中性粒细胞在大鼠急性重症胰腺炎肺损伤中的作用机制

目的:探讨急性重症胰腺炎(ASP)合并急性肺损伤时肺泡灌洗液中性粒细胞(PMN)凋亡和坏死的发生规律及可能涉及的作用机制.方法:选取雄性SD大鼠48只,分为ASP实验组(24只)、对照组(24只).实验组大鼠穿刺胰胆管并注入35g/L牛磺胆酸钠制作ASP大鼠模型,分别在制模后3,6,12 h剖杀,于预定时相取支气管灌洗液,密度梯度离心分离PMN,用流式细胞仪测定PMN凋亡、坏死比例,同时测定乳酸脱氢酶(LDH)含量、肺通透指数.结果:ASP组大鼠肺灌洗液中PMN存活细胞比例增加(P＜0.01),凋亡延迟.同时,肺灌洗液LDH明显升高(P＜0.01),肺通透指数显著增加(P＜0.01).结论:ASP合并急性肺损伤时,PMN凋亡延迟,造成PMN持续处于激活状态及毒性内容物的持续释放,与急性肺损伤密切相关.     

大鼠内毒素血症时外周血及肺泡内PMN死亡方式及呼吸爆发的检测

目的 观察大鼠内毒素血症时肺组织中及外周血中性粒细胞（PMN）凋亡,坏死及功能改变的差异。方法 Wistar大鼠25只,腹腔注射内毒素（LPS）（O55：R5,5mg/kg)造成内毒素血症,分别在给予LPS前（对照）及给予LPS后2、4、8、12h（每组5只动物）取血及支气管肺泡灌洗,密度梯度法分离PMN,用流式细胞仪测定凋亡和坏死比例以及呼吸爆发功能的改变。结果 内毒素血症时,外周血和支气管肺泡灌洗液中PMN凋亡细胞比例相似,但与对照相比,外周血PMN坏死比例明显增加,呼吸爆发能力明显受抑,而支气管肺泡灌洗液PMN坏死比例显著减少,呼吸爆发能力显著增强。结论 在内毒素血症时,扣押于肺组织中的PMN在凋亡和坏死上表现出与外周血PMN不同的改变,其结果是组织中PMN存活PMN增加,并持续处于活化状态,这与PMN造成组织损伤有关。     

急性肺损伤大鼠模型评价

目的：建立脂多糖（LPS）和海水淹溺（SW）两种诱因所致急性肺损伤大鼠模型,在造模后不同时间点观察肺组织的病理改变,检测血清及支气管肺泡灌洗液中炎症因子浓度、支气管肺泡灌洗液中总蛋白浓度以及肺组织湿重/干重比。方法：将28只健康雄性SD大鼠随机分为空白对照组（Control组）4只、脂多糖组（LPS组）12只和海水淹溺组（SW组）12只,大鼠气管内分别注入LPS溶液和海水建立急性肺损伤模型。造模后6 h、12 h、24 h LPS组和SW组各取4只大鼠,麻醉后取静脉血、支气管肺泡灌洗液（BALF）及肺组织,Control组4只大鼠一次性进行相同实验。采用ELISA法测定血清及BALF中IL-1、IL-6、TNF-α浓度,BALF中总蛋白含量。取左肺下叶计算肺湿重/干重比,左肺上叶行病理切片HE染色,观察肺组织病理学改变。结果：造模后24 h内LPS及SW组大鼠肺组织均出现中性粒细胞聚集及肺损伤病理学改变。造模后6 h、12 h、24 h LPS组和SW组血清IL-1浓度高于Control组,造模后6 h LPS组血清IL-6及TNF-α浓度高于Control组,SW组IL-6浓度高于C...     

TNF-α、IL-8与急性重症胰腺炎肺损伤中PMNs凋亡延迟的相关性研究

目的探讨肿瘤坏死因子-α(TNF-α)和白细胞介素-8(IL-8)在急性重症胰腺炎(acute severe pancreatitis,ASP)合并急性肺损伤中中性粒细胞(polymorphonuclear leukocyte,PMNs)凋亡延迟的相关性及其机制。方法选取雄性SD大鼠48只,穿刺胆胰管并注入3.5%牛磺胆酸钠制作ASP合并急性肺损伤大鼠模型,分为牛磺胆酸钠注射后3、6、12 h及对照组。病理检测胰腺及肺组织;于预定时相取支气管灌洗液,密度梯度离心分离PMNs,流式细胞仪测定PMNs凋亡、坏死比例;ELISA检测灌洗液中TNF-α及IL-8的含量;检测NF-κB在肺组织中的表达。结果 ALI大鼠肺灌洗液中PMNs凋亡、坏死比例增加,凋亡延迟。支气管-肺泡灌洗液中的TNF-α及IL-8的含量较对照组显著增加,灌洗液中细胞TNF-α及IL-8 mRNA表达增加,不同干预时间组间具有显著差异,具有时间依赖效应;肺组织中NF-κB的表达显著增加。结论TNF-α、IL-8在ASP合并急性肺损伤中可能发挥一定的作用。     

抑制补体对内毒素致急性肺损伤的保护作用

目的 探讨抑制补体对内毒素致急性肺损伤的保护作用.方法 采用眼镜蛇毒因子(CVF)去除补体.以脂多糖(LPS)造成大鼠急性肺损伤.将40只健康雄性SD大鼠随机分为LPS损伤组、3个不同时间CVF组和生理盐水对照组.通过大鼠尾静脉注射5 mg/kg LPS,造成急性肺损伤模型.CVF组于注射LPS 前24 h,通过尾静脉注射50 u/kg CVF去除补体.在给予LPS后分别于0.5、2、4 h采集标本.分别测定各组血清补体活性和蛋白含量、肺泡灌洗液(BALF)中蛋白、TNF-α、IL-8、ICAM-1含量及多形核白细胞(PMN)比、计算肺通透指数(LPI )、测定肺湿/干质量比、检查肺组织病理学变化情况等.结果 LPS组肺间质水肿、出血,大量炎性细胞浸润,而CVF组肺组织损伤明显轻于LPS组; CVF组肺湿/干质量比、LPI、PMN比均明显低于LPS组(P<0.05),与对照组比较差异无统计学意义.而CVF各组BALF 中TNF-α、IL-8、ICAM-1浓度均低于LPS组,但差异无统计学意义.结论 补体在内毒素致急性肺损伤早期具有重要作用,抑制补体可以有效减轻肺组织损伤,减少肺组织液渗出和中性粒细胞聚集.     

沙奎那韦对脂多糖诱导急性肺损伤大鼠PI3K-AKt-NF-κB信号通路的影响

目的：研究沙奎那韦（SQV）对脂多糖（LPS）诱导急性肺损伤（ALI）大鼠的保护作用及其对PI3K-AKt-NF-κB信号通路的影响。方法：将36只雄性SD大鼠随机分为对照组（Control组）、LPS模型组（LPS组）、SQV处理的LPS模型组（LPS+SQV组）,每组12只。LPS+SQV组大鼠在LPS造模前予以200 mg/kg·d-1的SQV连续5 d灌胃处理,Control组与LPS组大鼠用等体积的生理盐水灌胃处理,第5天LPS组和LPS+SQV组大鼠采用腹腔注射5 mg/kg的LPS制备ALI模型,造模12 h后腹腔注射120mg/kg戊巴比妥处死大鼠;苏木精—伊红（HE）染色观察各组肺组织病理变化,计算各组大鼠肺组织湿/干（W/D）比值,TUNEL染色对肺组织细胞凋亡水平进行测定,采用ELISA法检测每组大鼠支气管肺泡灌洗液中炎症因子：肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、白细胞介素-10(IL-10)的表达量,Western blotting检测肺组织中PI3K-AKt-NF-κB信号通路相关蛋白IκBa的表达水平和...     

不同CO浓度对ALI大鼠肺炎性变化的影响

目的探讨减轻ALI（急性肺损伤）大鼠肺炎性改变的最佳一氧化碳浓度。方法随机将30只条件相当的大鼠分为五组：正常对照组，LPS（大肠杆菌内毒素）组，LPS＋3％CO组，LPS＋8％CO组，LPS＋15％CO组。24h测动脉血和支气管肺泡灌洗液（BAIF）中细胞因子IL-8、TNF含量。并取五组大鼠肺组织，做病理切片进行比较。结果LPS组，在静脉注射LPS后24h其动脉血和BALF中细胞因子IL-8、TNF含量明显增加，显著高于正常对照组；LPS＋3％CO组细胞因子IL-8、TNF含量虽有增高，但与正常对照组之间无明显差异；LPS＋8％CO组，LPS＋15％CO组与LPS组无明显差异；病理切片的比较亦提示LPS＋3％（20组其炎性改变最轻。结论给大鼠静脉注射LPS造成ALI的同时给予低浓度（3％）CO气体吸入，可降低细胞因子水平从而减轻急性肺损伤的炎性反应。     

丙氨酰谷氨酰胺对脓毒症大鼠肺损伤的保护作用

目的：探讨丙氨酰谷氨酰胺对脓毒症大鼠急性肺损伤的保护作用及其机制。方法：静脉注射内毒素（LPS）3mL（6mg／kg）复制大鼠脓毒症急性肺损伤模型,40只健康Wistar大鼠,分为4组,即对照组（静脉注射等量生理盐水28mL／kg）、内毒素组[先后静脉注射生理盐水25mL／kg和内毒素3mL／kg（6mg／kg）]、丙氨酰谷氨酰胺治疗组[先后静脉注射4．5％力太（丙氨酰谷氨酰胺注射液）25mL/kg和内毒素3mL／kg（6mg／kg）]、谷氨酰胺治疗组[先后静脉注射3％谷氨酰胺25mL／kg和内毒素3mL／kg（6mg／kg）]。在静脉注射前（T0）,注射后6h（T1）,各抽血1mL。注射6h后,处死大鼠,用EusA法测定各时点血清TNF-α,IL-1β,IL-8的浓度,测定肺组织湿／干重比、支气管肺泡灌洗液的总蛋白浓度,光学显微镜下观察肺组织病理改变,原位TUNEL技术进行肺组织细胞凋亡检测分析。结果：与LPs组比较,丙氨酰谷氨酰胺治疗组、谷氨酰胺治疗组的肺组织湿／干重比、支气管肺泡灌洗液的总蛋白浓度,血清TNF-α,IL-1β,IL-8浓度明显降低（P＜0．05）;丙氨酰谷氨酰胺治疗组、谷氨酰胺治疗组的肺组织损伤程度明显减轻而且凋亡指数也较LPS组显著降低（P＜0．05）。结论：静脉给予丙氨酰谷氨酰胺对脓毒症大鼠急性肺损伤有保护作用。     

肺泡灌洗液计数中性粒细胞百分比与血浆MMP-9、 TIMP-1在油酸制备急性肺损伤大鼠模型中的相关性研究

目的检测油酸制备大鼠急性肺损伤模型支气管肺泡灌洗液（bronchoalveolarlavagefluid,BALF）计数中性粒细胞（polymorphonucearleukocyte,PMN）百分比及血浆基质金属蛋白酶9（matrixmetalloproteinases9,MMP-9）、组织基质金属蛋白酶抑制因子-1（tissuematrixmetalloproteinaseinhibitor-1,TIMP-1）含量,分析BALF中性粒细胞百分比与MMP-9及TIMP-1的相关性及临床意义。方法雄性SD大鼠36只随机分为3组：空白对照组（n=12）、油酸造模2h组（n=12）、油酸造模6h组（n=12）。空白对照组大鼠尾静脉注射生理盐水（0．1ml／kg）6h后观察。油酸造模组大鼠尾静脉缓慢注射油酸（OA,0．1ml／kg）2、6h后观察,以复制油酸诱导大鼠急性肺损伤模型。观察及检测指标为光镜下肺组织病理形态学变化、动脉血氧分压（PaO,）、肺湿／干重比（W／D）、血浆MMP-9和TIMP-1含量及肺泡灌洗液中性粒细胞计数百分比。结果光镜下,与空白对照组比较,油酸造模组大鼠肺组织可见明显形态学改变。2h及6h油酸造模组PMN％明显升高,PaO,明显降低,IQA及W／D明显升高,（P均〈0．01）;血浆MMP-9含量明显升高（P〈0．001）,血浆TIMP-1含量明显降低（P〈0．05）血浆MMP-9含量与PMN％均呈高度正相关,血浆TIMP-1含量与PMN％均呈高度负相关。结论油酸制备急性肺损伤大鼠模型肺泡灌洗液PMN％明显升高,血浆MMP-9含量明显升高,TIMP-1含量明显降低。血浆MMP-9、TIMP—l与肺泡灌洗液PMN％呈高度相关性;检测血浆MMP-9、TIMP-1有助于急性肺损伤的病理诊断和治疗,从而为临床急性肺损伤的诊断、治疗及预后提供更为简单、可行、准确的检测方法和途径。     

氢气对百草枯中毒大鼠急性肺损伤的保护作用

目的:探讨氢气对百草枯中毒大鼠急性肺损伤的保护作用。方法:24只大鼠随机分为3组:对照组、百草枯组和氢气组,百草枯组和氢气组腹腔注射百草枯(35mg/kg),氢气组于注射后立即开始吸入含2%氢气的空气。72h后检测肺湿/干比、肺泡灌洗液PMN、PaO2、肺损伤评分、肺组织丙二醛含量。结果:与对照组比较,百草枯组、氢气组肺湿/干比、肺泡灌洗液PMN、肺损伤评分、肺组织丙二醛含量升高,PaO2降低;与百草枯组比较,氢气组肺湿/干比、肺泡灌洗液PMN、肺损伤评分、肺组织丙二醛含量降低,PaO2升高。结论:吸入氢气能够通过抑制脂质过氧化,抑制白细胞在肺部的聚集,从而减轻百草枯中毒后引起的急性肺损伤。     

地塞米松对脂多糖致大鼠急性肺损伤的治疗作用

目的:探讨急性肺损伤(Acate lung injury,ALI)发生早期给予地塞米松的治疗作用.方法:大鼠尾静脉注射5mg/kg脂多糖(Lipopolysacharide,LPS),造成ALI模型.于注射LPS 1 h后,腹腔注射地塞米松(10 mg/kg),1 h后采集标本,分别测定血清蛋白含量、肺泡灌洗液(Broncho alveolar lavage fluid,BALF)中蛋白、TNF-α、IL-8、ICAM-1的含量,计算肺通透指数(Lung alveolar permeability index,LPI)、肺湿/干重比,检查肺组织病理学变化情况.实验平行设置生理盐水对照组和LPS损伤组.结果:肺组织病理切片检查表明,LPS组肺间质水肿、出血,大量炎性细胞浸润,而地塞米松组肺组织损伤显著轻于LPS组.地塞米松组肺湿/干重比、BALF中PMN比、LPI均显著低于LPS组(P<0.05),与正常对照组相比没有显著差异.LPS组BALF中TNF-α、IL-8、ICAM-1浓度高于正常对照组(P<0.05),而地塞米松组与对照组相比,差异无统计学意义(P>0.05 ).结论:在ALI发生早期给予大剂量地塞米松,可以减轻肺组织损伤,减少肺组织液渗出和中性粒细胞聚集.     

维生素E对LPS诱导的急性肺损伤中氧化应激的影响

目的:探讨维生素E对脂多糖(lipopolysaccharide,LPS)诱导的急性肺损伤(acute lung injury,ALI)中氧化应激状态的影响。方法:以Wistar大鼠为研究对象,实验分成正常对照组、ALI组及维生素E预处理组。用LPS作用于大鼠6 h后检测各组大鼠肺组织中丙二醛(Malondialdehyde,MDA)的含量、乳酸脱氢酶(lactate dehydrogenase,LDH)及超氧化物歧化酶(superoxide dismutase,SOD)活性,并应用RT-PCR及ELISA法检测大鼠肺组织中TNF-α的水平。结果:ALI组与正常对照组比较SOD活性下降、LDH的活性增强、MDA的含量升高,且TNF-αmRNA及蛋白的表达增加(P﹤0.05);维生素E预处理组与ALI组比较SOD活性增强,LDH的活性减弱,MDA的含量降低,TNF-αmRNA及蛋白的表达降低(P﹤0.05)。结论:维生素E预处理可减轻LPS诱导的ALI大鼠肺组织的脂质过氧化损伤,减少炎症因子的表达,发挥一定的抗损伤效应。     

PMN apoptosis and its relationship with the lung injury after chest impact trauma

Background Polymorphonuclear neutrophil (PMN), one of the most important inflammatory cells, functions throughout the initiation, progression and resolution of inflammation. This study aimed at investigating the relationship between PMN apoptosis and the lung injury after chest impact trauma. Methods PMNs were purified from rabbits subjected to the chest impact trauma and their apoptosis, necrosis, survival and respiratory burst were detected by flow cytometry. Meanwhile, lactate dehydrogenase and (LDH) ［Ca2+］i were measured. Results The delayed apoptosis of PMNs in bronchoalveolar lavage fluid was observed from 2 hours to 12 hours after trauma, and viable cells increased. Respiratory burst of PMNs in bronchoalveolar lavage fluid was increased significantly from 2 hours with the peak at 8 hours. Meanwhile, lactate dehydrogenase in bronchoalveolar lavage fluid was higher than that in control (P&lt;0.05) from 4 hours to 24 hours, and intracellular free Ca2+ in PMN was increased temporarilly. Conclusions Retention of PMN in tissues and the abnormality in apoptotic pathway inevitably generate persistent activation of PMN and excessive release of toxic substances, resulting in tissue injury. The temporary increase of intracellular free Ca2+ may be responsible for the delayed apoptosis of PMN.     

桃叶珊瑚苷减轻脂多糖诱导的小鼠急性肺损伤

目的：探讨预防性给予桃叶珊瑚苷(aucubin,AU)对脂多糖(lipopolysaccharide,LPS)诱导的小鼠急性肺损伤 (acute lung injury,ALI)的作用。方法：以成年雄性BABL/c小鼠为研究对象,随机分为对照组、ALI组和AU处理组,每 组16只。气管注射LPS(5 mg/kg)复制ALI小鼠模型,AU处理组于造模前30 min腹腔注射AU(10 mg/kg)。LPS注射6 h后处 死小鼠,采用HE染色检测肺组织形态学改变,并进行损伤评分;采用real-time PCR法检测小鼠肺组织炎症因子肿瘤坏 死因子-α(tumor necrosis factor-α,TNF-α)和白细胞介素10(interleukin 10,IL-10)的mRNA表达;收集小鼠支气管肺泡灌洗 液(bronchoalveolar lavage fl uid,BALF)进行细胞计数、检测BALF中的总蛋白量、乳酸脱氢酶(lactic dehydrogenase,LDH) 活性以及TNF-α和IL-10的蛋白含量。结果：与ALI组小鼠相比,AU处理组小鼠肺组织病理损伤明显减轻、损伤评分降 低,BALF总细胞、中性粒细胞和巨噬细胞数目显著减少,LDH活性和总蛋白含量亦明显降低(均P<0.01)。同时,AU 可减少ALI小鼠肺内TNF-α mRNA和蛋白的表达,增加IL-10 mRNA和蛋白的表达(均P<0.01)。结论：AU可减轻LPS诱导 的小鼠ALI。     

Pro-apoptotic role of NF-κB pathway inhibition in lipopolysaccharide stimulated polymorphonuclear neutrophils

Objective To investigate the role of nuclear factor kappa B (NF-κB) pathway inhibition in lipopolysaccharide (LPS)-stimulated apoptosis of polymorphonuclear neutrophils (PMNs).Methods Rats with acute lung injury induced by LPS intratracheal instillation and cultured human venous PMNs were studied. Pyrrolidine dithiocarbamate (PDTC) and gliotoxin were used as NF-κB inhibitors. Additionally, to explore the role of extracellularly regulated protein kinase as an upstream signal in NF-κB pathway on regulating LPS-stimulated PMN apoptosis, PD098059, the specific inhibitor of extracellularly regulated protein kinase, was also applied. The lung injury was determined by protein content and PMN numbers in bronchoalveolar lavage fluid. PMN apoptosis was measured by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) end labeling and DNA fragmentation. IκBα degradation was analyzed by Western blot. NF-κB DNA binding activity was detected by an electrophoretic mobility shift assay.Results (1) The increase of protein content and PMN numbers in bronchoalveolar lavage fluid induced by LPS (100μg per rat) intratracheal instillation were alleviated by PDTC (50, 100, or 200mg/kg, i. p. ) in a dose-dependent manner. (2) PMNs apoptosis in vivo or in vitro was delayed by LPS, and accelerated by PDTC, gliotoxin or PD098059 pretreatment. (3) IκBα degradation and increased NF-KB DNA binding activity mediated by LPS were inhibited by PDTC, gliotoxin or PD098059 pretreatment.Conclusion Inhibition of either NF-κB itself or the upstream signals in NF-κB pathway such as extracellularly regulated protein kinases has therapeutic effect on LPS-induced acute lung injury, in which the dysregulation of PMN apoptosis plays an important role.     

内毒素诱导的肝细胞及枯否细胞凋亡与肝脏损伤的关系

目的探讨内毒素、肿瘤坏死因子（ＴＮＦ）在诱导枯否细胞及肝细胞凋亡过程中的作用及其与肝脏损伤的关系。方法采用细胞死亡ＥＬＩＳＡ法分别检测枯否细胞,以及和肝脏细胞联合培养时,对不同浓度的内毒素,在不同时相点两种细胞的凋零密度,同时观察培养上清中丙氨酸转氨酶（ＡＬＴ）,乳酸脱氢酶（ＬＤＨ）含量变化。结果枯否细胞的凋亡数量随着培养时间的延长（３～２４小时）和内毒素浓度的增加（０～１０μｇ／ｍｌ）明显增加。而枯否细胞与肝细胞联合培养时,在内毒素浓度大于１μｇ／ｍｌ时,细胞凋亡数显著上升。ＴＮＦ单克隆抗体可阻断内毒素诱导的枯否细胞及肝细胞凋亡。ＬＤＨ及ＡＬＴ含量在内毒素浓度高于１μｇ／ｍｌ,且培养６小时后,有明显升高,晚于凋亡出现。结论ＴＮＦ介导了内毒素所致的枯否细胞及肝细胞的凋零。而且细胞凋亡早于细胞损伤的出现。大量凋零细胞的出现,使枯否细胞对内毒素的灭活作用降低进而可能导致肝细胞的凋零及损伤。     

血红素加氧酶-1重组乳酸乳球菌灌胃对内毒素诱导大鼠急性肺损伤的作用

目的:利用基因工程原理合成携带血红素加氧酶-1(HO-1)基因的乳酸乳球菌,给正常大鼠灌胃后,观察其对内毒素诱导大鼠急性肺损伤的保护效应。方法:随机将30只健康清洁级SD大鼠分为对照组(LPS组,n=10)、携带HO-1的乳酸乳球菌灌胃组(HO组,n=10,LPS模型建立前24 h灌胃)、拮抗剂组[锌原卟啉(ZnPP)组,n=10,HO灌胃24 h后,LPS模型建立前1 h腹腔注射ZnPP 10μmol/kg];LPS模型建立后4 h取材,比较各组动物支气管灌洗液(BALF)中髓过氧化物酶(MPO)活性、中性粒细胞(PMN)计数、肺组织湿干重比(W/D)、肺组织MPO活性,并在光镜下观察肺组织病理学改变。结果:与LPS组比较,HO组BALF中MPO、PMN计数和肺组织W/D均降低(P<0.05),肺组织病理学损伤减轻;与HO组比较,ZnPP组BALF中MPO、PMN计数和肺组织W/D均升高(P<0.05),肺组织病理学损伤加重;ZnPP组与LPS组比较差异无统计学意义(P>0.05)。结论:预先给大鼠用携带HO-1基因的乳酸乳球菌灌胃,可对内毒素诱导急性肺损伤大鼠产生一定的保护作用。     

Role of tumor necrosis factor-alpha and interleukin-1beta on lung dysfunction following hemorrhagic shock in rats.

BACKGROUND: Hemorrhagic shock occasionally causes a fatal outcome following an outbreak of lung dysfunction, but the precise mechanism has not been clearly elucidated. Several studies have indicated that hemorrhagic shock causes a delayed vascular inflammatory decompensation and leads to inflammation-related organ dysfunction. Tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta are known as major proinflammatory cytokines that play an important role in excessive autolytic inflammation, finally inducing organ dysfunctions. In this study, the role of TNF-alpha and IL-1beta on lung dysfunction following hemorrhagic shock was examined by using FR167653, a potent inhibitor of TNF-alpha and IL-1beta production that acts by suppressing p38 mitogen-activated protein kinase (MAPK). MATERIAL/METHODS: Hemorrhagic shock was induced in anesthetized male rats by bleeding via a common carotid catheter for 20 minutes to 25% of total body blood volume without fluid resuscitation. Mean blood pressure, heart rate and arterial blood gas components were recorded up to 5 hours after the bleeding. The levels of TNF-alpha, IL-1beta and lactic dehydrogenase (LDH)-3 isozyme were measured in the serum of pulmonary venous blood. The lung tissue was excised for the assay of mRNA and for histopathological study. RESULTS: The expressions of mRNA for TNF-alpha and IL-1beta in the lung tissue and the concentrations of both cytokines in pulmonary serum increased after a hemorrhage. Inflammation-related injuries and function deterioration were observed in the lung following hemorrhagic shock. These hemorrhagic changes were inhibited by pretreatment with FR167653. CONCLUSIONS: TNF-alpha and IL-1beta play a key role in the development of inflammation-related lung dysfunction following hemorrhagic shock. Our model should be useful to explain the pathogenesis of lung dysfunction following hemorrhagic shock.     

乌司他丁在体外循环中肺保护机制的研究

目的探讨体外循环（cardiopulmonary bypass,CPB）所引起的肺组织炎性损伤,研究术中应用乌司他丁（UTI）对肺的保护作用及可能的机制。方法25例患者随机分为两组,实验组于转流后将UTI加入体外循环机中。动态检测两组患者左、右房中性粒细胞数（polymorphonuclear neutrophils,PMN）、血小板数（Plt）;血清白细胞介素-6（IL-6）、白细胞介素-10（IL-10）、肿瘤坏死因子-α（TNF-α）水平;肺顺应性;CPB后肺组织电镜检查变化结果。结果①对照组心脏复跳后左房PMN、Pt明显低于右房（P〈0．05）;②CPB开始后,两组桡动脉血IL-6、TNF-α进行性升高,心脏复跳后逐渐下降,对照组增高更显著（P〈0．05）。③CPB开始后,两组桡动脉血IL-10进行性增高,心脏复跳后逐渐下降,实验组增高更显著（P〈0．05）。④肺顺应性在停CPB后均降低,对照组降低更显著,与实验组比较有显著差异（P〈0．05）。⑤电镜观测：实验组Ⅰ型、Ⅱ型肺泡细胞内细胞器、细胞形态学的改变较轻。结论UTI能减轻CPB后肺损伤,保护术后肺功能。