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[摘要] 意图 评论PRA、AngⅡ在ALI/ARDS患者中的改变和含义。办法 测定ALI/ARDS和非ALI/ARDS患者血浆PRA和AngⅡ浓度,进行APACHEⅡ评分和LIS评分,核算病死率,进一步将患者按预后分组,进行比较和相关剖析,运用ROC曲线点评PRA和AngⅡ的确诊分辩度。成果 与非ALI/ ARDS组比较,ALI/ ARDS组血浆PRA和AngⅡ浓度显着增高(P <0.05),逝世组血浆PRA和AngⅡ浓度高于存活组(P <0.05)。PRA、AngⅡ与APACHEⅡ评分、LIS、乳酸(LAC)间均呈显着正相关。PRA在猜测ALI/ARDS方面有显着含义(AUC=0.705,P =0.001),AngⅡ对猜测ALI/ARDS也有显着含义(AUC=0.672, P=0.007)。在猜测ALI/ARDS方面,PRA、AngⅡ与LIS比较无显着差异(P =0.923,P =0.713)。 定论 ALI/ARDS患者血浆PRA和AngⅡ水平显着升高,两者在猜测ALI/ARDS和判别其预后方面均有重要含义,而AngⅡ在猜测ALI/ARDS中的特异度较高。
[关键词] 血浆肾素活性;血管严峻素Ⅱ;ALI/ARDS;确诊;预后
[中图分类号] R563[文献标识码] A[文章编号] 1673-9701(2014)18-0008-03
Changes of plasma renin activity and angiotensin Ⅱ level in and its significance
XIA Yanhuo1 ZHENG Xiaolei1 WANG Dan1 YUFangyou2 LIN Xifang1 PAN Jingye1
1.ICU, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; 2.Department of Laboratory, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
[Abstract] Objective To investigate the clinical significance and levels of plasma renin activity(PRA), Angiotensin(Ang) Ⅱ in ALI / ARDS patients. Methods The levels of PRA and AngⅡ, APACHE Ⅱ score, lung injury score(LIS), and mortality were analyzed in ALI/ARDS patients and non-ALI/ARDS group. After the patients were grouped according to prognosis, correlation analysis and ROC curve to evaluate diagnostic efficacy of PRA and AngⅡ were performed. Results Compared with non- ALI/ARDS group, the levels of PRA and AngⅡ were significantly increased in ALI/ARDS (P <0.05). In the death group, the levels of PRA and AngⅡwere higher than that of the survival group (P <0.05). It was significant positive correlation between APACHEⅡ score,LIS,lactic acid(LAC) and PRA, so as AngⅡ. In predicting ALI/ARDS, PRA was significant (AUC = 0.705, P = 0.001), so as AngⅡ(AUC = 0.672, P = 0.007). In predicting ALI/ARDS, there was no significant difference between PRA and LIS(P = 0.923), and also between AngⅡ and LIS(P = 0.713). Conclusion In ALI/ARDS patients, the levels of PRA and AngⅡwere significantly increased, and both could be used to predict ALI/ARDS and determine its prognosis, but AngⅡ had higher specificity in predicting ALI/ARDS.
[Key words] P lasma renin activity;Angiotensin Ⅱ;ALI/ARDS;Diagnosis;Prognosis
急性肺损害(acute lung njury,ALI)/急性呼吸困顿综合征(acute respiratory distress syndrome,ARDS) 是由肺表里致病因子导致的以进行性呼吸困顿、难治性低氧血症和弥漫性肺部滋润为首要特征的急性呼吸衰竭综合征。ALI 是 ARDS 的前期病变阶段。由于ARDS的病死率高,几十年来ALI一向成为国表里医学界研讨的热门。尽管现代医学在ALI/ARDS的知道以及生命支撑手法方面有了很大前进,但现在ARDS的病死率仍高达50%以上[1],成为 ICU患者逝世的首要病因之一。跟着研讨的深化,近年来发现血管严峻素与 ALI/ARDS有着密切联系[2,3]。本文旨在经过测定ALI/ARDS患者血浆肾素活性(plasma renin activity,PRA)和血管严峻素(Angiotensin,Ang II)的浓度,开始评论肾素-血管严峻素体系在ALI/ARDS中的改变和含义。
1目标与办法
1.1研讨目标
挑选2011年5月~2013年9月我院ICU病房收治的重症患者71例,其间男58例,女13例。一切入组患者根据是否契合1994年欧美联席会议提出的确诊规范分为ALI/ARDS组和非ALI/ARDS组。1994年欧美联席会议提出的确诊规范:①急性起病;②氧合指数(PaO2/FiO2)≤200mmHg[不论呼气末正压(PEEP)水平];③正位X线胸片显现双肺均有班片状暗影;④肺动脉嵌顿压≤18mmHg,或无左心房压力增高的临床根据。如PaO2/FiO2≤300mmHg且满意上述其它规范,则确诊为ALI。其间,ALI/ARDS组45例(男/女=39/6),平均年纪61.33岁,包含腹腔感染13例,肺部感染11例,败血症3例,急性重症胰腺炎9例,多发伤并肺伤害4例,严峻失血性休克3例,其他2例。非ALI/ARDS组26例(男/女=19/7),平均年纪64.57岁,包含急性左心衰12例,缓慢心功用不全伴脑梗死3例,缓慢阻塞性肺疾病9例,心肺复苏术后2例。对一切患者按预后分为逝世组和存活组,其间逝世组21例,平均年纪71.61岁;存活组50例,平均年纪60.10岁。
1.2 研讨办法
一切当选患者入科24h内取动静脉血生化检测和血气剖析,一切检测目标均由本院查验中心完结。对一切当选患者核算入科24h内APACHE II及LIS评分,核算ICU住院时刻和预后,核算病死率。一切患者均于入ICU后次日上午8时卧位抽取静脉血5 mL,离心分离血小板后保存在-40℃冰箱待检,用放射免疫法测定PRA、AngⅡ浓度,操作均由我院查验中心完结。
1.3 核算学办法
选用SPSS11.5软件进行剖析。计量材料进行正态查验,如正态分布,用均数±规范差(x±s)表明,选用两独立样本t查验,如非正态分布,用中位数(M)和四分位数距离(IQR)表明,选用两独立样本秩和查验(Mann-Whitney U查验);计数材料选用χ2查验;相关性剖析选用Pearson剖析;运用受试者作业特征(ROC)曲线点评PRA和AngⅡ在猜测ALI/ARDS中的价值,曲线下面积比较选用z查验。以P< 0.05 为有核算学含义。
2成果
2.1 ALI/ARDS组和非ALI/ARDS组临床材料及PRA、AngⅡ比较
ALI/ ARDS组患者年纪、住院天数、APACHEII评分、血乳酸水平与非ALI/ARDS组比较均无核算学含义(P>0.05)。与非ALIARDS组比较,ALI/ARDS组病死率显着增高(P=0.046);LIS评分显着升高(P=0.010);PaO2/FiO2显着下降(P=0.012)。ALI/ARDS组患者血浆PRA、AngⅡ水平显着高于非ALI/ARDS组(P=0.009,P =0.010)。见表1。
表1 ALI/ ARDS组和非ALI/ ARDS组临床材料及PRA、AngⅡ比较
2.2逝世组和存活组临床材料和PRA、AngⅡ比较
与存活组比较,逝世组患者年纪显着偏大、APACHEⅡ评分和LIS评分显着增高(P﹤0.05);逝世组患者血浆LAC、PRA和AngⅡ显着升高(P﹤0.05)。见表2。
表2 逝世组和存活组临床材料和PRA、AngⅡ比较
2.3 血浆PRA、AngⅡ与LIS、APACHEⅡ评分、LAC间的相关剖析
PRA与 AngⅡ呈显着正相关(r=0.827,P=0.000),PRA、AngⅡ与LIS、APACHEⅡ评分、LAC间也呈显着正相关。见表3。
表3 血浆PRA、AngII和LIS、APACHEⅡ评分、LAC之间相关剖析
2.4 PRA、AngⅡ的确诊价值验证
ROC曲线剖析显现,PRA在猜测ALI/ARDS方面有显着含义[曲线下面积(AUC)=0.705,95% CI 0.585~0.807,P=0.001],且PRA﹥1.21μg/(L·h)时,猜测ALI/ARDS确诊的灵敏度为66.67%,特异度为73.08%,阳性猜测率为81.1%,阴性猜测率为55.9%。AngⅡ对猜测ALI/ARD也有显着含义(AUC=0.672,95%CI 0.551~0.779,P=0.007),AngⅡ﹥50.42 ng/L时,猜测ALI/ARDS确诊的灵敏度和特异度分别为44.44%和88.46%,阳性猜测率为87.0%,阴性猜测率为47.9%。在猜测ALI/ARDS方面,AngⅡ与LIS比较无显着差异(z=0.368 , P =0.713),相同PRA与LIS比较也无显着差异(z=0.096 , P =0.923)。见图1。
图1 AngⅡ与PRA猜测ALI/ARDS状况
3评论
近年来,人们发现 RAS不只在心血管疾病中起效果,并且它与 ARDS密切相关。动物试验发现,打针LPS仿制肺损害模型后,动物血浆Ang Ⅱ显着升高,到达正常对照组8倍以上,且AngⅡ能导致肺通透性添加,引发肺水肿。给予外源性重组ACE 2后,血浆Ang Ⅱ显着下降、TNF-α削减,炎症损害减轻,肺AngⅡ含量升高与肺损害程度和机械通气时刻延伸相关[4,5,6]。本研讨发现,ALI/ARDS患者血浆PRA、AngⅡ显着高于非ALI/ARDS患者,ALI/ARDS患者病死率(37.78%)显着高于非ALI/ARDS患者(15.38%),而逝世组患者血浆PRA、AngⅡ显着高于存活组,提示ALI/ARDS患者体内存在RAS激活,导致血浆PRA、AngⅡ显着升高,而AngⅡ升高使肺血管通透性添加,然后加剧了ALI/ARDS患者的病况。本研讨的相关剖析成果显现,血浆PRA与APACHEⅡ、LAC呈显着正相关,而AngⅡ与APACHEⅡ、LAC也呈显着正相关。咱们知道,APACHEⅡ是现在世界上广泛运用的危重患者评分体系,该体系在评价患者病况危重程度和预后方面均有重要效果[7];而近年来的研讨证明,血LAC水平是严峻感染中又一重要的判别病况程度和预后的目标[8]。血浆PRA、AngⅡ浓度与APACHEⅡ、LAC呈显着正相关,提示血浆PRA、AngⅡ浓度对患者病况严峻程度和预后判别有重要含义。这与Doerschug等的报导相一致,该报导称在脓毒症患者中激活的RAS介导微血管功用失调,PRA和AngⅡ水平与器官功用衰竭程度显着相关,也与患者预后相关[9]。
肺损害评分(lung injury score, LIS)体系由Murray等在1988年提出,该体系对肺损害的规模和严峻程度进行分级,从胸片、低氧血症、PEEP和呼吸体系顺应性等四方面进行评分。Owens等研讨报导LIS可以对肺损害的程度进行比较和半定量,也可对疾病的发展进程进行接连评价,评分体系和胸部扫描所显现的病变规模高度相符,也与肺泡渗出的严峻程度高度相符,阐明LIS体系在ALI/ARDS确诊方面有较好的价值[10]。本研讨相关剖析发现,PRA、AngⅡ与LIS具有较好的相关性,动物试验也证明内毒素肺损害大鼠血浆AngⅡ水平与急性肺损害程度呈正相关[11]。咱们经过ROC曲线下面积比较,成果显现PRA和AngⅡ在猜测ALI/ARDS的准确性方面与LIS比较无显着差异(P>0.05),提示PRA、AngⅡ在猜测ALI/ARD上与LIS评分的确诊价值适当。进一步验证PRA、AngⅡ在ALI/ARDS中的确诊价值,PRA在猜测ALI/ARDS方面有显着含义[曲线下面积(AUC)=0.705, v=0.001],且PRA﹥1.21μg/(L·h)时,猜测ALI/ARDS确诊的灵敏度为66.67%,特异度为73.08%;AngⅡ对猜测ALI/ARD也有显着含义(AUC=0.672, P=0.007),AngⅡ﹥50.42 ng/L时,猜测ALI/ARDS确诊的特异度较好,为88.46%,但灵敏度(44.44%)一般,提示PRA和AngⅡ在猜测ALI/ARDS上均有重要含义,这为PRA、AngⅡ用于ALI/ARDS前期确诊供给了临床根据。
综上所述,ALI/ARDS患者激活了RAS,导致血浆PRA和AngⅡ水平显着升高, PRA和AngⅡ水平对病况严峻程度和预后判别均有重要效果,并且二者在猜测ALI/ARDS中的准确性均较好,其间AngⅡ在猜测ALI/ARDS中特异度较高。咱们知道RAS激活在休克患者中起到安稳血流动力学效果,那么ALI/ARDS患者RAS激活是否由于这些危重患者存在休克而激活了RAS体系,或者是RAS体系过度激活才导致患者呈现ALI/ARDS,需求进一步研讨和评论。
[参考文献]
[1]Tsushima K, King LS, Aggarwal NR, et al. Acute lung injury review[J]. Inten Med,2009,48:621-630.
[2]Zhuang JJ,LI XP,Uhal BD,et al. Poptosis-dependent acute pulmonary injury after intratracheal instillation of angiotensin Ⅱ[J]. Acta Physiologica Sinica,2008,60(6): 715- 722.
[3]Kaparianos A,Argyropoulou E. Local renin-angiotensin Ⅱ systems,angiotensin-converting enzyme and its homologue ACE2:Their potential role in the pathogenesis of chronic obstructive pulmonary diseases, pulmonary hypertension and acute respiratory distress syndrome[J]. Curr Med Chem,2011,8(23):3506-3515.
[4]Treml B,Neu N,Kleinsmer A,et al. Recombinant angiotensin converting enzyme 2 improves pulmonary blood flow andoxygenation in lipopolysaccharide-induced lung injury in piglets[J]. Crit Care Med,2010,38:596-601.
[5]朱英,邱海波,杨毅,等. 血管严峻素Ⅱ诱导急性肺损害大鼠血管严峻素Ⅱ 2型受体表达调控的研讨[J]. 我国危重病急救医学,2008,20(10):585-587.
[6]朱宏飞,冯丹,姚尚龙,等. 机械通气肺损害时肾素-血管严峻素体系激活的试验研讨[J]. 华中科技大学学报(医学版),2010,39(2):147-151.
[7]Knaus WA, Draper EA, Wagner DP, et al. APACHE Ⅱ: A severity of disease classification system[J]. Crit Care Med,1985,13(10):818-829.
[8]中华医学会重症医学分会.成人严峻感染与感染性休克血流动力学监测与支撑攻略(草案)[J]. 我国危重病急救医学,2007,19(3):129-133.
[9]Doerschug KC, Delsing AS, Schmidt GA,et al.Renin-angiotensin system activation correlates with microvascular dysfunction in a prospective cohort study of clinical sepsis [J]. Crit Care, 2010,14(1):R24-R32.
[10]Owens CM, Evans TW, Keogh BF,et al. Computed tomography in established adult respiratory distress syndrome correlation with lung injury score[J]. Chest,1994, 106(6):1815-1821.
[11]缪李丽,骆玲,王导新. AngⅡ在大鼠内毒素性急性肺损害中的效果[J]. 细胞与分子免疫学杂志, 2009, 25(11):1005-1007.
(收稿日期:2013-12-16)
[参考文献]
[1]Tsushima K, King LS, Aggarwal NR, et al. Acute lung injury review[J]. Inten Med,2009,48:621-630.
[2]Zhuang JJ,LI XP,Uhal BD,et al. Poptosis-dependent acute pulmonary injury after intratracheal instillation of angiotensin Ⅱ[J]. Acta Physiologica Sinica,2008,60(6): 715- 722.
[3]Kaparianos A,Argyropoulou E. Local renin-angiotensin Ⅱ systems,angiotensin-converting enzyme and its homologue ACE2:Their potential role in the pathogenesis of chronic obstructive pulmonary diseases, pulmonary hypertension and acute respiratory distress syndrome[J]. Curr Med Chem,2011,8(23):3506-3515.
[4]Treml B,Neu N,Kleinsmer A,et al. Recombinant angiotensin converting enzyme 2 improves pulmonary blood flow andoxygenation in lipopolysaccharide-induced lung injury in piglets[J]. Crit Care Med,2010,38:596-601.
[5]朱英,邱海波,杨毅,等. 血管严峻素Ⅱ诱导急性肺损害大鼠血管严峻素Ⅱ 2型受体表达调控的研讨[J]. 我国危重病急救医学,2008,20(10):585-587.
[6]朱宏飞,冯丹,姚尚龙,等. 机械通气肺损害时肾素-血管严峻素体系激活的试验研讨[J]. 华中科技大学学报(医学版),2010,39(2):147-151.
[7]Knaus WA, Draper EA, Wagner DP, et al. APACHE Ⅱ: A severity of disease classification system[J]. Crit Care Med,1985,13(10):818-829.
[8]中华医学会重症医学分会.成人严峻感染与感染性休克血流动力学监测与支撑攻略(草案)[J]. 我国危重病急救医学,2007,19(3):129-133.
[9]Doerschug KC, Delsing AS, Schmidt GA,et al.Renin-angiotensin system activation correlates with microvascular dysfunction in a prospective cohort study of clinical sepsis [J]. Crit Care, 2010,14(1):R24-R32.
[10]Owens CM, Evans TW, Keogh BF,et al. Computed tomography in established adult respiratory distress syndrome correlation with lung injury score[J]. Chest,1994, 106(6):1815-1821.
[11]缪李丽,骆玲,王导新. AngⅡ在大鼠内毒素性急性肺损害中的效果[J]. 细胞与分子免疫学杂志, 2009, 25(11):1005-1007.
(收稿日期:2013-12-16)
[参考文献]
[1]Tsushima K, King LS, Aggarwal NR, et al. Acute lung injury review[J]. Inten Med,2009,48:621-630.
[2]Zhuang JJ,LI XP,Uhal BD,et al. Poptosis-dependent acute pulmonary injury after intratracheal instillation of angiotensin Ⅱ[J]. Acta Physiologica Sinica,2008,60(6): 715- 722.
[3]Kaparianos A,Argyropoulou E. Local renin-angiotensin Ⅱ systems,angiotensin-converting enzyme and its homologue ACE2:Their potential role in the pathogenesis of chronic obstructive pulmonary diseases, pulmonary hypertension and acute respiratory distress syndrome[J]. Curr Med Chem,2011,8(23):3506-3515.
[4]Treml B,Neu N,Kleinsmer A,et al. Recombinant angiotensin converting enzyme 2 improves pulmonary blood flow andoxygenation in lipopolysaccharide-induced lung injury in piglets[J]. Crit Care Med,2010,38:596-601.
[5]朱英,邱海波,杨毅,等. 血管严峻素Ⅱ诱导急性肺损害大鼠血管严峻素Ⅱ 2型受体表达调控的研讨[J]. 我国危重病急救医学,2008,20(10):585-587.
[6]朱宏飞,冯丹,姚尚龙,等. 机械通气肺损害时肾素-血管严峻素体系激活的试验研讨[J]. 华中科技大学学报(医学版),2010,39(2):147-151.
[7]Knaus WA, Draper EA, Wagner DP, et al. APACHE Ⅱ: A severity of disease classification system[J]. Crit Care Med,1985,13(10):818-829.
[8]中华医学会重症医学分会.成人严峻感染与感染性休克血流动力学监测与支撑攻略(草案)[J]. 我国危重病急救医学,2007,19(3):129-133.
[9]Doerschug KC, Delsing AS, Schmidt GA,et al.Renin-angiotensin system activation correlates with microvascular dysfunction in a prospective cohort study of clinical sepsis [J]. Crit Care, 2010,14(1):R24-R32.
[10]Owens CM, Evans TW, Keogh BF,et al. Computed tomography in established adult respiratory distress syndrome correlation with lung injury score[J]. Chest,1994, 106(6):1815-1821.
[11]缪李丽,骆玲,王导新. AngⅡ在大鼠内毒素性急性肺损害中的效果[J]. 细胞与分子免疫学杂志, 2009, 25(11):1005-1007.
(收稿日期:2013-12-16)












