【作者】 王锐；

【导师】 李培杰；

【作者基本信息】 兰州大学 ， 临床医学·急诊医学， 2017， 硕士

【摘要】 目的:本实验通过测定严重创伤后患者不同时间点瓜氨酸、I-FABP、内毒素及PCT水平,观察严重创伤后患者肠粘膜损伤与内毒素移位程度,分析生物学标志物相互之间及与创伤后AGI之间的相关性,并纳入SOFA评分、APACHEⅡ评分,探讨肠粘膜损伤在MODS病理变化过程中作用。方法:采用前瞻性研究方法,纳入2015年8月至2016年12月入住兰州大学第二医院内科ICU创伤后24h内首诊我院的患者(18岁<年龄<80岁)。排除闭合及开放性腹部创伤、急慢性肠道疾病及胃肠道手术史患者,存在急慢性肾脏、肝脏疾病患者,可疑感染患者,妊娠期妇女。根据创伤严重程度评分ISS分为轻度创伤组(ISS<16),重度创伤组(ISS≥16)。根据入院72h内是否发生急性胃肠损伤分为AGI组,AGI0组,根据2012年欧洲危重病医学会对AGI分级指南,对AGI组分为3个亚组,A GI1组,AGI2组,AGI3组。选择同期兰州大学第二医院健康体检者作为正常对照组。收集患者基本临床资料及AGI分级,采集入院第1天及第3天静脉血标本,用于测量瓜氨酸、I-FABP、内毒素及PCT水平。结果:1.第1天重伤组、轻伤组瓜氨酸水平较对照组均显著降低(P<0.01或P<0.05),且重伤组显著低于轻伤组(P<0.01),第3天各组瓜氨酸水平进一步下降(P均<0.01),重伤组仍显著低于轻伤组(P<0.01)。第1天AGI3组中瓜氨酸水平较AGI0组、AGI1组、AGI2组显著降低(P<0.01或P<0.05),AGI2、AGI1组也较AGI0组显著下降(P<0.01或P<0.05)。第3天各组瓜氨酸水平均进一步下降(P<均0.01),各亚组间分级越高,瓜氨酸水平下降越显著(P<0.01或P<0.05)。瓜氨酸水平与AGI严重程度呈负相关。瓜氨酸对严重创伤后AGI预测的ROC曲线下面积为0.88,最佳界值为19.07umol/L,此时敏感性为87.10%,特异性为76.47%.2.第1天重伤组、轻伤组I-FABP水平较对照组显著升高(P均<0.01),且重伤组显著高于轻伤组(P<0.01)第3天各组I-FABP水平进一步下降(P均<0.01),重伤组仍高于轻伤组(P<0.05)。第1天AGI3组中I-FABP水平较AGI0组、AGI1组、AGI2组显著升高(P<0.01或P<0.05),AGI2组也较AGI0组显著升高(P<0.01)。第3天AGI0组、AGI2组、AGI3组I-FABP水平均进一步下降(P<均0.01),AGI3组、AG2组I-FABP水平仍显著高于AGI0组(P<0.01或P<0.05)。I-FABP与AGI严重程度呈正相关。I-FABP对严重创伤后AGI预测的ROC曲线下面积为0.84,最佳界值为1657pg/ml,此时敏感性为90.32%,特异性为64.71%。3.第1天重伤组、轻伤组内毒素水平较对照组显著升高(P均<0.01),且重伤组显著高于轻伤组(P<0.01)第3天各组内毒素水平较第1天变化不明显,差异不具有统计学意义(P>0.05),但重伤组仍显著高于轻伤组(P<0.01)。第1天AGI3组中内毒素水平较AGI0组、AGI1组、AGI2组显著升高(P<0.01或P<0.05),AGI2组也较AGI0、AGI1组显著升高(P<0.01或P<0.05),AGI1组较AGI0组升高(P<0.05)。第3天仅AGI0组内毒素水平进一步下降(P<0.05),AGI3组内毒素水平仍显著高于AGI0、AGI1组(P<0.01),AGI2组仍显著高于AGI0组、AGI1组(P<0.01或P<0.05),AGI1组水平仍显著高于AGI0组(P<0.05)。内毒素水平与AGI严重程度呈正相关。内毒素对严重创伤后AGI预测的ROC曲线下面积为0.90,最佳界值为0.234EU/ml,此时敏感性为90.32%,特异性为82.35%。4.第1天重伤组PCT水平较对照组、轻伤组显著升高(P<0.01或P<0.05),第3天各组PCT水平较第1天差异不具有统计学意义(P>0.05),但重伤组仍高于正常组(P<0.05)。第1天仅AGI3组中PCT水平较AGI0组、AGI1组、AGI2组显著升高(P均<0.01),第3天其水平与第1天相比差异无统计学意义(P>0.05),但AGI3组PCT水平仍高于AGI1、AGI0组(P<0.01或P<0.05),AGI2组高于AGI0组(P<0.01)。5.创伤后瓜氨酸水平与I-FABP、内毒素、PCT、APACHEⅡ评分、SOFA评分呈明显负相关,与I-FABP、内毒素、PCT、APACHEⅡ评分、SOFA评分之间存在明显正相关。入院后72h内手术组第3天的I-FABP水平较非手术组显著升高,存在正相关。结论:创伤后早期血清I-FABP、内毒素、PCT水平显著升高,其水平变化均与创伤严重程度和AGI严重程度程度有明显的正相关,血清瓜氨酸水平显著降低,其水平变化与创伤严重程度和AGI严重程度程度有明显的负相关;APACHEⅡ评分、SOFA评分与瓜氨酸水平呈明显负相关,与I-FABP、内毒素、PCT之间存在明显正相关,瓜氨酸、I-FABP、内毒素、PCT相关之间存在明显相关性;瓜氨酸、I-FABP、内毒素水平可以作为是预测创伤后早期肠粘膜损伤的潜在生物学标志物。更多还原

【Abstract】 Objective:Through measuring the levels of citrulline,I-FABP,endotoxin and PCT at different time after severe trauma,the aim of the study is to observe the degree of intestinal mucosal injury and endotoxin translocation,to to analyze the relationship between the biological markers I each other and the clinical manifestation of AGI,and to to explore the role of intestinal mucosal lesions in the pathogenesis of MODS combined with SOFA score,APACHEⅡ score.Methods:Using prospective research methods,we choose the severely traumatic patients who had hospitalized at the MICU in the Sencond Hospital of Lanzhou University during August 2015 to December 2016,and eliminated patients with gastrointestinal tract trauma,intestinal resection and chronic intestinal disease,acute and chronic kidney disease,acute and chronic kidney liver diseases.The patients who was suspected infection and the pregnant women were also eliminated.Forty-eight patients with severe trauma were divided into minor trauma(ISS<16)group and severe trauma(ISS≥16)group according to ISS and divided into AGI group and non-AGI group based on with or without AGI.AGI group were divided into three subgroups,including AGI1 group,AGI2 group,AGI3 group.We select the people who came the second hospital in Lanzhou University for healthy physical examination as a normal control group during the time of the sdudy.The basic clinical data and AGI grade were collected.The venous blood samples were collected for the measurement of citrulline,I-FABP,endotoxin and PCT on the 1st and 3rd day of admissionResults:1.Compared to the nomal control group,the citrulline levels in the minor trauma group and the severe trauma group were both reduced obviously at day 1 after trauma(P<0.01 or P<0.05),with lower level in the severe traumatic group than that in the minor trauma group(p<0.0 1).The citrulline levels in both group decreased gradually at day 3.The severe group was still significantly lower than that in the minor trauma group(P <0.01).Compared to the AGI0,AGI1 and AGI2 group,the I-FABP levels in the AGI3 group reduced obviously at day 1 after trauma(P <0.01 or P<0.05.),and which was similar in the AGI2 group compared to the AGI0 and AGI 1group(P <0.01 or P<0.05).The citrulline levels in all subgroup decreased gradually at day 3(P <0.01).The higher the grade of each subgroup,the more the decrease of citrulline levels(P <0.01 or P <0.05),and the area under the ROC curve was 0.88,the best cutoff was 19.07 umol / L,the sensitivity was 87.10%,the specificity was 76.47% for prediction of acute gastrointestinal injury after severe trauma.2.Compared to the nomal control group,the I-FABP levels in the minor trauma group and the severe trauma group were both increased obviously at day 1 after trauma(P <0.01),with higher level in the severe traumatic group than that in the minor trauma group(p<0.01).The I-FABP levels in both group decreased gradually at day 3.The severe group was still significantly higher than that in the minor trauma group(P <0.05).Compared to the AGI0,AGI1 and AGI2 group,the citrulline levels in the AGI3 group increased obviously at day 1 after trauma(P <0.01 or P<0.05),and which was similar in the AGI2 group compared to the AGI0 group(P <0.01).The I-FABp level in AGI0,AGI2 and AGI 3 group decreased gradually at day 3(p<0.01).With higher level in the AGI 2 and AGI3 group than that in the AGI 0 group((p <0.01 or p <0.05).The level of I-FABP was positively correlated with AGI severity,and the area under the ROC curve was 0.84,the best cutoff was 1657pg/ml,the sensitivity was 90.32%,the specificity was 64.71% for prediction of acute gastrointestinal injury after severe trauma.3.Compared to the nomal control group,the endotoxin levels in the minor trauma group and the severe trauma group were both increased obviously at day 1 after trauma(P <0.01),with higher level in the severe traumatic group than that in the minor trauma group(P <0.01).The endotoxin levels in both group did not change obvious at day 3(P>0.05).The severe group was still significantly higher than that in the minor trauma group(P <0.05).Compared to the AGI 0,AGI1 and AGI2 group,the endotoxin levels in the AGI3 group increased obviously at day 1 after trauma(P <0.01 or P<0.05),and which was similar in the AGI2 group compared to the AGI0 and AGI 1 group(P <0.01 or P<0.05),in the AGI1 group compared to the AGI0 group(P<0.05)The endotoxin level only in the AGI0 decreased gradually at day 3(P <0.05).With higher level in the AGI3 group than that in the AGI0 and AGI1 group((P <0.01 or P <0.05),in the AGI2 group than in the AGI1 and AGI0 group,in the AGI1 than in the AGI0.The level of endotoxin was positively correlated with AGI severity,and the area under the ROC curve was 0.90,the best cutoff was 0.234EU/ml,the sensitivity was 90.32%,the specificity was 82.35% for prediction of acute gastrointestinal injury after severe trauma.4.Compared to the nomal control group,the PCT levels in the minor trauma group and the severe trauma group were both increased obviously at day 1 after trauma(P <0.01 or P<0.05).The endotoxin levels in both group did not change obvious at day 3(P>0.05).The severe group was still significantly higher than that in the minor trauma group(P <0.05).Compared to the AGI0,AGI1 and AG2 group,the PCT levels only in the AGI3 group increased obviously at day 1 after trauma(P <0.01).The pCT level among all group did not change obvious at day 3(P>0.05).With higher level in the AGI3 group than that in the AGI0 and AGI1 group((P <0.01 or P <0.05),in the AGI2 group than in the AGI0 group.The level of PCT was positively correlated with AGI severity.5.There was a significant negative correlation between the level of citrulline and the levels of I-FABP,endotoxin,PCT,APACHEⅡ score and SOFA score on day 1,day 3.The levels of I-FABP,endotoxin,PCT,APACHEⅡ score,SOFA scores were positively correlated with each other on day 1,day 3.The same result is obtained by combining the indicators of day 1and day 3.The level of I-FABP in the operation group was significantly higher than that in the non-operation group at 72 hours after admission.Conlusion:The levels of citrulline,I-FABP,endotoxin and PCT were significantly increased in the early stage of trauma,and the changes of the levels were positively correlated to the severity of trauma and the severity of AGI,which of citrulline showed the opposite change.There was a significant negative correlation between APACHEII score and SOFA score and the level of citrulline,and which was positive between APACHEⅡ score and SOFA score and the levels of I-FABP,endotoxin,PCT.The levels of citrulline,I-FABP,endotoxin,PCT,were positively correlated with each other.Citrulline,I-FABP endotoxin levels can be used as a potential biomarker for predicting early AGI in patients with severe trauma.更多还原