【作者】 舒畅；

【导师】 王导新；

【作者基本信息】 重庆医科大学 ， 内科学， 2011， 硕士

【摘要】 目的观察晚期糖基化终末产物受体（RAGE）在不同程度急性肺损伤（ALI）大鼠血浆和肺泡灌洗液（BALF）中的变化,探讨RAGE在判断ALI严重程度方面的价值。方法1.建立不同程度肺损伤模型:用油酸-脂多糖二次打击方式复制ALI大鼠模型。30只SD大鼠随机分为3组:致伤低剂量组、致伤高剂量组、对照组,其中低剂量组:油酸0.1ml/kg、LPS 4mg/kg;致伤高剂量组:油酸0.15ml/kg、LPS 6mg/kg,对照组以生理盐水代替致伤剂。测量大鼠PaO₂、肺组织湿干重比值（W/D）、BALF蛋白含量、血浆和BALF肿瘤坏死因子-α（TNF-α）水平,并结合病理改变评价各组肺损伤程度。2. Western blot法检测各组大鼠血浆和BALF中RAGE相对含量,分析其与肺损伤程度之间的关系;检测血浆、BALF中血管内皮生长因子（VEGF）及血管生成素-2（Ang-2）浓度,用spearman秩相关分析上述指标与肺损伤程度的相关性,比较各组相关系数r值。结果1.两致伤组均出现PaO₂下降、肺组织W/D值及BALF中蛋白含量增加、血浆和BALF中TNF-α浓度升高,与对照组比较均有P<0.05,差异具有统计学意义,高剂量组上述改变更加明显,与低剂量组比较P<0.05,差异具有统计学意义;病理切片可见高剂量组肺损伤程度较低剂量组重。2.两致伤组血浆和BALF中RAGE水平升高,与对照组比较P<0.05,高剂量组BALF中RAGE水平与低剂量组比较P<0.05,具有统计学意义;而血浆中RAGE水平在低剂量组与高剂量组间差别无统计学意义。低剂量致伤组血浆VEGF、Ang-2浓度较对照组升高,高剂量组血浆VEGF、Ang-2浓度进一步升高,均有P<0.05;低剂量致伤组BALF中VEGF浓度较对照组下降,高剂量组BALF中VEGF浓度进一步下降,均有P<0.05;BALF中Ang-2浓度在各组间变化差异无统计学意义。BALF中RAGE水平及血浆中RAGE、VEGF、Ang-2含量与肺损伤程度均呈正相关,r值依次为0.943、0.667、0.863、0.877。结论1.给予梯度剂量的油酸-脂多糖二次打击,可以复制不同程度ALI大鼠模型。2.在油酸-脂多糖二次打击ALI大鼠模型中,随着肺损伤程度加重,BALF中RAGE水平呈上升趋势;BALF中RAGE水平及血浆中RAGE、VEGF、Ang-2与肺损伤程度均与肺损伤程度呈正相关,其中BALF中RAGE水平与肺损伤程度相关系数最高,能更好地反应ALI严重程度。更多还原

【Abstract】 ObjectiveTo investigate plasma and bronchoalveolar lavage fluid （BALF） level of receptor for advanced glycation end products （RAGE） in rat with different grade of experimental lung injury, exploring the value of RAGE in predicting the severity of ALI.Methods1. 30 Sprague-Dawley rats were randomly assigned into three groups （n=10）: low dose group （Oleic acid 0.1ml/kg and LPS 4mg/kg）, high dose group （Oleic acid 0.15ml/kg and LPS 6mg/kg） and control group （infused by sterile saline）. the PaO₂,wet/dry weight（W/D）of lung lobes, content of protein level in BALF, TNF-αcontent in plasma and BALF were examined, the change of lung pathology were observed also.2. Western blot was employed to detect the content of RAGE in plasma and BALF, analyzed the relationship of RAGE and the degree of lung injury;at the same time, the levels of vascular endothelial growth factor and angiopoietin-2 in plasma and BALF were also measured in order to analyze the relation of those biomarkers and the level of lung injury. The statistical analysis was carried out with Speraman’s correlation test.Results1. The different degrees of changes with PaO₂、protein and TNF-αin BALF、TNF-αin plasma and pathological were induced by each dose groups, the changes at high dose group were more remarkably.2. The content of RAGE in BALF and plasma increased in model groups than those of control group（P﹤0.05）, BALF RAGE in higher dose group elevated compared with that in other groups（P﹤0.05）.There was a tendency that increased expression level of VEGF and Ang-2 in plasma was associated with elevated level of lung injury. The speraman’s correlation coefficient of RAGE in BALF and RAGE、VEGF、Ang-2 in plasma were 0.943、0.667、0.863、0.877.Conclusion1.Different degrees of ALI in rats could induced by gradually increasing dose of OA and LPS.2.The level of RAGE in plasma and BALF increased in ALI, the increasing level of RAGE in BALF and RAGE、VEGF、Ang-2 in plasma were significantly correlated with the severity of lung injury, and the correlation coefficient of RAGE in BALF was higher than the others, determine the level of RAGE in BALF could help to judge the degree of lung injury.更多还原