白细胞介素10基因转染抑制机械通气肺损伤的实验研究
详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文
摘要
目的:机械通气(mechanical ventilation MV)已广泛应用于手术麻醉、危重病医学、急诊医学、内科学等多个临床领域,但使用呼吸机本身所引起的机械通气肺损伤(ventilator-induced lung injury,VILI),亦成为影响危重病患者预后的重要因素之一。本实验采用分子生物学技术,将IL-10基因转染到肺组织以抑制VILI细胞因子、炎性介质的释放,并通过观察TNF-α、IL-1β、IL-8、IL-10及肺组织形态学的变化对该治疗方法进行评价,为临床防治机械通气肺损伤提供了新的实验性理论依据。
     方法:将54只SD雄性健康大鼠随机分为9组,每组6只。A组为空白对照组;L组为低压力组(气道压力设为15cmH_2O),根据通气时间分为2小时组(L_2)和4小时组(L_4);H组为高压力组(气道压力设为25cmH_2O),根据通气时间分为2小时组(H_2)和4小时组(H_4);B组为空白病毒转染组(气道压力设为25cmH_2O),根据通气时间分为2小时组(B_2)和4小时组(B_4);T组为IL-10基因转染组(气道压力设为25cmH_2O),根据通气时间分为2小时组(T_2)和4小时组(T_4)。处理组大鼠以10%的水合氯醛0.3g/kg行腹腔注射麻醉,于颈部正中切口行气管插管,机械通气的条件下于胸骨左缘3、4肋间开胸,于右心室注射进行转染,其中L与H组为乳酸钠林格液,B组为空白病毒,T组为含白介素10的腺病毒(剂量均为0.1ml)。关胸后每日肌肉注射青霉素10万单位预防感染。转染48小时后,重新切开气管并插管进行持续机械通气,通气过程中根据体动酌情追加麻醉药。达到预定通气时间后,于腹主动脉采血5ml,以3000r/min的速度离心15分钟,取上清液保存于-80℃冰箱待检测;取肺组织,分别做电镜和光镜的检查。集中检测TNF-α、IL-1β、IL-8、IL-10。实验结果均以均数±标准差((?)±s)表示,各组间比较采用独立样本t检验,组内比较采用配对t检验,应用SPSS11.5统计分析软件对实验数据进行统计学处理,P<0.05为有统计学意义。
     结果:(1)HE染色结果显示:光镜下A组肺泡结构未见异常,L组肺泡腔内略有渗出、血管周围有少量炎症细胞,随通气时间延长病变加重;H、B组上述病理改变加重;T组病理变化较B组为轻;(2)电镜结果显示:A组肺组织中Ⅰ型细胞、Ⅱ型细胞及内皮细胞结构完整,无明显异常;L、H、B、T组均可见不同程度的线粒体肿胀、脱落、嵴消失,内质网扩张,细胞核变大,细胞核与细胞质间隙增宽,染色质分布不均匀,板层小体肿胀,微绒毛减少;L组变化较轻,H、B组较为严重,T组较H、B组减轻;(3)血清中炎性因子检测结果显示:①血清中IL-1β的含量,L组、H组、B组、T组均高于A组(P<0.01);随通气时间延长,各组血清中IL-1β的含量明显增加(P<0.01);相同通气时间下,血清中IL-1β的含量H组较L组明显增多(P<0.01),T组较B组明显减少(P<0.05);②血清中TNF-α的含量,L组、H组、B组、T组均高于A组(P<0.01);随通气时间延长,各组血清中TNF-α的含量明显增加(P<0.01);相同通气时间下,血清中TNF-α的含量H组较L组明显增多(P<0.01),T组较B组明显减少(P<0.05或0.01);③血清中IL-8的含量,L组、H组、B组、T组均高于A组(P<0.01);随通气时间延长,各组血清中IL-8的含量明显增加(P<0.01);相同通气时间下,血清中IL-8的含量H组较L组明显增多(P<0.01),T组较B组明显减少(P<0.05或0.01);④血清中IL-10的含量,L组、H组、B组、T组均高于A组(P<0.01);随通气时间延长,各组血清中IL-10的含量明显增加(P<0.05);相同通气时间下,血清中IL-10的含量H组较L组明显增多(P<0.05或0.01),T组较B组明显增多(P<0.01)。
     结论:①VILI大鼠肺间质明显水肿、增宽,大量炎性细胞聚集,肺泡出血,肺泡表面透明膜形成;②相同通气压力条件下,VILI大鼠血清中TNF-α、IL-1β、IL-8、IL-10的含量随通气时间延长而增加;③相同通气时间条件下,VILI大鼠血清中TNF-α、IL-1β、IL-8、IL-10的含量随通气压力升高而增加;④通过IL-10基因转染能够改善VILI大鼠肺组织形态学变化,减轻肺组织水肿及炎性细胞浸润;⑤通过IL-10基因转染能够使VILI大鼠血清中TNF-α、IL-1β、IL-8表达下调,同时IL-10表达上调,从而可以提高肺组织抗炎能力,减轻肺组织损伤。
     目的:探讨全身麻醉机械通气期间体位改变对肺内分流的影响,并观察参附注射液对肺内分流的影响,了解参附注射液的肺保护作用,为临床使用参附注射液提供依据。
     方法:将24例评级为Ⅰ-Ⅱ级的择其行后路脊柱手术的患者随机分为两组,每组12例。其中试验组采用参附注射液1ml/kg进行预注射,对照组不予参附注射液,余处理相同。患者入室后进行血压、心率、血氧饱和度监测。麻醉诱导相同,采用咪达唑仑0.04mg/kg,芬太尼3-4ug/kg,丙泊酚1-1.5mg/kg,阿曲库铵0.6mg/kg或维库溴铵0.1mg/kg进行麻醉诱导,插入加强型气管导管。呼吸机潮气量为8—9ml/kg,频率为12次/分。行左侧桡动脉和右颈内静脉穿刺,监测直接动脉压和中心静脉压。手术期间采用七氟醚和丙泊酚进行麻醉维持。比较两组患者气管插管后30分钟(T_1)及俯卧位后30分钟(T_2)的血压、心率、血氧饱和度、呼气末二氧化碳分压、气道压及肺顺应性的变化,并经桡动脉采血行动脉血气分析,观察动脉血PaO_2及PaCO_2的变化。通过简化的公式计算肺内分流率,Qs/Qt=A-aDO2×0.0031/A-aDO2×0.0031+5A-aDO2=(760-age)×FiO2-(PaGO2×1/0.8)-PaO2(FiO2为1.0)。对所有数据采用SPSS11.5软件包进行统计学处理,检验标准设为0.05。
     结果:(1)两组病人的年龄、性别无统计学差异;
     (2)对照组病人收缩压在两时间点(T_1、T_2)有显著性差异(P<0.01),舒张压无统计学差异(P>0.05);参附组收缩压、舒张压的改变在两时间点均无统计学差异;
     (3)两组病人在不同时间点(T_1、T_2)的氧分压、二氧化碳分压、呼气末二氧化碳分压的改变无统计学意义(P>0.05);
     (4)两组病人在T_1时间点的肺顺应性有统计学差异(P<0.05),在T_2时间点无统计学差异(P>0.05),组内两时间点比较无统计学意义(P>0.05);
     (5)两组病人肺内分流率在T_2时间点较T_1呈现增加的趋势,但无统计学差异(P>0.05)。
     结论:通过本试验可以看出,当病人体位由仰卧位转变成俯卧位以后,肺内分流率呈现一定程度的增加,但无统计学意义;参附注射液用于肺功能正常病人,对病人的血压稳定性及肺顺应性有一定积极作用,但对肺内分流率改变未见明显影响。
Objective:Mechanical ventilation(MV)is widely used in anesthesiology,critical care medicine,emergency,IntMED and so on,but at the same time,ventilator-induced lung injury effects prognosis for severe patients.The experiment takes molecular biology technique, gene transfect IL-10 to lung tissue to inhibit the releasing,of cytokine and phlegmonosis medium in VILI.The experiment is to evaluate the treatment from observing TNF-α,IL-1β,IL-8,IL-10 and changes of morphology in lung tissue.At last,it will offer a theory for clinic to prevent and cure VILI.
     Methods:54 male SD(Sprague Dawley)rats were randomly divided into 9 groups,6 every group.Group A:control group(have no deal);Group L:low airway pressure(15cmH_2O),it divided to L_2 and L_4,depending on time of mechanical vetilation; Group H:high airway pressure(25cmH_2O),it divided to H_2 and H_4,depending on time of mechanical vetilation;Group B-.Ad-Blank gene transfection(25cmH_2O),it divided to B_2 and B_4,depending on time of mechanical vetilation;Group T:ADS-h-IL-10 gene transfection(25cmH_2O),it divided to T_2 and T_4,depending on time of mechanical vetilation. The experimental rats were injected with 10%chloraldurat(0.3g/kg)at abdominal cavity,and then cut-off trachea at the middle of neck.After inserting tracheal catheter and connecting breathing machine,open the pectoral cavity at lefe side between 3,4 cervical ribs,inject agentia from right ventricle.The agentia is respectively:Lactic Acid for groupL,H;Ad-Blank for group B;AD5-h-IL-10 for group T(all groups is 0.1ml).Close the pectoral cavity,removal tracheal catheter and intramuscular injection penicillin 10~5U to prevent infection.After 48 hours,recut-off trachea and insert tracheal catheter to give a persistent mechanical ventilation.In the process,boost 10%chloraldurat rely on your need.For the reservative time,open the abdominal cavity,collect blood from abdominal aorta. Then centrifugalization the blood at rate of 3000r/min for 15min,collect supernatant fluid to preserced in refrigerator(-80℃).Take lung tissue to detect pathology change.At last,detet the contents of TNF-α,IL-1β,IL-8,IL-10 in blood serum.All the data were analyzed by SPSS11.5 statistics software,P value<0.05 was considered to have statistical significance.
     Result:(1)Light microscope HE:Group A:pulmonary alveoli are as normal;Group L:there is a little effusion in pulmonary alveoli and some phlegmonosis cell besides the blood vessel;the extent aggregate with mechanical ventilate time;Group H and B is serious than L and T is lessen;(2)Electron microscope:Group A:structure of cellⅠ,Ⅱand endotheliocyte are as integrity as normal;Group L,H,B,T:bioblast swell、ablate and its crista disappear,endoplasmic broaden,cell nucleus enlarge,bland between cell nucleus and cell-substane broaden,caryotin bad-distribute,lamellar body swell,microvilli decrease with different degree;the change is not obvious;compared with group H and B,T is lessen in some entent;(3)Inflammatory factors from blood serum:①Content of IL-1β:Group L,H,B,T is higher than group A(P<0.01);content of IL-1βhighten with time prolong(P<0.01);with the same ventilation time,H is higher than L(P<0.01)and T is lower than B(P<0.05);②Content of TNF-a:Group L、H、B、T is higher than group A(P<0.01);content of TNF-ahighten with time prolong(P<0.01);with the same MV time,group H is obvious ly higher than group L(P<0.01)and group T is lower than group B(P<0.05 or 0.01);③Content of IL-8:Group L,H,B,T is higher than group A(P<0.01); content of IL-8 highten with time prolong(P<0.01);with the same MV time,group H is obviously higher than group L(P<0.01)and group T is lower than group B(P<0.05 or 0.01);④Content of IL-10:Group L,H,B,T is higher than group A(P<0.01);content of IL-10 highten with time prolong(P<0.01);with the same MV time,group H is obviously higher than group L(P<0.05 or 0.01)and group T is higher than group B(P<0.01).
     Conclusioa:(1)VILI rats intertitium of lung edema、widen and many phlegmonosis cell collect,pulmonary alveoli bloodloss and form hyaline membrane in the surface;(2)At the same airway pressure,content of TNF-α,IL-1β,IL-8,IL-10 enhance with the time prolong;(3)With the same time of mechanical ventilation,content of TNF-α,IL-1β,IL-8,IL-10 enhance with the highten of airway pressure;(4)IL-10 gene tramsfection can amendment morphology change of lung tissue,lessen edema and infiltration of phlegmonosis cell;(5)IL-10 gene transfection down regulation the expression of TNF-α,IL-1β,IL-8 in blood serum and up regulation IL-10 to enhance the ability to anti-phlegmonosis,at last to lessen injury of lung.
     Objtctive:Approach influence on lung shunt fraction from changes of body position during general anaesthesia.Observing the influence of shenfu injection on lung shunt fraction,and comprehend the function of shenfu injection on protection of lung,at last provide an evidence for the use of shenfu injection in clinic.
     Methods:24 patients(ASAⅠ-Ⅱ)for back bone selective operation were randomly divided into 2 groups,12 every group.The experimental group give shenfu injection intravenously,with the dose of 1ml/kg.Monitoring BP,HR,SpO_2 after the patients in.All the patients use the same drug in induction of anaesthesia,including midazolam0.04mg/kg,fentanyl 3-4ug/kg,propofol 1-1.5mg/kg,atracurium 0.6mg/kg or vecuronium 0.1mg/kg.Aftering intubate the catheter,set the V_T 8-9ml/kg,rate is 12/min.Punct the left radial artery and right internal jugular vein to moitor BP and CVP.We use sevoflurane and propofol to maintenance anesthesia.Compared the BP、HR、SpO_2、P_(ET)CO_2、Raw and C_(dyn)at T_1(30min of supine position)and T_2(30min of prone).Cull blood from radial artery at two time point and do blood gas analysis.Compare the change of PaO_2 and PaCO_2.Calculate lung shunt fraction from the formula:Qs/Qt:=A-aDO2×0.0031/A-aDO2×0.0031+5 A-aDO2=(760-age)×FiO2-(PaCO2×1/0.8)-PaO2(FiO2为1.0).All the data were analyzed by SPSS11.5 statistics soflware,P value<0.05 was considered to have statistical significance.
     Result:(1)Patients in two groups have no difference in age and sex.;
     (2)SBP in patients of control group have significant difference at T_1、T_2(P<0.01),DBP have no difference at T_1、T_2;
     (3)PaO_2、PaCO_2 and P_(ET)CO_2 have no difference in two groups at T_1、T_2(P>0.05);
     (4)Cydn in two groups at T_1 time point have difference(P<0.05)and T_2 have no difference.In the same group,there is no difference at two time points(P>0.05);
     (5)Lung shunt fraction present a tendency of rising,but have no difference in statistics(P>0.05).
     Conclusion:We can conclude that from the study,lung shunt fraction present a tendency of rising,but have no difference in statistics when the patients from supine position to prone position;shenfu injection has a function in sustaining the blood pressure and lung compliance during anaesthesia,but have no significant influrance on lung shunt fraction to health adult.
引文
1.Schnapp LM,Chin DP,Szaflarski N,et al.Frequency and ipmportant of barotraumas in 100 pattients with acute lung injury.Crit Care Med,1995;23(2):272.
    2.Singh JM,Stewart TE.High-frequency mechanical ventilation principles and practices in the era of lung-protective ventilation strategies.Respir Care Clin N Am,2002;8(2):247-260.
    3.Lista G,Colnaghi M,Castoldi F,et al.Lung injury and ventilatory strategies.Pediatr MedChir,2003;25(1):35-41.
    4.Guekan OU,Donnell C,Brower R,et al.Differential effects of mechanical ventilatory strategy on lung injury and systemic organ inflammation in mice.Am J Physiol Lung Cell Mol Physiol,2003;285(6):L710-L718.
    5.Kolb M,Margetts PJ,Anthony DC,et al.Transient expression of IL-1β induces acute lung injury and chronic repair leading to pulmonary fibrosis.Clin Invest,2001;107(2):529.
    6.姜丽岩,何礼贤.白介素-8与肺部炎症反应.国外医学呼吸系统分册,1999;19(2):82-84.
    7.Vlahakis NE,Schroeder MA,Limper AH,et al.Stretch induces cytokine release by alveolar epithelial cells in vitro.Am J Physiol,1999;277(1):L167-173.
    8.Yokoyama T,Sekiguchi K,Tanaka T,et al.Angiottensin Ⅱ and mechanical stretch induce production of tumor necrosis factor in cardiac fibroblasts.Am J physiol,1999;276(6):H1968-1976.
    9.Okada M,Matsumori A,Onok,et al.Cyclic stretch upregulates production of interlcukin-8 and monocyte chemotactic and actibating factor/monocyte chemoatlractant protein-1 in human endothelian cells.Arterioscler Thromb Vasc Biol,1998;18(2):894-901.
    10.Tremblay L,Valenza F,Ribeiro SP,et al.Injurious ventilatory strategies increase cytokines and c-fos m-RNA expression in an isolated rat lung model.Clin Invest,1997;99(5):944-952.
    11.Von Bethmann AN,Brasch F,Nusing R,et al.Hyperventilation induces release of cytokines from perfused mouse lung.Am J Respir Crit Care Med,1998;157(3):263-272.
    12.Takata M,Abe J,Tanzka H,et al.Intraalveolar expression of tumor necrosis factor-alpha gene during conventional and hige-frequency ventilation.Am J Respir Crit Care Med,1997;153(6):272-279.
    13.Pagel PS,Fu JL,Damask MC,et al.Desflurane and isoflurane produce similar alterations in systemic and pulmonary hemodynamics and arterial oxygenation in patients undergoing one-lung ventilation during thoracotomy.Anesth Analgk,1998;87(4):800-807.
    14.Simonson 9G,Huang YC,Fracica PJ,et al.Changes in the lung after prolonged positive pressure ventilation in mormal baboons.J Cirt care,1997;12(2):72-82.
    15.李惠芳,张梅,杨林,等.吸入不同浓度氧全麻下肺叶手术时氧自由基及肺超微结构的变化.中华麻醉学杂志,1997;17(6):357-360.
    16.Ranieri VM,Ster PM,T rtorella et al.Effect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome:a randomized controlled trial.JAMA,1999;282(1):54-61.
    17.马武华,吴一龙,李朝霞.乌司他丁对化疗后肺叶切除术病人肺的保护作用.中华麻醉学杂志,2006;2(1):39-42.
    18.Spragg RG,Smith RM.Pathology of the surfactant system of the mature lung.Am J Respir Crit Care Med,1997;155(2):756-760.
    19.Gutierrez JA,Ertsey R,Scavo LM,et al.Mechanical distention modulates alveolar epithelial cell phenotypic expression by transcriptional regulation.Am J Respir Crit Care Med,1999;21(2):223-229.
    20.Sanchez-Esteban J,Tsai SW,Sang J,et al.Effects of mechanical forces on lung-specific gene expression.Am J Med Sci,1998;316(3):200-204.
    21.Veldhuizen RA,,Marcou J,Yao Lijuan,et al.Alveolar surfactant aggregate conversion in ventilated normal and injured rabbits.Am J Physiol,1996;270(1):L152-158.
    22.朱光发,宋承娟,周新,等.呼吸机所致肺损伤的发生机制.国外医学呼吸系统分册,2000;20(2):91-93.
    23.Ito Y,Veldhuizen RA,Yao LJ,et al.Ventilation strategies affect Surfactant aggregate conversion in acute lung injury.Am J Respir Crit Care Med,1997;155(2):493-499.
    24.Thomassen MJ,A tal JM,Dvis LT,et al.Regulation of human alveolar macrophage inflammatory cytokines by Tyloxapol:A component of the synthetic surfactant exosurf.Clin Immuonpathol,1995;7(2):201-205.
    25.Zhamg H,Sutsky AS,Vncent JL.Oxygen free radicals in ARDS.septic shock and organ dysfunction.Intensice Care Med,2000;2(4):474-476.
    26.Metnitz PG,Brtens C,Fscher M,et al.Antioxidant status in patients with acute respiratory distress syndrome.Intensive Care Med,1999;25(5):180-185.
    27.Peterson MW,Krschbaum JA.Bestos-induced lung epithelial permeability potential role of nonoxidant pathways.Am J Physiol,1998;275(4):L262-268.
    28.孟激光,段蕴铀.急性肺损伤及急性呼吸呼吸窘迫综合征机械通气治疗进展.海 军总医院学报,2006;19(4):232-236.
    29.俞森洋.急性呼吸窘迫综合征的机械通气策略和方法.中华医学杂志,2001;81(8):511-512.
    30.陈振岗.机械通气相关肺损伤与肺保护性策略.河北医学,2003;9(12):1127-1129.
    31.Amato MB,Barbas CS,Medeiros DM,et al.Benificial effects of the "open lung approach"with low distending pressure in acute respiratory distress syndrome.A prospective randomized study on mechanical ventilation.Am J Respir Cirt Care Med,1995;182(8):1835-1846.
    32.Amato MB,Barbas CS,Medeiros DM,et al.Effect of a prospective ventilation strategy on mortality in the acute respiratory distress syndrome.N Engl Med,1998;338(5):385-387.
    33.张新日,阚为民,徐永健,等.通气机相关性肺损伤防治进展.国际呼吸杂志,2006;26(4):296-298.
    34.肖军.机械通气损伤机理及相关保护性通气策略.华夏医学,2001;2(14):245-237.
    35.陈惠香,谢俊然.呼吸机所致肺损伤的炎症机制与治疗进展.国外医学麻醉学与复苏分册,2003;24(3):187-190.
    36.冯丹,姚尚龙,武庆平,等.酪氨酸蛋白激酶抑制剂对大鼠呼吸机所致肺损伤的保护作用.中国药理学通报,2007;23(3):370-373.
    37.姜兴权,宋德彪,刘海波,等.痰热清注射液对机械通气患者肺保护作用的临床研究.中国中西医结合急救杂志,2006;13(21):80-82.
    38.Pajkrt D,Camoglio L,Tiel-van Buul MC,et al.Attenuation of proinflammatory response by recombinant human IL-10 in human endotoxemia:effect of timing of recombinant human IL-10 administration.J Immunol,1997;158(8):3971-3977.
    39.Schottelius AJ,Mayo MW,Sartor RB,et al.Interleukin-10 signaling blocks inhibitor of kappa B kinase activity and nuclear factor kappa B DNA binding.Biol Chem,1999;274(45):31868-31874.
    40.OLszyna DP,Pajkrt D,Lauw FN,et al.Interleukin 10 inhibits the release of CC chemokines during human endotoxemia.Infect Dis,2000;181(2):613-620.
    41.Tashiro H,Shinozaki K,Yahata H,et al.Prolongation of liver allograft survival after interleukin-10 gene transduction 24-48 hours before donation.Transplantation,2000;70(2):336-339.
    42.Lindsay J,Van Montfrans C,Brennan F,et al.IL-10 gene therapy prevents TNBS-inducedcolitis.Gene Ther,2002;9(24):1715-1721.
    43.Okada M,Matsumori A,Onok,et al.Cyclic stretch upregulates production of interlcukin-8 and monocyte chemotactic and actibating factor/monocyte chemoatlractant protein-1 in human endothelian cells.Arterioscler Thromb Vasc Biol,1998;18(2):894-901.
    44.Tremblay L,Valenza F,Ribeiro SP,et al.Injurious ventilatory strategies increase cytokines and c-fos m-RNA expression in an isolated rat lung model.Clin Invest,1997;99(5):944-952.
    45.Pagel PS,Fu JL,Damask MC,et al.Desflurane and isoflurane produce similar alterations in systemic and pulmonary hemodynamics and arterial oxygenation in patients undergoing one-lung ventilation during thoracotomy.Anesth Analgk,1998;87(4):800-807.
    46.Spragg RG,Sith RM.Pathology of the surfactant system of the mature lung.Am J Respir Cirt Care.Med,1997;5(2):756-760.
    47.Zhamg H,S,utsky AS,Vncent JL.Oxygen free radicals in ARDS septic shock and organ dysfunction.Intensice Care Med,2000;142(2):474-476.
    48.Imanaka H,Shimaoka M,Matsuura N,et al.Ventilator-induced lung injury is associated with neutrophil infiltration,maerophage aetivatio,and TGF-α mRNA upregulation in rat lungs.Anesth Analg,2001;92(2):428-436.
    49.Matthay M A,immerman G A.Acute lung injury and the acute respiratory distress syndrome:four decades of inquiry into pathogenesis and rational management.Am J Respir Cell Mol Biol,2005;33(4):319-27.
    50.李丽,王兆铖.损伤后的免疫功能改变和进展.国外医学免疫学分册,1998;21(31):157-159.
    51.Santos CC,Han B,Andrade CF,et al.DNA microarray analys is of gene expression in alveolar epithelial cells in response to TNFalpha,LPS and cyclic stretch.Physiol Genomics 2004;19(3):331-342.
    52.Russell WC.Update on adenovirus and its vectors.J Gen Virol,2000;81(4):2573-2604.
    53.Miao W,Luo Z,Kisis RN,et al.Intracoronary adenovirus-mediated Akt genge transfer in heart limits infart size following ischemia-reperfusion injury in viro.J Mol Cell Cardiol,2000;32(2):2397-2402.
    54.Opal SM,Wherry JC,Grint P,et al.Interleukin 10 potential benefits and possible risks in clinical infectious diseases.Clin Inle t Dis,1998;27(2):1495-1507.
    55.Pters AH,Drumm J,Ferrell C,et al.Absence of germline infection in male mice following intraventricular injection of adenovirus.Mol Ther,2001;4(2):603-613.
    56.毛佳,马雪梅,张栋.供肝转染IL-10对大鼠肝脏移植术后排斥反应的影响.临床和 实验医学杂志,2005;4(2):65-68.
    57.刘辰,吴孟超,张柏和,等.人白介素-10腺病毒转染对大鼠肝缺血再灌注损伤的保护作用.中华普通外科杂志,2006;21(1):62-64.
    58.陈家存,马腾骧,畅继武.逆转录病毒载体介导白细胞介素10基因转染对移植物保护作用.中华实验外科杂志,2003;20(12):1127-1128.
    59.Mulligan MS,Vaporeiyan AA,Mryasala M,et al.Tumor necrosis factor alpha regulates in vivo intrapulmonary expression of ICAM-1AM.Pathol,1993;142(6):1739-1749.
    60.Hans G,Folkesson,Michael A,et al.Aeid aspiration induced lung injury in rabbits is mediated by interleukin--8-dependent mechanisms.J Clin Invest,1995;96(3):107-114.
    61.Pittet JF,Machersie RC,Martin TR,et al.Biological markers of acute lung injury.prognostic and pathogeneti significance.Am J Respir Crit Care Med,1997;155(4):1187-1205.
    62.Hou J,Baichwsl Vand,Cao Z.Regulatort elents and transcription factors controlling basal and cytohine-induced crpression of the gene eccoding ICAM.Proc Nail Acad Sci USA,1994;91(2):1641-1650.
    63.张青,李琦,毛宝龄,等.油酸-内毒素致伤大鼠肺组织TNF-α、IL-1β、IL-6和IL-4、IL-10、IL-13的mRNA表达.解放军医学杂志,2004;29(9):795-797.
    64.Goodman RB,Dugin J,Lee JS,et al.Cytokine-mediated inflammation in ALI.Cytokine Growth Factor Rev,2003;14(5):523-535.
    1.Slinger P,Triolet W,Wilson J.Improving arterial oxygenation during one-lung ventilation.Aneathesiology,1988;68(2):291-295.
    2.Page1 PS,Fu JL,Damask Me,et al.Desflurane and isoflurane produce similar alterations in systemic and pulmonary hemodynamics and arterial oxygenation in patients undergoing one-lug ventilation durig thoracotomy.Aneth Analg,1998;87(4):800-7.
    3.孙颖,冯艺,杨拔贤,等.不同麻醉长时间单肺通气对肺内分流和氧合的影响.中华麻醉学杂志,2004;24(5):339-344.
    4.冯艺,孙颖,杨拔贤.硬膜外阻滞对全麻单肺通气肺内分流和氧合的影响.中华麻醉学杂志,2002;22(3):143-147.
    5.孙震,龙圣武,吕晶,等.两种麻醉方法下食道癌根治术患者单肺通气期间肺内分流的比较.中华麻醉学杂志,2006;26(2):110-113.
    6.周礼湘,周清河,肖旺频,等.瑞芬太尼复合异丙酚靶控输注对单肺通气时血液氧合及肺内分流的影响.中华实验外科杂志,2006;23(10):1251-1254.
    7.Maseda F,Vilchez E,Delcampo JM,et al.Hypoxic pulmonary vasoconstriction during one-lung ventilation in the lateral decubitus position and thoracic anesthesia.Br J Anaesth,1995;74(4):152.
    8.Ignacio G,Begona Q,Luis O,et al.Arterial oxygenation during one-lung ventilation;combined versus general anesthesia.Anesth Analg,1999;88(5):494.
    9.Ishibe Y,Shiokawa Y,Umeda T,et al.The effect of the racic epidural anesthesia on hypoxic pulmonary vasoconstriction in dogs;an analysis of the pressure flow curve.Anesth Analg,1996;82(2):1409-1055.
    10.Groh J,Kuhnle GE,Schell A,et al.Isoflurane inhibits hypoxic pulmonary vasoconstrictiono An in vivo fluorescence,microscopic study in rabbits.Anethesiology,1994;81(4):1436-1444.
    11.王剑,李伟,李毅,等.下胸段硬膜外阻滞在单肺通气期间对肺内分流的影响.岭南急诊医学杂志,2004;9(4):277-279.
    12.安珂,董铁立,王春亭.单肺通气期间胸部硬膜外麻醉对肺内分流的影响.实用医学进修杂志,2004;32(3):174-176.
    13.林文前,李伟,曾维安,等.全麻复合硬膜外阻滞对单肺通气期间肺内分流的影响.临床麻醉学杂志,2002;18(3):121-123.
    14.陈士寿,陈燃,曾一平,等.单肺通气期间体位对血液氧合的影响.临床麻醉学杂 志,2006;22(3):193-195.
    15.Marshshall BE.Continuity of response to hypoxi pulmonary vasoconstriction.J Appl Physiol,1980;49(3):189-196.
    16.Voelkel NF.Mechanisms of hypoxic pulmonary vasoconstriction.Am Rev Resp Dis,1986;133(2):1186-1195.
    17.Lerman A,Hildebrand JR,Aarhus LL,et al.Endothelin has biological actions at pathophysiological concentrations.Circulational,1991;3(5):1808-1814.
    18.吴国明.前列腺素E_1在肺疾病中的应用.国外医学呼吸系统分册,1990;10(3):725-728.
    19.胡明伦,张东琦,金烈烈.单肺通气期间超声雾化吸入前列腺素E_1对肺内分流和氧合的影响.中华麻醉学杂志,2003;23(4):305-307.
    20.岳子勇,宋春雨,李文志.雾化吸入前列腺素E_1对急性肺损伤猪氧合及肺内分流的影响.中华麻醉学杂志,2006;26(5):435-437.
    21.王家和,成文聪,张炳熙.鼻内窥镜手术患者硝普钠控制性降压期间肺内分流的变化.中华麻醉学杂志,2006;26(6):501-503.
    22.陈淑娟,张海明,李荧,等.肺心病急发期患者肺内分流变化的临床研究.实用临床医药杂志,2003;7(6):126.
    23.赵学群,张毅,陶家驹.慢性肺心病肺内分流的探讨.职业与健康,2001;17(7):100-101.
    24.夏炎兴.参附注射液对培养搏动的影响.中西医结合杂志,1987;11(7):679.
    25.邵丰,郑世营,赵军,等.参附注射液对兔离体肺缺血/再灌注保护作用的实验研究.中国急救医学,2006;26(3):195-197.
    26.艾宇航,彭鎏,张丽娜.参附注射液对内毒素所致肺损伤的保护作用.中国急救医学,2006;26(4):285-286.
    27.Litt MD.A model of pain and anxiety associated with acute stressors;distress in procedures.Behav Res Ther,1996;34(6):459.
    28.Smith TA.The prevalence of dental from in rural areas.Dent Res(Special Issue),1991;5(2):55.
    29.Berggren U,Meynert G.Dental fear an avoidance:causes,symptoms,and consequences.Am Dent Assoc,1984;109(2):247-251.
    30.郭莲怡,刘仁光.参附注射液对兔心肌缺血再灌注所致肺损伤的保护作用.中国中医急诊症,2003;12(4):349-350.
    31.陈东辉,李东晓,李兴平,等.参附注射液增强机体非特异性抵抗力作用研究.中国中医急症,2003,12(2):153-154.
    32.任桂花,牛平,刘红丽.参附注射液治疗慢性阻塞性肺疾病疗效观察.现代中西医 结合杂志,2006;15(16):2160.
    33.李翔敏,翟同钧.参附注射液对老年肺心病急性发作期心肺功能的影响.重庆医学,2006;35(13):1219-1220.
    34.吴万垠,王斌,张海波,等.参附注射液对NP方案治疗非小细胞肺癌减毒作用的临床研究.新中医,2006,38(10):20-23.
    35.荣震,莫春梅.参附注射液治疗恶性肿瘤患者肺念珠菌病30例疗效观察.中国中医急症,2006;15(2):152-154.
    36.顾晓明,殷俊,王乔中.参附注射液对55例心力衰竭病人心功能影响的分析.中西医结合脑血管病杂志,2005;3(5):389-390.
    37.茹海港.参附注射液治疗慢性肺心病心衰疗效观察.浙江中医杂志,2002;37(3):134.
    38.陈志强,洪涛,赖颢,等.参附注射液治疗二尖瓣替换术后心功能不全的疗效观察.中国临床医学,2003;10(2):178-179.
    39.李菊香,王铅珍.参附注射液治疗慢率室性早搏疗效观察.中国中西医结合杂志,2002;22(5):394.
    40.祝红明.参附注射液治疗心动过缓35例临床观察.太原医刊,2004;31(9):345.
    41.张薇.参附注射液治疗病态窦房结综合征疗效观察.浙江中西医结合杂志,2004;14(2):97-98.
    42.万琪琳,张媛,刘玉茹.参附注射液治疗急性心肌梗死合并缓慢性心律失常44例.中国新药杂志,2003;12(7):563-564.
    43.陈瑛.参附注射液治疗慢性肺源性心脏病的临床观察.现代中西医结合杂志,2004;13(1):46-47.
    44.孟志萍,顾晓明,吴金根,等.参附注射液治疗急性病毒性心肌炎43例.中西医结合心脑血管病杂志,2005;3(7):644.
    45.吴昊,贺凤义,陈焕春.参附注射液治疗稳定型心绞痛的研究.现代中西医结合杂志,2004;13(16):2124-2125.
    46.董辉,熊利泽,陈敏.参附注射液对冠脉架桥术患者心功能的保护作用.中国康复,2004;19(1):12.
    47.杨国锋,廖崇先,陈良万,等.参附注射液在心脏手术中对心肌的保护作用.中国中西医结合杂志,2003;23(1):7.
    48.董辉,熊利泽,陈敏,等.参附注射液对心脏瓣膜置换术中患者心功能的保护研究.中国中西医结合杂志,2004;24(1):32.
    49.王培红,张建芳.参附注射液治疗慢性肾功能不全近期疗效观察.中华临床医学实践杂志,2003;2(7):632-633.
    50.赵宁,王鸣,等.参附注射液对早期糖尿病肾病患者血液D-D二聚体、Fib、CRP 的影响.浙江中西医结合杂志,2007;17(8):476-478.
    51.魏湘华,邹江,等.参附注射液在肿瘤病人使用异丙酚麻醉诱导期间的循环稳定作用.四川肿瘤防治,2002;15(3):147-149.
    52.庄心良,曾因明,陈伯銮,等.现代麻醉学第3版,北京:人民卫生出版社,2005,3:61.
    53.缪长虹,桂小平.低氧性肺血管收缩研究现状.国外医学麻醉与复苏分册,1995;16(1):6-7.
    54.Winer CM,Kir W,Albert PK.Prone position reverses gravitational distribution of perfusion in dos lung with oleic acid-induced injury.J Appl physiol,1990;68(2):1386-1392.
    55.Mutoh T,Guest RJ,Lamn WJE,et al.Prone position alters the effect of volume overload on regional pleural pressures and improves hyposemia in pigs in vivo.Am Rev RespirDis,1992;146(6):300-306.
    56.Albert RK,Hubmayt RD.The prone position eliminates compression of the lungs by the heart.Am J Respir Cirt Care Med,2000;161(5):1660-1665.
    57.Martin TJ.Critical care medicine in AJMCCM 2000.Am J Respir Crit Care Med,2001;164(8):1347-1361.
    58.Mure M,Glenny RW,Dom ino KB,et al.Pulmonary Gas Exchange improves in the Prone Position with Abdominal Distension.Am J Respir Crit Care Med,1998;157(2):1785-1970.
    59.Albert RK,Hubmayr.The prone position elminates compression of the lungs by the heart.Am J Respir Crit Med,2000;161(4):1660-1665.
    60.付克广,赵施竹,段庆红,等.仰卧作俯卧位心脏对肺压迫作用的CT探讨.放射学实践,2002;17(5):412-413.
    61.Malboission LM,Busch CJ,Puybasser L,et al.Role of the heart in the loss of aeration characterizing lower lobes in acut respitatory distress syndrome CT scan ARDS study group.Am J Respir Cirt Care Med,2000;161(10):2005-2012.
    62.Wiener CM,M ckem a WJ,M yers MJ,et al.Left lower lobe ventilation is reduced in patients with cardiom egly in the supping but not in the prone pwsition.Am Rev Respir Dis,1990;141(1);150-155.
    63.崔晓宁,朱传耘.参附注射液在全麻诱导期间的循环稳定作用观察.实用医技杂志,2004;11(6):916-917.
    64.李扬,熊利泽,秦绪军,等.参附注射液对幕上肿瘤手术患者血清SOD活性和MDA 含量的影响.第四军医大学学报,2003;24(16):1507-1509.
    65.罗自强,冯丹丹,邱少杰,等.参附注射液对肺组织肺泡表面活性物质合成的影 响.湖南医科大学学报,2003;28(2):137-140.
    66.刘先我,邹捍东,余金甫,等.参附注射液对缺血再灌注家兔多脏器损伤的治疗作用.中华麻醉学杂志,1997;17(7):430-432.
    67.刘欣,刘先义,夏中元,等.参附注射液对大鼠缺血再灌注小肠细胞Bax、Bcl-2及c-myc蛋白表达的影响.江西医学院学报,2004;44(1):5-8.

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700