.05)。与模型组、乌司他丁+AMD3100组分别比较,乌司他丁组大鼠动脉血PaCO_(2)、白细胞计数、湿干重比值、Holfbauer评分、血清ROS、IL-18和IL-6水平均显著降低,动脉血PaO_(2)、肺组织VEGFA、SDF-1、CXCR4蛋白表达水平均显著升高,差异均有统计学意义(P<0.05),而AMD3100组大鼠动脉血PaCO_(2)、白细胞计数、湿干重比值、Holfbauer评分、血清ROS、IL-18和IL-6水平均显著升高,PaO_(2)、肺组织VEGFA、SDF-1、CXCR4蛋白表达水平Objective:To explore the protective effect of ulinastatin on the lung tissue of rats with stroke-associated pneumonia based on the vascular endothelial growth factor A(VEGFA)/stromal cell-derived factor-1(SDF-1)/CXC chemokine receptor(CXCR4)pathway.Methods:From January 2021 to June 2021,a total of 48 rats were used to establish a stroke-associated pneumonia(SAP)model and randomly grouped into four groups:model group,ulinastatin((100 kU·kg^(-1))group,AMD3100(CXCR4 inhibitor,dose:2.5 mg·kg^(-1))group,and ulinastatin(100 kU·kg^(-1))+AMD3100(2.5 mg·kg^(-1))group,and another 12 SD rats were allocated into sham operation group.After grouping and intervention with drugs,the arterial blood oxygen partial pressure(PaO_(2))and carbon dioxide partial pressure(PaCO_(2)),white blood cell count in alveolar lavage fluid(BALF),lung tissue wet-to-dry weight ratio,the levels of serum inflammatory mediator reactive oxygen species(ROS),interleukin(IL)-18 and IL-6,and the expressions of lung tissue VEGFA/SDF-1/CXCR4 pathway proteins were measured,the pathological changes of rat lung tissue were observed,and Holfbauer score was made.Results:Compared with the sham operation group,the arterial blood PaCO_(2)[(59.03±4.95)vs.(33.97±2.38)mmHg],white blood cell count[(80.96±16.15)vs.(22.74±4.26)×10^(6)/ml],wet-to-dry weight ratio[(6.20±0.43)vs.(4.41±0.32)],Holfbauer score[(2.53±0.42)vs.(0.00±0.00)points],the levels of serum ROS[(232.05±31.72)vs.(112.47±16.84)mmol·L^(-1)],IL-18[(3.71±0.38)vs.(0.64±0.12)ng·ml^(-1)]and IL-6[(1.23±0.14)vs.(0.11±0.03)ng·ml^(-1)]in the model group were obviously higher,the arterial blood PaO_(2)[(65.75±5.09)vs.(98.12±8.25)mmHg],and the protein expression levels of lung tissue VEGFA[(0.49±0.07)vs.(1.31±0.22)],SDF-1[(0.41±0.09)vs.(1.28±0.15)]and CXCR4[(0.55±0.12)vs.(1.43±0.26)]were obviously lowered,the differences being statistically obvious(P<0.05).Compared with the model group and the ulinastatin+AMD3100 group,the arterial blood PaCO_(2),white blood cell count,wet-to-dry weight rati

关 键 词：血管内皮生长因子A/基质细胞衍生因子-1/CXC型趋化因子受体通路 乌司他丁 脑卒中相关性肺炎 保护作用 

分 类 号：R743.33[医药卫生—神经病学与精神病学]