HB-H-7树脂血液灌流吸附犬内毒素血症的实验研究
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:探讨应用HB-H-7树脂行血液灌流吸附治疗犬内毒素血症的有效性和安全性。
     方法:将12只成年杂种犬随机分为治疗组与对照组,每组6只,内毒素血症犬动物模型采用经中心静脉微量输液泵匀速输注内毒素0.5mg/kg, HB-H-7树脂经过工程制备和高压灭菌处理,灌流方式采用全血灌流,连续灌流2h。分别于灌流开始前、灌流开始后30分钟、60分钟和120分钟采集全血标本测定血浆内毒素、血浆蛋白、电解质和白细胞、红细胞及血小板。
     结果:血液灌流吸附前后比较,治疗组血浆内毒素水平明显下降(P<0.05),对照组无明显下降(P>0.05);两组比较差异有显著性(P<0.05)。HB-H-7树脂对血浆蛋白有一定影响,治疗组灌流吸附结束时与灌流吸附前比较,血浆总蛋白下降25.9%,白蛋白下降18.2%,球蛋白下降34.2%,统计学差异有显著性(P<0.05)。HB-H-7树脂对白细胞、红细胞、血小板及电解质没有明显影响(P>0.05)。治疗组犬实验后均长期健康存活,对照组犬于实验结束后14-22h全部死亡。
     结论:HB-H-7树脂列内毒素吸附率高,HB-H-7树脂血液灌流治疗犬内毒素血症安全有效。
OBJECTIVE:Discuss the effectiveness and safety of treating the endotoxemia dog model with hemoperfusion application of HB-H-7 resin.
     METHODS:12 dogs were divided randomly into treatment and control groups, 6 dogs in each group. Endotoxemia of model dogs was performed by infusing endotoxin 0.5 mg/kg through central venous using micro-infusion pump. HB-H-7 resin, which was prepared by projective preparation and high-pressure sterilization, perfused for 2h through whole blood hemoperfusion.
     RESULT:The plasma endotoxin levels of treatment group were significantly decreased (p<0.05) after hemoperfusion, otherwise, there was no significant decline in the control group (p>0.05), so there were significant difference (P<0.05) between the two groups. Plasma protein was affected by HB-H-7 resin in some degree. Total plasma protein declined 25.9% after perfusion, in which plasma albumin fell 18.2%, and globulin 34.2%, there was significant difference(p<0.05) in statistics. There was no apparent impact on the red blood cells, platelets and electrolyte. All of the model dogs in treatment group survived healthy for a long time after experiment, but all of that in the control group were died after 14-22 h.
     CONCLUSION:Endotoxin can be highly absorpted by HB-H-7 resin, so it is safe and effective to treat endotoxemia dogs animal model with HB-H-7 resin through hemoperfusion.
引文
[1]Cohen J. The dectection and interpretation of endotoxemia[J]. Inten Care Med 2000,26:S51-S56.
    [2]Taniguchi T, Hirai F, Takemoto Y, et al. A novel adsorbent of circulating bacterial toxins and cytokines:the efect of direct hemoperfusion with CTR column for the treatment of experimental endotoxemia[J]. Crit Care Med,2006,34(3): 800-806.
    [3]Taniguchi T, Kurita A, Mukawa C, et al. Dose-related effects of direct hemoper-fusion using a cytokine adsorbent column for the treatment of experimental endo-toxemia[J]. Intensive Care Med,2007,33(3):529-533.
    [4]徐修礼,于文彬.内毒素血症的实验诊断方法学进展[J].国外医学临床生物化学与检验学分册,2000,21(4):204-205.
    [5]O'ReIlly M, Newcomb DE, Remick D, et al. Endotoxin, sepsis, and the primrose path[J]. Shock,1999:12(6):411-416.
    [6]Karima R. The molecular pathogenesis of endotoxic shock and organ failure[J]. Mol. Med Today,1999; 5:123-125.
    [7]Wolf S M. Monolonal antibodies and the treatment of gram-negative bacteremia and shock[J]. N Eng J Med.1991; 324(7):486-489.
    [8]赵龙风,韩德五.肝病患者内毒索血症的临床意义.世界华人消化杂志,1999.5:391—393.
    [9]Camerer E, Cornelissen I, Kataoka H, et al. Roles of protease-activated receptors in a mouse model of endotoxemia[J]. Blood,2006:107(10):3912-3921.
    [10]唐虹.内毒素及内毒素血症治疗研究进展[J].医学综述,2005,11(2):109-111.
    [11]Sakamoto W, Nishihira J, Fujie K, et al. J Nutr Sci Vitaminol(Tokyo),2000, 46(6):316-319.
    [12]蒋力生,陈鹏.脓毒症与内毒素血症的治疗现状与展望[J].中国普外基础与临床杂志,2004,11(6):551-553.
    [13]赵洁,贾建伟.内毒素血症的治疗进展[J].医学综述,2006,12(1):49-51.
    [14]王顺宾.抗生素诱导革兰阴性杆菌释放内毒素的研究进展[J].国外医药抗 生素分册,1998,19(5):342-343.
    [15]Ekremoglu M, Turkozkan N, Erdamar H, et al. Protective effete of taurine on respiratory burnt activity of polymorphonu clear leukocytes in endotoxemia [J]. Amino Acids,2007:32(3):413-417.
    [16]Taniguchi T, Kurita A, Mukawa C, et al. Dose-related effects of direct hemo-perfusion using a cytokine adsorbent column for the treatment of experimental endotoxemia[J]. Intensive Care Med 2007:33(3):529-533.
    [17]Yan YJ, Li Y, Lou B, et al. Beneficial efects of ApoA-I on LPS-induced acute lung injury and endotoxemia in mice [J]. Life Sci,2006,79(2):210-215.
    [18]麻莉,刘友生.抗内毒素治疗的研究现状[J].中华烧伤杂志,2003,19(3):190-192.
    [19]张永辉.肝硬化内毒素血症的发生机制及治疗进展[J].浙江中西医结合杂志,2007,17(8):528-529.
    [20]王文江.中医药抗内毒素血症治疗的研究进展[J].中国中西医结合急救杂志,2004,11(5):317—320.
    [21]毛军,黄莉.肝病肠源性内毒素血症研究现状[J].中华实用中西医杂志,2003,3(16):1049-1050.
    [22]郭力,董南丁,熊爱民等.四君子汤加味防止烫伤后大鼠肠道损伤和细菌易位实验研究[J].中华烧伤杂志,2003,19:89-91.
    [23]王进,刘德宏.参附注射液对内毒素所致大鼠全身炎症反应综合征的作用[J].中国中西医结合急救杂志,2006,35(4):353-356.
    [24]Tsuda K. Taniguchi T. Effects of extracorporeal treatment with Lixelle on the mortality an d inflammatory responses to endotoxin-induced shock in rats[J]. Ther Apher Dial,2006,10(1):49-53.
    [25]臧雷.利用人血浆高密度脂蛋白治疗内毒素血症.中国新医药,2004,3(4):62-64.
    [26]段钟平.血液灌流吸附与人工肝脏支持.中华肝脏病杂志,2003,11(8):503-505.
    [27]Fu Guoqi, Chen Xinfu. Preparation of a new adsorbent for removal of low density lipoprotein[J]. Chemical Journal of Chinese Universities,2004,25 (6): 1183-1185.
    [28]Fang Hui, Wei Jiao, Yu Yaoting. Studies on adsorption performance of affinity adsorbent for bacterial endotoxins[J].Chemical Journal of Chinese Universities, 2004,25 (6):1056-1059.
    [29]Chang T M S. Can J Physiol Pharm,1969,47:1043-1050.
    [30]雷海波,高保娇.血液灌流用高分子吸附材料的研究进展[J].中北大学学报,2007,28(3):241-245.
    [31]王慧彦,侯光辉,袁直.以壳聚糖为载体的内毒素吸附剂[J].高等学校化学学报,2005,26(4):680-682.
    [32]张建达,袁直.血液灌流材料研究进展[J].高分子通报,2004,4:23-28.
    [33]马育.血液净化吸附剂研究进展[J].中国血液净化,2006,5(11):783-785.
    [1]徐修礼,于文彬.内毒素血症的实验诊断方法学进展[J].国外医学临床生物化学与检验学分册,2000,21(4):204-205.
    [2]赵龙凤,韩德五.肝病患者内毒素血症的临床意义[J].世界华人消化杂志,1999,05.15;7(5):391-395.
    [3]李晓燕,吕文哲,黄小正.中西医治疗肝病肠源性内毒素血症的研究进展[J].中西医结合肝病杂志,2002,12(5):316-320.
    [4]魏曦.正常菌群与健康[M].上海科技出版社.1985.
    [5]赵海英,王惠吉,等.肝硬化患者肠道菌群的研究[J].中华消化杂志,2003,23(7):407-409.
    [6]姚国相,沈忠文.门静脉高压症时细菌易位与内毒素血症和一氧化氮之间关系的实验研究[J].中华普通外科杂志,2001,7(16):379-381.
    [7]黄自平.肠源性内毒素血症在肝硬化失代偿中的作用及其处理[J].胃肠病学和肝病学杂志,1997,6(1):9-11.
    [8]邵祥稳.慢性肝病患者血浆内毒素和细胞因子变化研究与微生态制剂的干预[J].中国现代医学杂志,2003,13(22):83-85.
    [9]黄自平.肠源性内毒素血症在肝硬化失代偿中的作用及其处理[J].胃肠病学和肝病学杂志,1997,6(1):9-24.
    [10]中村东树他.肝病洞壁细胞研究的进展[M].东京:国际医书出版.1990.248.
    [11]Fox ES, Thomas P, Bmitman SA. The macrophage 80 Kda endotoxin binding protein is not present on rat kupffer cells[J]. Gastroenterology,1990,98:586.
    [12]Sakamoto W, Nishihira J, Fujie K, et al[J]. J Nutr Sci Vitaminol(Tokyo), 2000 Dec,46(6):316-322.
    [13]韩德五.肝功能衰竭发病机制的研究-肠源性内毒素血症假说[J].肝脏病杂志,1995.3(3):134-137.
    [14]韩德五.赵龙风.肠源性内毒素血症在肝炎慢性化中的作用[J].基础医学与临床.1999.19(6):482-486
    [15]赵汝饮.肝病时的肠源性内毒素血症[J].中国综合临床,1999.15(6):500.
    [16]Fink MP. Ethyl pyruvate:a novel treatment for sepsis[J]. Curt Drug Targets 2007,8(4):515-518.
    [17]Sharma R, Tepas JJ 3rd, Hudak ML, et al. Neonatal gut barrier and multiple organ failure:role of endotoxin and proinflammatory cytokines in sepsis and necrotizing enterocolitis[J]. J Pediatr Surg,2007,42(3):454-461.
    [18]Su CF, Yang FL, Chen HI. Inhibition of inducible nitric oxidesynthase attenuates acute endotoxin—induced lung injury in rats[J]. Clin Exp Pharmacol Physiol 2007,34(4):339-46.
    [19]朱戎,李菊兰,万苹,等.肠道菌群调整对肝硬化病人临床症状及实验室指针的观察[J].中国微生态学杂志,1999,11(1):43-46.
    [20]华静,李继法,曾民德,等.双歧三联活菌对肝硬化患者肠道菌群的调节作用及其对内毒素血症的影响[J].中华消化杂志,2000,20(2):136-138.
    [21]Sheng ZY, Yao YM, Yu Y. The relationship between gut derived endotoxemia and tumor necrosis factor. neopterin:experimental and clinical studies[J]. Chin Ivied,1997,110:30-35.
    [22]Creely SJ, McTernan PG, Kusminski CM, et al. Lipo polysaccharide activates an innate immune system response in human adipose tissue in obesity and type 2 diabetes[J]. Am J Physiol Endocrinol Metab,2007,292(3):E740-E747.
    [23]Schlag G, Lechner AJ, Heumann D, et al. Polymyxin B-immobilized fiber hemoperfusion with low priming volume in an elderly septic shock patient'vitIl marked endotoxemia[J]. ASAIO J,2005,51(4):482-484.
    [24]Carbonell LF, Diaz J, Hernandez I, et al. N-acetylcysteine execs protective efects and prevents lung redox imbalance and peroxynitrite generation in endotoxemic rats[J]. Med Chem,2007,3(1):29-34.
    [25]Taniguchi T, Kurita A, Mukawa C, et al. Dose-related effects of direct hemoperfusion using a cytokine adsorbent column for the treatment of experimental endotoxemia[J]. Intensive Care Med,2007,33(3):529-533.
    [26]赵世峰,沈洪.内毒素血症早期治疗的基础研究[J].世界急危重病医学杂志,2007,4(3):1884-1888.
    [27]Nielsen JS, Larsson A, Rix T, et al. The effect of activated protein C on plasma cytokine levels in a porcine model of acute endotoxemia[J]. Intensive Care Med 2007,25:174-177.
    [28]陆付耳,李鸣真,叶望云,等.论内毒素血症的治疗对策[J].中国危重病 急救医学,2000,12(10):579-582.
    [29]Thaveeratitham P, Khovidhunkit W, Patumraj S, et al. High density lipoproteins (HDL) inhibit endotoxin-induced leukocyte adhesion on endothelial cells in rats: effect of the acutephase HDL[J]. Clin Hemorheol Microcirc,2007,36(1):1-12.
    [30]Fukui H. Relation of endotoxin, endotoxin binding proteins and macrophages to severe alcoholic liver injury and multiple organ failure[J]. Alcohol Clin Exp Res 2005; 29 (11 Suppl):172S-179S.
    [31]梅爱敏,张淑慧.治疗肝病内毒素血症的进展[J].中国医院医药学杂志,2003,23(2):111-112.
    [32]Wang H, Li W, Goldstein R, et al. HMGB1 as a potential therapeutic target[J]. Novartis Found Symp,2007,280:73-75.
    [33]Sakamoto Y, Mashiko K, Matsumoto H, et al. Effect of direct hemoperfusion with a polymyxin B immobilized fiber column on high mobility group box-1 (HMGB-1)in severe septic shock:report of a case[J]. ASAIO J,2006,52(6): e37-e39.
    [34]Guha M, Mackman N. LPS induction of gene expression in human mono-cytes[J]. Cell Signal,2001,13(2):85-92
    [35]Tsuda K. Taniguchi T. Effects of extracorporeal treatment with Lixelle on the mortality an d inflammatory responses to endotoxin-induced shock in rats[J]. Ther Apher Dial,2006,10(1):49-53.
    [36]Taniguchi T, Hirai F, Takemoto Y, et al. A novel adsorbent of circulating bacterial toxins and cytokines:the efect of direct hemoperfusion with CTR column for the treatment of experimental endotoxemia[J]. Crit Care Med,2006, 34(3):800-806.
    [37]Taniguchi T, Kurita A, Mukawa C, et al. Dose-related effects of direct hemo perfusion using a cytokine adsorbent column for the treatment of experimental endotoxemia[J]. Intensive Care Med,2007,33(3):529-533.
    [38]Lehmann C, Meissner K, Knock A, et al. Activated protein C improves intestinal microcirculation in experimental endotoxaemia in the rat[J]. Crit Care,2006, 10(6):157-163.
    [39]汪承柏.重视慢性肝炎内毒索血症的防治[J].中西医结合肝病杂志,2001, 11(4):193-195.
    [40]毛军,黄莉.肝病肠源性内毒素血症研究现状[J].中华实用中西医杂志,2003,3(16):1049-1050.
    [41]王文江.中医药抗内毒素血症治疗的研究进展[J].中国中西医结合急救杂志,2004,11(5):317-320.
    [42]郭力,董南丁,熊爱民等.四君子汤加味防止烫伤后大鼠肠道损伤和细菌易位实验研究[J].中华烧伤杂志,2003,19:89-91.
    [43]骆抗先主编.乙型肝炎基础和临床[M].第1版.北京:人民卫生出版社,1997:481.