乌司他丁在经皮体外循环中对犬心肌的保护作用
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摘要
目的研究乌司他丁(Ulinastatin,UTI)应用于经皮体外循环(Percutaneous cardiopulmonary support system,PCPS)中对犬心肌组织中细胞间黏附分子-1(Intercellular adhesion molecule,ICAM-1)表达的影响及其对心肌的保护作用。方法试验用杂种犬20只,随机平均分为乌司他丁实验组(U组)和对照组(C组),每组各10只。U组在PCPS预充液中加1万U/ kg UTI ,并于PCPS转机开始前即经静脉再给1万U/ kg UTI持续滴注。C组常规建立PCPS并转机。分别于PCPS转机前10 min(A时点)和PCPS转机后60 min(B时点)两个时点,切取犬心肌右心耳组织,检测心肌组织ICAM-1表达量及心肌组织中超氧化物歧化酶(Superoxide dismutase,SOD)、丙二醛(Maleic dialdehyde,MDA)、乳酸(Lactic acid,LA)、三磷酸腺苷酶(Adenosine triphosphate,ATPase)的水平。并记录PCPS建立时间、主动脉阻断时间、主动脉灌注时间、经皮体外循环转机时间、心脏复跳情况。结果两组实验犬心肌组织中,ICAM-1的表达量在B时点较A时点均明显增高,但在B时点U组ICAM-1表达量低于C组(P<0.05); LA和MDA的含量在B时点均明显高于A时点,但在B时点U组LA和MDA的含量均低于C组(P<0.05);SOD和ATPase的活力在B时点均低于A时点,但在B时点U组SOD和ATPase的活力高于C组(P<0.05)。结论PCPS时,心肌组织的缺血-再灌注损伤可引起心肌组织ICAM-1表达上调,心肌组织中LA和MDA含量增高,SOD和ATPase活力降低。应用乌司他丁可抑制心肌组织中ICAM-1的表达,减少心肌组织中LA和MDA的产生,降低SOD和ATPase的消耗,从而减轻心肌的炎症反应,进而保护心肌组织。
Objective To investigate the expression of intercellular adhesion molecule-1(ICAM-1) in canine myocardium during the PCPS, evaluate whether ulinastatin could influence its expression and the protective effect on myocardium. Methods Twenty dogs were randomly and medially divided into two groups: ulinastatin group(UG) and control group (CG)。In ulinastatin group (U n =10) dogs received ulinastatin 20000 unit·kg-1, half was added into the PCPS priming fluid, and another half was given by intravenous injection before PCPS running. In control group(C n=10) dogs received PCPS conventionally, the same volume of saline instead of ulinastatin. Right atrial appendage of the dog was obtained by the time of 10 minitures before PCPS running (point A) and 60 minitures after PCPS running (point B). The expression of ICAM-1 in cardiac myocytes and the levels of SOD、MDA、LA、ATPase in canine myocardium were detected. And meantime we recorded the establishment and running time of PCPS、aortic corss–clamp time、heart re-beat.
     Results The expression of ICAM-1 in myocardial tissue after PCPS in both groups increased and it was higher in control group than that in ulinastatin group (P <0.05).The levels of LA and MDA in myocardial tissue after PCPS in both groups increased and they were higher in control group than that in ulinastatin group (P<0.05). The levels of SOD and ATPase in myocardial tissue after PCPS in both groups decreased and they were higher in ulinastatin group than that in control group (P<0.05). Conclusion Myocardial ischemical reperfusion injury can cause the expression of ICAM-1 in myocardium highly up-regulating, the levels of LA and MDA in myocardial tissue increasing, SOD and ATPase decreasing.Ulinastatin can restrain the expression of the ICAM-1 ,reduce the productions of LA and MDA, and decrease the consumption of SOD and ATPase in myocardial tissue during the PCPS,thus protecting the myocardial tissue by inhibiting the myocardial inflammation.
引文
1. Phillips SJ , Ballentine B , Slonine D ,et a1. Percutaneous initiation of cardiopulmonary bypass[J ] . Ann of Thorac Surg ,1983 ,36(2) :223 - 5.
    2.卢苇,曾建业.经皮穿刺体外循环在危重病急救中的应用.广西医学,2008,30:395-8.
    3.李海林,金素平,葛根贤等.经皮穿刺急诊体外循环心肺复苏的实验与临床研究.中华急诊医学杂志,2005,14:328-30.
    4. Huang PZ, Zhou GH, Xue J, et al.Laboratory observation of resuscitation by cardiopulmonary bypass after prolonged cardiac arrest in dogs.Emerg Med,1997,6(1):7-9
    5. You QJ, Shen ZY, Jiang XC, et al.Application of emergency cardiopulmonary bypass in ordinary chest surgery.Chin J Emerg Med,2003,12(11):781.
    6. Li ZD, Jing H, Niu DM, et al.Clinical application of emergency extracorporeal circulation. J Med Postgrad,2003,16(11):831-2.
    7. Shigeru Kato,Shin-ichiro Morimoto,Shinya Hiramitsu,et al. Use of Percutaneous Cardiopulmonary Support of Patients With Fulminant Myocarditis and Cardiogenic Shock for Improving .Am J Cardiol.1999 Feb 15;83(4):623-5,A10.
    8.吴华,刘亚湘,毛向辉等.经皮心肺支持急救重症暴发性心肌炎.中国体外循环杂志,2004,4(2):220-1.
    9. Fukumoto H, Nishimoto T, Morita H, et al . Emergency application ofpercutaneous cardiopulmonary support system[J ] . The Japanese Journal of Acute Medicine , 1994 , 18 (13) :1869.
    10.张虹儿,周淑萍,贺宏艳等.急诊心血管手术中的体外循环管理.Modem Practical Medicine,2009,21:538
    11. Naoyoshi Aoyama,MD;Tohru Izumi,MD;Katsuiko Hiramori,MD;et al.National Survey of Fulminant Myocarditis in Japan-Therapeutic Guidelines and Long-Term Prognosis of Using Percutaneous Cardiopulmonary Support for Fulminant Myocarditis[J].Circ J,2002,66:133-44.
    12.王素芬,方玉桂.1例重症心肌炎患者经皮心肺支持救治的护理.南方护理学报,2003,10:78.
    13.龙村主编.体外循环血[M].第1版.北京:人民军医出版社,2004:475-97.
    14. Elliott M J , Finn AH. Interaction between neutrophils and endothelium. Ann Thorac Surg, 1993, 56: 1503~8.
    15.张凤伟,吴树明,邢西忠等.二尖瓣置换术患者ICAM-1变化及乌司他丁的抑制作用.山东医药,2003,43:13-4.
    16. Gibbon JH .Application of a mechanical heart and lung apparatus to cardiac surgery.Minn Med,1954,37:171.
    17.韩秀珍,焦波,尚雪原,等.低分子量肝素对白细胞粘附和粘附分子表达的影响[J].中国生化药物杂志,2003,24(4):179-81.
    18. Pees C ,Haas NA, vonder Beek J,et al.Cardiac troponin I is increased after interventional closure of atrial septal defects [J].Cathet Cardiovasc Int,2003,58(1):124-9.
    19. Rode`s-Cabau J,Palacios A,Palacio C,et al.Assessement of the markers of platelet and coagulation activation following transcatheter closure of atrial septal defects [J].International Journal of Cardiology,2005,98(1):107-12.
    20.邓军,孔祥清,杨荣等.室间隔缺损介入治疗前后可溶性细胞间粘附分子-1、P选择素、肌钙蛋白I的变化及意义[J].南京医科大学学报,2005,25(8):555-7.
    21. Jennings RB, Sommers HM,Smyth GA,et al. Myocardial necrosis induced by temporary occlusion of a coronary artery in the dog. Arch Pathol. 1960 Jul;70:68-78.
    22. Bulkley BH, Hutchins GM. Accelerated "atherosclerosis". A morphologic study of 97 saphenous vein coronary artery bypass grafts. Circulation. 1977 Jan;55(1):163-9.
    23.金慧铭,王建枝主表.病理生理学.第6版.北京:人民卫生出版社,2004:201-13.
    24. Marcia G. Tonnesen,Donald C. Anderson,Timothy A. Springer,et al.Adherence of Neutrophils to Cultured Human Microvascular Endothelial Cells Stimulation by Chemotactic Peptides and Lipid Mediators and Dependence upon the Mac-1, LFA-1, p150,95 Glycoprotein Family.The American Society for Clinical Investigation,Inc,1989,83:637-46.
    25. Kilgore KS, Lucchesi BR. Reperfusion injury after myocardial infarction: the role of free radicals and the inflammatory response[ J ]. Clin Biochem, 1993, 26 (5) : 359.
    26.申文祥,党瑜华,陈魁等.冠状动脉粥样硬化性心脏病患者血浆可溶性细胞间粘附分子-1和可溶性血管细胞粘附分子-1水平检测.郑州大学学报(医学版),2007,42:546-8.
    27. Burns SA , DeGuzma BJ , Newburger JW et al. P-selectin expression in myocardium of children undergoing cardiopulmonary bypass. J Thorac Cardiovasc Surg, 1995, 110: 924
    28. Smith CW , Entman ML , Lano CL et al. Adherences of neutropils to canine myocytes in vitro is dependent on ICAM -1. J Clin Invest, 1991, 88: 1216
    29. Smith CW , Marlin SD, Rothlein R et al. Cooperative interactions of LFA-1 and Mac-1 with ICAM -1 in facilitating adherence and transendothelial migration of human neutrophils in vitro. J ClinInvest, 1989, 83: 2008.
    30.范慧敏,李伦明,张凯伦等.体外循环时心肌细胞上ICAM-1的变化及抑肽酶对其表达的影响.同济医科大学学报,2001,30:240-51.
    31. Hall R I, Smith M S, Rocjer G .The systemic inflammatory response to cardiopulmonary bypass: pathophysiological ,therapeutic, and pharmacological considerations. Anesth Analog,1997, 85: 7667~82.
    32. Wan S, Lecher JL , V incent JL . Inflammatory response to cardiopulmonary bypass: mechanisms involved and possible therapeuticst rategies. Chest, 1997, 112: 676~92.
    33.覃建明.乌司他丁的药理作用及临床应用进展.中国医药导报.2008,4(5):19-20.
    34.蓝瑞琼,蒋亚斌.国产乌司他丁治疗急性胰腺炎的系统评价[J].中华消化杂志,2005, 25( 10) : 618- 619.
    35.何俊峰,山峰.乌司他丁的临床应用进展.山东医药,2007,47:118-9.
    36. Fries E , Blom AM.Bikunin-not just a plasma proteinase inhibitor[ J ]. Int J Biochem Cell Biol, 2000, 32 (2) : 125-37.
    37. Formela LJ, Galloway SW, Kingsnorth AN, et al. Inflammatory mediators in acute pancreatitis[J].Br J Surg, 1995, 82(3): 613- 7.
    38.仲吉英,杨承祥,肖平.乌司他丁在体外循环心脏手术中对细胞免疫功能的影响[J].第四军医大学学报, 2007,28(1): 51- 3.
    39.向强,杨小文,董爱萍,等.乌司他丁对成人先天性心脏病手术炎性反应的影响[J].中国体外循环杂志, 2007, 5( 1) : 17- 9.
    40. Damas P, Canivet JL, de Groote D, et al . Sepsis and serum cytokine concentrations[J]. Crit Care Med, 1997, 25: 405-12.
    1.范玲玲,侯明星,龚玉华.乌司他丁的药理作用及临床应用进展.内蒙古医学杂志.2007,39:63-5.
    2.覃建明.乌司他丁的药理作用及临床应用进展.中国医药导报.2008,4(5):19-20.
    3.蓝瑞琼,蒋亚斌.国产乌司他丁治疗急性胰腺炎的系统评价[J].中华消化杂志,2005, 25( 10) : 618- 619.
    4. Kato Y, Kudo M, Sh inkawa T, et al . Role of O-linked carbohydrate of human urinary trypsin inhibitor on its lyso somalmembrane stabilizing property[ J ]. Biochem Biophys Res Commun, 1998, 243( 2) :377-383.
    5. Formela LJ, Galloway SW, Kingsnorth AN, et al. Inflammatory mediators in acute pancreatitis[J].Br J Surg, 1995, 82(3): 613- 7.
    6. Fries E , Blom AM.Bikunin-not just a plasma proteinase inhibitor[ J ]. Int J Biochem Cell Biol, 2000, 32 (2) : 125-37.
    7.潘成,虞惠康,罗月娥.注射用乌司他丁[J ].中国新药杂志,2000 ,9 (2) :123.
    8.大西治夫.Ulinastatin[J ].Biomedical Sciences .1984,5 (2) :76.
    9.吴伟芳,方强,方雪玲.乌司他丁对脓毒症患者免疫功能的影响[J].中国急救医学,2006, 26( 11) : 872- 4.
    10.胜利,安利峰,史霖,等.乌司他丁抗衰老的免疫机制[J].武汉大学学报(医学版),2006, 27( 5) : 597- 600.
    11.张延伟.乌司他丁的药理作用及临床应用进展.中国药房,2007 ,8(35):2788-9.
    12.旷昕,黄艳.乌司他丁对体外循环心脏病人血浆TNF-α, IL-6和IL-8的影响[J ].中国医学工程,2004,12 (5) :261.
    13.李伟,王剑,蒋艳波,等.乌司他丁对术中单肺通气患者白介素- 8的影响[J ].癌症,2003 ,22 (10) :174.
    14.仲吉英,杨承祥,肖平.乌司他丁在体外循环心脏手术中对细胞免疫功能的影响[J].第四军医大学学报, 2007,28(1): 51- 3.
    15.向强,杨小文,董爱萍,等.乌司他丁对成人先天性心脏病手术炎性反应的影响[J].中国体外循环杂志, 2007, 5( 1) : 17- 9.
    16.任同悦,杨晓伟,马越,等.乌司他丁在体外循环心内直视手术期间对心肌再灌注损伤的保护作用.中华医学杂志,2003,8(3):25.
    17.杨建胜,陈良万,邱罕凡.乌司他丁在婴幼儿体外循环手术期间的心肌保护作用.中国心血管病研究杂志,2006,8(4):595-7.
    18.陈萍,章晓华,陈伟达,等.乌司他丁在体外循环心脏手术中对心肌的保护作用.广东医学,2003,24:481-3.
    19.丁金贵,周广利,孟冬梅,等.乌司他丁对心脏直视手术患者围体外循环期炎性细胞因子和自由基的影响.中华麻醉学杂志,2001,21:724.
    20. Kawai T,Wada Y,Nishiyama K,et al. Usefulness of ulinastatin as a radical scavenger for protection of reperfusion injury after myocardial ischemia in o pen heart surgery. Nippon Kyobu GekaGakkai Zasshi,1991,39:2157- 2162.
    21. Watanabe A, Sumita S , Ichimiya T , et al. Effects of ulinastatin on extravascular lung water volume in patients under going cardiopulmonarybypass[J ].Masui,1994 ,43 (1) :78.
    22. Kawamura T , lnadaK , Kimura O , et al.The inhibitory effects of ulinastatin on the increase of IL - 8 and IL - 6 during heart surgery[J ].Masui ,1994 ,43 (12) :1818.
    23. Sugita T,Watarida S, Katsuyama K, et al. Effect of a human urinary protease inhibitor(Ulinastatin) on respiratory function in pediatric patients undergoing cardiopulmonary bypass[ J] . J Cardiovasc Surg, 2002, 43: 437- 440.
    24.徐康清,孙培吾,黄文起,等.乌司他丁对体外循环心脏手术后肺功能的影响[ J] .中华胸心血管外科杂志,2004, 20: 7- 9
    25. Ueki M,Yokono S,Nogaya J,et al.Effects of ulinastatin on postoperative renal function after cardiopulmonary bypass[J]. Masui,1995,44 (5):691-7.
    26.何小京,常业恬,陈爱武等.乌司他丁对体外循环心脏手术后病人肾功能的影响.中华麻醉学杂志,2004,3(24):28-9.
    27.李国强,王学浩,孙倍成.乌司他丁对肝切除患者围手术期免疫功能的影响[J].中华肝胆外科杂志,2002,8 (1) :50.
    28.王军,李水清,蒋建渝.乌司他丁应用于脊柱内固定手术围手术期对围术期免疫功能和肾功能的影响[J ].中国临床药理学杂志,2002 ,18 (3) :174.
    29.李立,田大广,李晓延,等.腹部大手术后运用乌司他丁减少手术侵袭的临床观察[J].中华肝胆外科杂志,2001 ,7 (5) :315.
    30.余剑波,姚尚龙.乌司他丁对围手术期控制性低血压患者影响的临床研究[J].中国急救医学, 2007, 27( 1) : 30-3.
    31. Ohnishi H, Suzuki K, Niho T, et al. Protective effects of urinary trypsisinhibit or inex- perimental shock[ J ]. Jpn J Phar macol, 1985, 39(2) : 137-44.
    32.林晃纪,种田,益造,等.乌司他丁对失血所致低血压患者的临床作用研究[J].急救医学(日) , 1988, 12: 187-92.
    33.丁梯杰,林德谦,曾云记.乌司他丁对创伤性休克患者手术后肾功能的影响[J].现代中西医结合杂志, 2007, 16(14): 1914- 1915.
    34.陈聪聪,柳子明,王慧华,等.乌司他丁对大鼠肾缺血/再灌注损伤的保护作用[J].中华麻醉学杂志, 2004, 24 ( 11 ) : 828-32.
    35.潘成,虞惠康,罗月娥.注射用乌司他丁[J ].中国新药杂志,2000 ,9 (2) :123.
    36.沈锦松,万莉萍,沈震.乌司他丁对严重创伤患者凝血功能的影响[J].中华急诊医学杂志, 2006, 15( 7) : 650- 652.
    37. Shimazaki E, Tanaka H, Ohta S, et al. Effects of the anti proteaseulinastatin on mortality and oxidant injury in scalded rats[J]. A rch Surg, 1995, 130 (9) : 994-7.
    38.程海波,唐会杰,张涛,等.乌司他丁对大面积烧伤休克期治疗的临床研究[J].中国基层医药, 2006, 13( 8) : 1330-1.
    39. Mccuskey RS, Urbaschek R, Urbaschek B, et al. The microcirculation during endotoxemia [J]. Cardiovescular Res, 1996, 32 (4):752-63.
    40.尹勇,高乃荣,李兆丽.乌司他丁对急性坏死性胰腺炎大鼠肺损伤的保护作用[J].世界华人消化杂志,2002 ,10 (5) :558.
    41.吴稚莉,海燕,田炳章.乌司他丁对急性坏死性胰腺炎模型大鼠血清淀粉酶、肿瘤坏死因子的影响[J].中国药房,2004 ,15(9) :535.
    42.上海乌司他丁临床试验协作组.国产乌司他丁治疗急性胰腺炎的多中心临床研究[J].中华消化杂志,2001 ,21 (5) :293.
    43.杨振林,郑树森,朱峰,等.两种不同途径应用乌司他丁治疗重症急性胰腺炎的疗效观察[ J ].中华肝胆外科杂志, 2005, 11(2) : 101-3.
    44. Hiyama A , Takeda J, Kotake Y, et al. A human urinary protease inhibitor (ulinastatin) inhibits neurrophil extracellular release of elastase during cardiopulmonary bypass [J].Cardiothorac Vasc Anesth ,1997,11:580.
    45. Damas P, Canivet JL, de Groote D, et al . Sepsis and serum cytokine concentrations[J]. Crit Care Med, 1997, 25: 405-12.
    46.卢燕,袁家瑜,郎冰.乌司他丁治疗全身炎症反应综合征疗效观察[J].宁夏医学院学报, 2006, 28( 6) : 550-2.
    47.陈海东,卓越.乌司他丁治疗急性肺损伤疗效观察[J].临床肺科杂志,2006, 11( 2) : 252- 3.
    48.曾文红,等.乌司他丁研究进展.中华肝胆外科,2001 ,7 (1) :53.
    49. Kondo D , Imaizumi M ,Abe T.Study on extravascular lung water and polymorphonuclear leukocyte elastase during acute phase following radical treatment of lung cancer:effect of ulinastatin on respiratory functions[J ] . Kyobu Geka ,1993 ,46 (11) :922.
    50.王勇,秦开秀.乌司他丁对急性肺损伤小鼠肺组织中白细胞介素-10表达的影响[J].中国药业, 2007, 16( 9) : 10-1.
    51.郭亮,张端莲,吴惠芬,等.乌司他丁对急性肺损伤组织中水通道蛋白表达的研究[J].数理医药学杂志, 2007, 20( 4):458-60.

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