地塞米松对大鼠光气急性肺损伤血管生成素-1、2的影响

目的 探讨地塞米松对大鼠光气急性肺损伤(ALI)血管生成素-1、2(Ang-1,2)表达的影响.方法 采用大鼠光气吸入性肺损伤动物模型.36只SD大鼠随机(随机数字法)分为3组:正常对照组(吸入与光气染毒组同等流量的空气)、光气染毒组(吸入8.33 mg/L纯度为100％的光气5min)、地塞米松处理组(尾静脉注入2.5 mg/kg地塞米松1h后,吸入同等剂量的光气).染毒2h后收集支气管肺泡灌洗液(BALF)测定中性粒细胞细胞数、蛋白含量和肺湿/干质量比(W/D).采用双抗体夹心酶标免疫分析法(ELISA法)测定各组血清和BALF中Ang-1,2水平.RT-PCR法对肺脏组织中Ang-1,2和Tie-2mRNA的水平进行半定量研究.Western blot技术检测肺脏组织中Ang-1,2和Tie-2蛋白含量.结果 与正常对照组比较,光气染毒组肺W/D、BALF中中性粒细胞数和蛋白含量明显升高,差异具有统计学意义(P＜0.01);与光气染毒组比较,地塞米松处理组的肺W/D、BALF中中性粒细胞数和蛋白含量明显降低,差异具有统计学意义(P＜0.01).与正常对照组比较,光气染毒组血清、BALF及肺组织中Ang-1和Tie-2表达明显下降,差异具有统计学意义(P＜0.01);与光气染毒组比较,地塞米松处理组Ang-1和Tie-2表达明显升高,差异具有统计学意义(P＜0.01).与正常对照组比较,光气染毒组血清、BALF及肺组织中Ang-2表达明显升高,差异具有统计学意义(P＜0.01);与光气染毒组比较,地塞米松处理组Ang-2表达明显下降,差异具有统计学意义(P ＜0.05,P＜0.01).结论 地塞米松可能通过抑制Ang-2表达并促进Ang-1和Tie-2表达来有效地保护大鼠光气吸入性急性肺损伤.     

血管生成素2在脓毒症和急性肺损伤/急性呼吸窘迫综合征中的作用

脓毒症引起的急性肺损伤/急性呼吸窘迫综合征(ALI/ARDS)、脓毒性休克及多器官功能障碍综合征(MODS)是其重要致死原因[1];而伴有急性器官功能障碍的严重脓毒症是目前重症监护病房(ICU)患者死亡的主要原因[2].     

输血相关急性肺损伤的研究进展

输血相关急性肺损伤(TRALI)是一种可以致命的输血并发症,主要表现为在输血后6 h内出现急性呼吸困难、双肺水肿、低血压、发热和低氧血症等。多种血液制品均可诱发TRALI,包括全血、红细胞、血小板、新鲜冷冻血浆、粒细胞、冷沉淀及免疫球蛋白(IVIG)。但是目前还没有关于输注清蛋白可以导致TRALI的报道。输注总量与TRALI发生的关系不明显,极少量(10 mL)血液制品即可引发TRALI。     

急性心肌梗死大鼠心肌组织血管生成素2表达与心肌梗死面积的关系

目的 观察急性心肌梗死(acute myocardial infarction, AMI)大鼠心肌组织血管生成素2(angiopoietin 2, Ang2)表达变化,探讨其与心肌梗死面积的关系。方法 SPF级SD雄性大鼠95只,随机选择55只结扎冠状动脉左前降支制备AMI模型,40只造模成功者为模型组;余40只大鼠为假手术组,只开胸,不结扎冠状动脉。2组分别于造模1、2周时行超声心动图检查,测量左心室舒张末期内径(left ventricular end-diastolic dimension, LVEDD)、左心室收缩末期内径(left ventricular end-systolic dimension, LVESD)、左心室短轴缩短率(left ventricular fractional shortening, LVFS)、左室射血分数(left ventricular ejection fraction, LVEF);然后处死大鼠取心脏,采用TTC染色法测定心肌梗死面积百分比,采用免疫组织化学SP法检测心肌组织Ang2阳性表达率,采用Western blot法检测心肌组织A...     

输血相关急性肺损伤研究进展

输血相关急性肺损伤(transfusion related acute lung injury,TRALI)系指输入血液、血浆及相关制品6h内急性发作的临床综合症[1],主要表现为肺部受损的症状,是一种严重的非传染性的输血并发症,发作快,预后不佳,致死率可达6％～10％[2-4].TRALI目前已成为输血医学界关注和研究的焦点,但仍有诸多机制尚不明确.笔者从其发病机制、临床表现及诊断、治疗及预防等方面综述如下.1发病机制1.1抗原抗体学说抗原抗体学说的主要观点认为,献血者血液中存在有抗受体细胞的抗体,而受体血液中也可存在抗供体细胞的抗体,输血后双方抗原抗体相结合后发生一系列的反应从而导致肺损伤[3].临床上最常见的主要是供者血液成分中含有抗对受血者白细胞抗原的抗体,而受血者的白细胞抗体与供血者的白细胞抗原发生反应则较少见.抗原抗体发生反应后,抗体可直接黏附并损伤受血者肺部内皮细胞或肺泡上皮细胞,从而增加肺毛细血管的通透性,最终导致肺水肿的发生;此外,Nishimura等[5]证实抗原抗体反应还能激活补体,产生的补体片段可促使肺部毛细血管渗漏,迅速加重急性肺损伤.但并不是所有的TRALI患者都表现为抗原抗体阳性,说明TRALI还存在其他的发病机制.     

血管生成素2在评估急性呼吸窘迫综合征中的临床价值

目的 探讨血清中血管生成素-1、2及白介素-8在评估ARDS中的临床价值.方法 筛选2012年1月至2013年7月湖南省人民医院急诊重症监护病房(EICU)的危重病患者283例,根据其病情是否发展为ARDS,分为非ARDS组(251例)和ARDS组(32例),并随访60 d,根据是否死亡,将非ARDS组和ARDS组再分为死亡组及存活组,采用ELISA测定其入院时Ang-1、2及IL-8的血清质量浓度,并对各组之间差异是否有统计学意义进行统计学及ROC曲线分析.结果 ARDS组患者EICU住院天数、机械通气时间、APACHEⅡ评分、血清血管生成素-2及IL-8水平显著高于非ARDS组患者,而Ang-1血清浓度显著低于非ARDS组患者.ARDS死亡组患者Ang-2、IL-8血清质量浓度显著高于非ARDS存活组及非ARDS死亡组,且ARDS死亡组患者血清Ang-2质量浓度显著高于ARDS存活组,其他各组之间比较差异无统计学意义.ROC曲线分析显示Ang-2具有最好的诊断效率,其诊断ARDS及预测ARDS死亡事件的曲线下面积分别为0.907和0.899,其灵敏度和特异性分别为0.969和0.725,0.907和0.882.结论 Ang-2是临床ARDS早期诊断及预后评估非常有价值的指标.     

输血相关急性肺损伤的预防

输血相关的急性肺损伤(transfusion related acute lung in jury,TRALI)是输血并发症.美国食品药品管理局报告,最近几年TRALI引起的死亡率已位居输血不良反应首位,但仍有许多问题尚未弄清[1].2004年4月加拿大血液服务机构和Hémaentitled召开了主题为"关于TRALI认识"的研讨会,研讨的问题范围包括如何定义TRALI TRALI的病理机制、对具有潜在TRALI风险的献血者是否排除其献血或延缓其献血、是否有能够排除具有潜在TRALI风险献血者的实验室筛查试验.     

输血相关的急性肺损伤

输血是一种异体移植。除抢救生命外，尽可能不输血。输血可发生多种反应，除可传播疾病外，有2％～10％的病人可发生轻重不等的不良反应，世界上输血死亡率可达0．5％～1．0％。但对于输血相关的急性肺损伤很多人却知之甚少。输血相关的急性肺损伤（TRALI）是指输血过程中或输血后6h内发生的一种急性呼吸窘迫综合征。其病理生理、临床表现及治疗与其它原因所致的急性呼吸窘迫综合征相似，     

血管生成素-2与急性胰腺炎关系的研究进展

血管生成素(Ang)是一种新的内皮生长因子家族,在血管生成及血管稳定性方面起着重要作用。Ang-2是Ang-1的天然拮抗剂,具有破坏血管壁稳定和促进新生血管形成的作用。本文对Ang-2的生物学特性及其在炎症和急性胰腺炎发病机制中的相关研究进展加以综述。     

输血相关急性肺损伤大鼠模型建立及肺组织病理研究

目的 建立输注人类血浆大鼠输血相关急性肺损伤(TRALI)模型并分析其肺组织病理特点.方法 将分离存储21 d后人AB型全血中的血浆,经静脉输注给经脂多糖预处理后的雄性Sprague Dawley大鼠,建立TRALI 模型;分析大鼠肺组织病理及湿干比变化.结果 输注了从存储后人全血中分离血浆的大鼠成功建立起TRALI模型,大鼠肺组织出现肺泡间隔增厚、肺泡内纤维蛋白浸润、肺泡内出血、支气管壁增厚等病理变化,肺组织湿干比增高等改变.结论 所建立的输注(人)存储后全血中分离的血浆的TRALI大鼠模型具有可行性、实用性与稳定性等特点,为诊断和治疗TRALI提供了实验基础.     

重组白细胞介素-10/Fc融合蛋白对内毒素诱导急性肺损伤小鼠的实验干预作用

目的 探讨重组白细胞介素-10(rIL-10)/Fc融合蛋白对内毒素诱导的急性肺损伤(ALl)小鼠炎症调控作用及其机制.方法 向气管内注射脂多糖(LPS)制成ALl动物模型;rIL-10/Fc融合蛋白采用腹腔内给药方式.132只小鼠被随机均分为正常对照组、rIL-10/Fc对照组、ALl模型组、rIL-10/Fc治疗组.每组选择25只小鼠观察24 h存活率;其余用于检测支气管肺泡灌洗液(BALF)中自细胞数量,肿瘤坏死因子-a(TNF-a)和IL-1β水平,以及肺组织髓过氧化物酶(MPO)活性、肺组织湿/干重(W/D)比值;光镜下观察肺组织病理学改变.结果 注射LPS后4 h可引起BALF中TNF-a和IL-1β显著升高(P均＜0.01),rIL-10/Fc治疗组较ALI模型组有所降低,但差异无统计学意义;但在8 h和12 h,rIL-10/Fc融合蛋白能显著抑制BALF中TNF-a产生,在12 h抑制IL-1β产生;并明显改善LPS注射24 h后实验动物的存活率(P＜0.01).rIL-10/Fc对LPS诱导的ALI小鼠BALF中白细胞数量、肺组织MPO活性、肺组织W/D比值无显著改变.注射LPS 24 h后,肺组织出现了明显的炎性改变,但在rlL-10/Fc融合蛋白干预后没有出现显著的差异.结论 rIL-10/Fc融合蛋白能显著抑制LPS诱导的ALI小鼠肺促炎细胞因子产生,改善预后.     

HLA class II antibodies in transfusion-related acute lung injury

BACKGROUND: Transfusion-related acute lung injury (TRALI) is a serious, sometimes fatal, complication of transfusion. Granulocyte and HLA class I antibodies present in blood donors have been associated with TRALI. HLA class II antibodies have recently been described in a few cases of TRALI. STUDY DESIGN AND METHODS: Donors involved in TRALI reactions reported to a blood center over an 18-month period were tested for HLA class I and II antibodies as well as granulocyte antibodies, if HLA antibodies were not identified. RESULTS: HLA class II antibodies were identified, in at least one donor, in 7 (64%) of 11 cases of TRALI. HLA class I antibodies were identified in combination with HLA class II antibodies in 5 of these 7 cases. HLA class I antibodies were exclusively identified in 2 cases. Granulocyte antibodies were identified in 1 case, and no antibodies were identified in another. CONCLUSION: In addition to HLA class I antibodies, HLA class II antibodies are associated with TRALI. Testing of donors for HLA class II antibodies as well as HLA class I and granulocyte antibodies is recommended as part of the investigation of suspected cases of TRALI.     

急性肺损伤环氧合酶2表达的研究

目的：探讨急性肺损伤（ＡＬＩ）肺组织环氧合酶 ２（ＣＯＸ ２）ｍ ＲＮＡ 表达和ＡＬＩ中前列腺素（ＰＧｓ）变化的关系,以及ＣＯＸ ２ 在ＡＬＩ发病中的可能作用。方法：在脂多糖（ＬＰＳ）诱发的ＡＬＩ模型,采用逆转录聚合酶链反应,检测肺组织ＣＯＸ ２ ｍ ＲＮＡ表达情况,并观察了ＰＧｓ的变化。结果：生理盐水对照组的大鼠肺组织有极少量的ＣＯＸ ２ ｍ ＲＮＡ表达（０．３２±０．１１）;而在ＡＬＩ大鼠,肺组织ＣＯＸ ２ｍ ＲＮＡ表达显著增加,比生理盐水对照组升高达５～８ 倍,同时伴有ＰＧｓ的升高〔生理盐水对照组为（１４１．６４±４１．７９）μｇ·Ｌ－ １ ·ｇ－ １ ,ＡＬＩ大鼠分别为（１９０．５３±４７．９１）～（４７０．９５±１８４．１７）μｇ·Ｌ－ １·ｇ－ １ 〕。结论：正常肺组织有极少量的ＣＯＸ ２ ｍ ＲＮＡ表达,ＣＯＸ ２参与ＡＬＩ的发病,并可能是引起ＡＬＩ时ＰＧｓ升高的主要同工酶。     

白细胞介素-10对内毒素诱导急性肺损伤大鼠炎症因子的影响

目的研究白细胞介素-10(IL-10)对内毒素诱导急性肺损伤(ALI)大鼠肺组织炎症因子mRNA表达的影响,探讨IL-10对急性肺损伤的保护作用。方法24只SD大鼠随机分为3组:对照组,实验组,治疗组。实验组于尾静脉注射内毒素,治疗组注射内毒素和IL10,对照组注射生理盐水。测定各组肺组织肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)和白介素-6(IL-6)mRNA表达和血浆TNF-α、IL-1β和IL-6水平,观察各组大鼠肺组织的病理改变。结果TNF-α、IL-1β和IL6mRNA的表达:实验组、治疗组高于对照组,P<0.01;实验组高于治疗组,P<0.05。血浆TNF-α、IL1-β、IL-6:实验组高于治疗组对照组,P<0.05。肺组织病理改变:治疗组明显轻于实验组。结论IL10能抑制内毒素诱导ALI大鼠肺组织中TNF-α、IL-1β和IL6mRNA的表达,降低血浆炎症因子水平,减轻肺组织的病理损害,能起到治疗ALI的作用。     

颈脊髓切断对内毒素血症大鼠急性肺损伤的影响

目的 研究颈脊髓切断对内毒素血症大鼠急性肺损伤的影响及可能机制.方法 72只SD大鼠随机分为3组:正常对照组(NC组,8只),内毒素血症组(ET组,32只)及内毒素血症+颈脊髓切断组(TCSC组,32只),后两组按不同时间点(3、6、12和48 h)又分为4个亚组,每个亚组8只.静脉注射脂多糖(LPS)10 mg/kg制备内毒素血症模型.TCSC组注射LPS前切断大鼠颈7脊髓.在不同时间点采血,并留取肺组织.采用高效液相色谱仪-电化学检测法和酶联免疫吸附法(ELISA)分别测定血浆去甲肾上腺素(NE)和白细胞介素-6(IL-6)的浓度;用血气分析仪检测动脉血氧分压(PaO2);观察各组大鼠肺组织病理学改变及肺湿/干重(W/D)比值.结果 TCSC组6、12和48 h血浆NE浓度、肺W/D比值较ET组均显著降低,PaO2较ET组显著升高,差异均有统计学意义(P均<0.05);TCSC组肺损伤程度减轻;3、6、12和48 h血浆IL-6均明显低于ET组(P均<0.05).相关性分析显示,血浆NE与IL-6浓度呈显著正相关(r=0.458,P<0.05),与PaO2呈显著负相关(r=0.528,P<0.05).结论 切断大鼠颈脊髓后造成去交感神经支配可能通过抑制肾上腺素能受体的过度激活而减轻内毒素血症大鼠急性肺损伤的程度,继而改善肺的氧合.     

Effect of interleukin-10 (IL-10) on experimental LPS-induced acute lung injury

The purpose of this study was to clarify the role of interleukin-10 (IL-10) during the development of acute lung injury induced by lipopolysaccharide (LPS) in a mouse model. When LPS was given to nude mice, the mortality rate was 100% at 48 h of the observation period. However, mortality was reduced to 30% when IL-10 was added concomitantly (P < 0.01). In the IL-10 group, a significant reduction of inflammatory change in lung tissue was observed. It was also found that peripheral neutrophils increased when IL-10 was added. When LPS and IL-10 were given concomitantly, the level of tumor necrosis factor (TNF)-α in both serum and bronchoalveolar lavage fluid (BALF) decreased significantly (P < 0.05). In-vitro observations were made concerning the influence of human neutrophils. Both neutrophil superoxide (O₂ ⁻) and elas-tase production were increased by TNF-α stimulation, while significant inhibition was seen with the concomitant dosing of IL-10 (P < 0.05). TNF-α stimulation increased the occurrence of adhesion molecules for neutrophil surface, lymphocyte function-associated antigen-1 (LFA-1), and macrophage antigen-1 (Mac-1). LPS stimulation greatly increased the occurrence of neutrophil surface 55-kDa TNF-receptor [TNF-R (p55)], when observation was made under laser microscopy. However, no significant occurrence was seen with IL-10 concomitant dosing. The above results suggested that IL-10 inhibited TNF-α production and neutrophil activity in LPS-induced acute lung injury, which led to a reduction of the lung tissue injury. Received: February 18, 1999 / Accepted: December 20, 1999     

Impact of a transfusion-related acute lung injury reduction strategy on apheresis platelet collections

Background: Most blood centers in the US have implemented transfusion‐related acute lung injury (TRALI) mitigation strategies for apheresis platelet (AP) donations based on theoretical impact of donor loss. The aim of this study is to determine the actual impact of a TRALI mitigation strategy in a US blood center. Study Design and Methods: Daily collection events and resulting products were retrospectively obtained before and after implementation of a TRALI reduction strategy (HLA antibody testing female AP donors four or more pregnancies) for comparison. The retention rate of reassigned donors was determined by reviewing whole blood (WB) and/or apheresis red blood cell (AR) donations post reassignment. Data were obtained to compare donor frequency and split rate from reassigned (historical data) and new AP donors. Results: Mean daily collections (27.7 vs. 30.0) and total products (12,211 vs. 12,957) were significantly higher after implementation, but the number of products/collection event was lower (1.49 vs. 1.40). Mean collections/donor/year (4.0 vs. 1.8) and split rate (36% vs. 27%) were historically higher for reassigned (n = 45) versus new AP donors (n = 1,090). Seventy‐three of 112 donors (65%) testing positive for HLA antibodies returned for WB or AR donations, 31 of 45 (69%) active AP donors returned. Conclusions: Donor loss may not be adequate to estimate impact on AP inventory, as donation characteristics may differ between new donors and those reassigned. We show successful implementation of a TRALI mitigation strategy by increasing collection goals and AP donor recruitment efforts beyond donor loss. Retaining the majority of reassigned donors is feasible. J. Clin. Apheresis 2012. © 2012 Wiley Periodicals, Inc.     

白细胞介素-10对急性肺损伤炎症/抗炎介质表达的影响

目的探讨白细胞介素-10(IL—10)对急性肺损伤(ALI)大鼠炎症介质／抗炎介质表达的影响。方法向气道内滴注内毒素(LPS，10mg／kg)建立大鼠ALI模型。54只雄性SD大鼠随机分为对照组、LPS损伤组、LPS加IL-10组，每组18只，各组又分为2、6和24h3个亚组，每个亚组各6只。按各时间点观察大鼠动脉血氧分压(PaO2)、支气管肺泡灌洗液(BALF)中细胞总数及分类计数、肺系数、BALF总蛋白水平及肺病理，同时用逆转录-聚合酶链反应(RT—PCR)方法检测肺组织中炎症介质／抗炎介质的表达。结果①LPS损伤组大鼠PaO2呈进行性降低；肺系数、BALF总蛋白水平及BALF中细胞总数均明显增加，分类以中性粒细胞为主；肺病理示肺内中性粒细胞大量浸润，伴出血、透明膜形成。LPS加IL-10组的各项指标均较LPS损伤组减轻。②LPS损伤组肺组织肿瘤坏死因子-α(TNF—α)mRNA表达于2h达高峰，随后迅速下降；白细胞介素-1β(IL—1β)mRNA表达于2h显著升高，6h达高峰，随后迅速下降；IL-1受体拮抗剂(IL—1ra)mRNA表达6h开始升高，且为峰值。24h仍高于对照组。LPS加IL-10组肺组织TNF—αmRNA、IL-1βmRNA表达受抑，而IL—1ra mRNA表达不受影响。结论①ALI早期TNF—αmRNA、IL-1βmRNA表达明显增加，而IL—1ra mRNA表达滞后，提示在无外来干预情况下，ALI早期存在炎症介质／抗炎介质的失衡。②IL-10可明显抑制炎症介质表达，不影响抗炎介质表达，有利于重建炎症介质／抗炎介质平衡，减轻LPS所致ALI。