用户名: 密码: 验证码:
纳米党参合剂调整肠道微生态失衡防治多器官功能障碍综合症的研究
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:本实验研究了纳米党参合剂通过调整菌群失调,修复肠屏障功能,控制细菌、内毒素易位,对多器官功能障碍大鼠肠源性感染及内毒素血症(IETM)进行防治,减轻由IETM及其引起的细胞因子连锁反应造成对多器官功能障碍(MODS)的“二次打击”,达到改善相应症状,降低死亡率的目的。
     方法:选用Wistar大鼠70只,采用肠缺血再灌注的方法制造MODS的模型。分别以纳米中药、常态中药、丽珠肠乐对动物进行灌胃治疗,一周后处死动物。取肠内容物、肝、肺、脾、肠、肠系膜淋巴结,门静脉血,分别做无菌培养,病理学切片,CD4+、CD4+/CD8+计数,内毒素及SIgA的测定。
     结果:本实验成功的复制出多器官功能障碍的模型,模型建立组动物出现菌群失调,细菌易位,内毒素血症;同时伴有两个及两个以上脏器损伤;CD4+减少,CD4+/CD8+比值下降甚至出现比值倒置,SIgA水平明显下降。与正常对照组相比差异显著。各治疗组通过扶植肠道有益菌、抑制有害菌的生长繁殖并促进其排泄,保护肠黏膜屏障,明显降低了细菌易位,控制内毒素血症,改善了其他各相关病理、免疫指标。整体疗效,纳米中药、常态中药及丽珠肠乐均有效,但纳米中药在控制内毒素血症,提高免疫力等方面优于常态中药和丽珠肠乐,差异有统计学意义。
     结论:肠缺血再灌注造成的MODS伴有严重菌群失调,细菌、内毒素易位,是MODS发生、发展的重要因素。党参合剂从调整微生态失调的角度来防治MODS取得较好效果,纳米中药效果更佳。
Objective: We designed the experiment in order to study Nano- dangshen mixture prevent and cure intestinal infection and endotoxemia (IETM), by adjusting dysbacteriosis, repair intestinal barrier function, control bacteria and toxins translocation, in the Multiple Organ Dysfunction Syndrome (MODS).Abating“The Secondary Injury”to MODS, caused by IETM and cell factor chain reaction, to improve the corresponding symptom, and reduce mortality.
     Method: Selection of 70 Wistar rats, to prepared the rat model of MODS by intestinal ischemia- reperfusion. Intragastric administration with Nano Chinese medicine, Normal Chinese medicine and Bifidobiogen Livzon respectively.Then after one week the animals were killed to detected the changing of bacteria quantity and location, determination of plasma endo- toxin level, intestinal contents level of SIgA, CD4 +, CD8 + counting, and pathology examination.
     Results: This study to reproduced MODS model successfully, The model group had dysbacteriosis, bacterial and endotoxin translocation, at the same time with two and two or more organ damaged, CD4 + reduction, CD4 + / CD8 + ratio fell even inverted ratio, SIgA level decreased significantly. Compared with the normal group significantly. The therapy groups reduced bacterial and endotoxin translocation significantly, controlled IETM , improved relevance index of pathology and immunity, by regulating intestinal dysbacteriosis, and repairing intestine barrier function.The overall effect, Nano-CM, Normal-CM and Bifidobiogen Livzon were all effective, but Nano-CM was better than Normal-CM, and Bifidobiogen Livzon in the effect of controlling IETM and improving immunity, the difference was significant(p<0.05).
     Conclusion: The model group has serious dysbacteriosis, bacteria and toxins translocation which is the key factors of MODS occurrence and development. Dangshen mixture prevent MODS by regulating intestinal dysbacteriosis get fairly good effect, by comparing with Normal-CM, Nano-CM, we concluded that the later is more effevtive than the former .
引文
[1]李兰娟.感染微生态学[M].北京:人民卫生出版社,2002.
    [2]康白主编.微生态学原理[M].第1版.大连:大连出版社,1996:42~856.
    [3]康白.正常微生物群是一个新的人体生理学系统[J].中国微生态学杂志,2003,15(2):63~65.
    [4]康白译述.新抗微生物战略[M].大连:中国微生态学杂志编辑部,1997:2~44.
    [5]杨景云.医用微生态学[M].北京:中国医药科技出版社,1997.
    [6]蒋忠铭,康白.感染的微生态防治[J].中国微生态学杂志,1989,1(1):114~115.
    [7] Nieu wenhuijzenGAP,Deitch EA,Goris RJA.Infection,the gut and the developmen of the multiple organ dysfunction syndrome[J].Eur J Surg,1996,162:259~273.
    [8] Rowlands BJ,Sqong CV,Gardiner KR.The gastro intestinal tract as a barrier in sepsis [J].British Medical Bulletin,1999,55:196~211.
    [9]黎介寿.加强对肠屏障功能障碍的研究[J].中华医学杂志,1999,79:581~582.
    [10] Stone HH,et al, Candida Sepsis,Pathogenesis and Principles of treatment[J]. Ann Surg1974, 179:697.
    [11] Marshall JC, et al, The microbiology of multiple organ failure, the proximal gastrointestinal tract as an occult reserrovir of pathogens[J]. Arch Surg, 1988,123:309.
    [12] Baker JW, et al. Hemorrhagic shock induces bacterial translocation from the gut[J]. Ttauma 1988,28:896.
    [13] Wilcox, MH. Clarithromycin and risk of Clostridium difficile-Associated diarrhra:A review [J].Antimicrob Chemother,2001 ,47:358~359.
    [14] Kazantsev GB,Hecht DW,Raoretal.Plasmid labeling confirm sbacteria ltranslocation inpan creatitis [J].Am J Surg,1994,167:201~207.
    [15] Mason AD, McManus AT, Pruitt BA, Diagnosis and monitoring of Closteidium difficile infection with polymerase chain ction[J]. Arch Surg, 1986, 121(9):10~17.
    [16] Moore FA, Moore EE, Poggetti RS et al. Current European concepts in the management of Helicobatter pylori infention [J]. Arch Surg, 1992,127(8):893~897.
    [17] Sheng ZY, Don, YL, Wang XH. Tuberculous peritonitis: analysis of 35 cases [J].Chin Med [Engl], 1991,104(11):897~903.
    [18]谭新洪,黄震东.现代内科治疗学[M].广州:广东科学技术出版社,1997,68.
    [19] Murphy FJ. Targeting inflammatory diseases via apoptotic mechanisms[J]. Curr Opin Pharmacol,2003,3(4):41~42.
    [20]姚咏明,于燕,方文慧等。创伤后内毒素增敏效应在多器官损害中的作用[J]。中国危重病急救医学,1998,10(12):712~718.
    [21]金丽娟。细胞因子和创伤后多器官衰竭[J]。中国危重病急救医学,1995,7(6):33~35.
    [22] Welborn MB,Oldenburg HS,Hess PJ,et al.The relationship between visceral is chemia ,proinflammatory cytokines,and organ injury in patients under going thoracoab dominal aortic aneurysm repair[J].Crit Care Med,2000,28:3191~3196.
    [23] Adams JM,Hauser CJ,Adams CA Jr,et al.Entry of gut lymph into the Circulation primes rat neutrophil respiratory burst in hemorrhagic shock [J] .Crit Care Med,200l,29:2194~2199.
    [24] Le Tulzo Y. Early circulating lymphocyte apoptosis in human septic shock is associated with poor outcome[J].Shock,2002,18(6):48~51.
    [25] Renshaw M. Cutting edge:impaired toll-like receptor expression and function in aging[J].Immunol,2002,169(9):46~47.
    [26] Roger CB.Immunologic dissonance:a continuing evolution in our un-derstanding of the SIRS and MODS[J].Annals Internal Medicine,1996,128:680~684.
    [27] Beal AL,Cerra FB.Multiple organ failure syndrome in the1990's sys-temic inflammatory response and organ dysfunction[J].JAMA,1994,271:226~233.
    [28] Jeremitsky E. Harbingers of poor outcome the dayafter severe brain injury[J]. Trauma,2003,54(2):312~315.
    [29] Dellinger RP. Surviving sepsis campaign guidelines for management of septic shock[J]. Crit Care Med,2004,32(3):85~87.
    [30] Gando S. Combined activation of inflammation has an important role in MODS[J]. Thromb Haemost,2002,88(6):943~947.
    [31] Gando S,Nanaki S,Sasaki S,et al.Astivation of the extrinsic coagu-lation pathway in patients with severe sepsis and septic shock[J].N Engl J Med,1999,340:207~214.
    [32] Vervloet MG,Thijs LG,Hack CE.Derangements of coagulation and fibrinolysis in critically ill patients with sepsis and septic shock[J].Semin Thromb Hemost,1998,24:33~44.
    [33]何振扬,殷红梅,苏哲坦,等.创伤后血清NO浓度变化与TNF-α水平之间的相关性及其在创伤后MODS发病中的意义[J].中国急救医学,2003,23:504~505.
    [34]沈戈,江观玉.新世纪国内MODS防治研究的反思与展望[J].中国危重症急救医学,2001,13(9):520~522.
    [35]姚咏明,盛志勇.我国创伤脓毒症基础研究新进展[J].中华创伤杂志,2003,19(1):65~67.
    [36]任成山,刘绪钊,郭中杰,等.全身炎症反应综合征1292例临床分析[J].中华内科杂志,1999,38:40~43.
    [37] SwankGM,DeithEA.Role of the gut in multiple organ failure:Bacterial translocation and permeability changes [J].World J Surg,1996,20:411~417.
    [38] PastoresSM,KatzDP,KvetanV.Splan chnicis chemia and gut mucosal injury insepsis and the multiple organdys function syn-drome[J].Am J Gastroenterol,1996,91:1697~1710.
    [39] Bounous G, et al. Biosynthesis of mucin in shock Relation to tryptic hemorrhagic enteritis and Permeabbility to curare[J]. Ann surg 1966,164:13.
    [40] Chiu CJ,et al.Intestinal mucosal lesion in low flow states[J]. Arch Surg 1970,101:478.
    [41] Ding JW,Andersson R,Soltesz V,et al. The role of bile and bile acids in bacterial translocation in obstructive jaundice in rats[J].Eur Surg Res,1993,25(1):11.
    [42] SwankGM,DeithEA.Role of the gut in multiple organ failure:Bacterial translocation and permeability changes [J].World J Surg,1996,20:411~417.
    [43]李鸣真.肠道细菌和内毒素的易位[J].中国危重病急救医学,1998,10:764~767.
    [44] Nieu wenhuijzenGAP,Deitch EA,Goris RJA.Infection,the gut and the developmen of the multiple organ dysfunction syndrome[J].Eur J Surg,1996,162:259~273.
    [45]任添华.多器官功能障碍综合征与细胞凋亡[J].中国急救医学,2003,23:159~162.
    [46] Cobb JP,Hotchkiss RS,Karl IE,et al.Mechanisms cell injury and death.Br J Anaesth ,1996,77:3~10.
    [47] Hotchkiss RS,Swanson PE,Freeman BD,et al.Overexpression of Bcl-2in tranagenic mice decreases apoptosis and improves survival in sepsis.J Immunol, 1999, 162: 4148~4156.
    [48] Rosengart MR. Mitogen activated protein kinases in the intensive care unit[J]. Ann Surg,2003,237(1):94~99.
    [49]谢敏.136例严重急性呼吸综合征的临床特点分析[J].中国呼吸与危重监护杂志,2003,2(4):200~202.
    [50]单红卫,杨兴易,陈学云,等.失血性休克时大鼠全身氧供给与氧消耗关系变化的研究[J].中国普通外科杂志,2000,9:415~417.
    [51]赵良,陈学云,杨兴易等.严重感染病人的氧代谢动力学变化[J].中国急救医学,1998,18:4~6.
    [52]王正国.创伤与多器官衰竭[J].中国危重病急救医学,1995,7(6):335.
    [53]陈德昌.多器官功能障碍综合征与感染[J].中华医学杂志,1996,76:246~247.
    [54]林洪远,盛志勇.全身炎症反应和MODS认识的变化及现状[J].中国危重急救医学,2001,13(11):643~646.
    [55]李春盛,王佩燕.多脏器功能障碍综合征[J].中华急诊医学杂志,2001,10(1):68~69.
    [56]胡森.多器官功能障碍综合征研究的回顾与展望[J].中华烧杂志,2001,17(3):136~138.
    [57] Kollef MH .Seluester DP .The acute respiratory diatress syndrome[J] .N Engl . Med .1995,332:27~37.
    [58]John R. C. Dorinsky P. M .Immunologic therapy for ARDS, Septic shock and multipleor -gan failure[J].Chest,1993,103:932~43.
    [59]Liu M .Slutsky AS .Anti-inflammatory therapies application of molecular biolog-y techniqu-esin intensive care medicine[J].Intensive Care Med ,1997,22:718~31.
    [60]Hoffmann-H,Markewitz-A .Rreuzer-R .et al.Pentoxifvlline decreases the incidence of mult- iple organ failure in patients after major cardio-thoracic surgery [J].Shock ,1998,9:235~40.
    [61] Daniel G,Douglas R,Samuel J,et al.Combination immunotherapy with soluble tumour necrosis factor receptors plus interleukin-1recep-tor antagonist decreases sepsis mortality[J]. Crit Care Med,2001,29:473~481.
    [62] Manson WJ, Dijkema H, Klasen HJ.Use of propre and sunbiotics in the ICU-future options [J].Burns, 1996:16(2):166.
    [63] Mackie DP.Induction of a rat enteric defensin gene by hemorrhagic shock [J].Trauma., 1992, 32:1101.
    [64] Clark EC,Patel SD,Chadwick PR,etal.Glutam ined eprivation facilitates tumou rnecrosis factor induced bacterial translocation in Caco-2 cells by depletion of enterocyte fuel substrate [J] . Gut 2003, 52(2):224~230.
    [65]上海中医学院.中医年鉴(1983).第1版.北京:人民卫生出版社,1984,141.
    [66]王今达.开展中西医结合治疗急性危重病的思路和方法[J].中国中西医结合急救杂志,2000,7(6):323~325.
    [67]王今达,崔乃杰,高天元等.“菌毒并治”新理论临床应用价值和验证——“菌毒并治”治疗感染性多系统脏器衰竭50例的疗效观察[J].中国危重病急救医学,1989, 1(创刊号):17~20.
    [68]王今达,雪琳.细菌、内毒素、炎症介质并治——治疗重度脓毒症的新对策[J].中国危重病急救医学,1998,10(6):323~326.
    [69]陆付耳,李鸣真,叶望云.论内毒素血症的防治对策[J].中国危重病急救医学,2000,12(10):579~582.
    [70]陈德昌,景炳文,杨兴易等.大黄对胃肠功能衰竭的治疗作用[J].解放军医学杂志, 1996,21(1):24~26.
    [71]曲爱君,吴铁军,刘桂清,等.大黄对SIRS和MODS患者肿瘤坏死因子-α及白介素的影响[J].中国中西医结合急救杂志,2000,7(1):43~45.
    [72]王宝恩,张淑文,赵淑颖,等.重症感染并发MOF的诊治及其病理生理基础[J].中国危重病急救医学,1992,4(1):3~5.
    [73]陈海龙,吴咸中,关凤林,等.中医通里攻下法对多器官功能不全综合征时肠道屏障功能保护作用的实验研究[J].中国中西医结合杂志2000,20(2):120~122.
    [74]黄兴兰等.大黄对Bal b/c小鼠肠黏膜屏障保护作用的机理探讨[J].四川医学,1999, 20(5):486~487.
    [75]吴承堂等.急性坏死性胰腺炎犬肠道菌群的变化[J].中国普外基础与临床杂志,1999, 6(3):133~135.
    [76]陈军.烧伤血清对肠上皮细胞屏障功能损伤的实验研究[J].中华创伤杂志,2002, 18(5):301~304.
    [77]康焰.不同抗生素在G-细菌感染中诱导内毒素释放的研究[J].中国普外基础与临床杂志,2002,9(1):15~18.
    [78]张仁岭.四君子汤加大黄对脓毒症大鼠肠黏膜屏障功能的保护作用[J].中国中西医结合消化杂志,2006,14(3):160~163.
    [79]陈德昌,杨兴易,景炳文,等.大黄对多器官功能障碍综合征治疗作用的临床研究[J].中国中西医结合急救杂志2002,9(1):6~8.
    [80]陈德昌,杨兴易,景炳文等.大黄对危重症患者应激性胃肠粘膜病变的治疗作用及其机制的研究[J].中国危重病急救医学,1996,8(7):395~398.
    [81]陈德昌,景炳文.大黄对肠源性感染治疗作用的实验研究[J].中国急救医学,1993, 13(5):79.
    [82]阎勇,田伏洲,尹致良.丹参对肠道屏障的保护作用机制研究[J].中华消化杂志2000,20(6):409~411.
    [83]杨祥良.基于纳米技术中的中药基础问题研究[J].中国药科大学学报,2002,20(11):37~39.
    [84]高海明.纳米级粒径超微化通用装置[J].国外科技动态,1997,(10):47.
    [85]杨景云等.抗结核散对实验性脾虚小鼠肠道菌群以及免疫机能的影响[J].中国微生态学杂志,1993,5(1):18.
    [86]徐慧碧.雄黄抑制小鼠肉瘤S180的尺寸效应的初步探讨[J].武汉大学学报(自然科学版),2000,288~289.
    [87]余建新,韩春茂.益生菌的作用机制及临床应用前景[J].中国微生态学杂志,2002,14(6),371~372.
    [88]严梅祯等.四君子汤对实验性脾虚小鼠肠道菌群的影响[J].中国微生态学杂志1989,1(1):40.
    [89]杨景云等.扶正固本丸对小鼠肠道正常菌群的影响[J].中国微生态学杂志,1993,5(1):18.
    [90]杨景云等.中药扶正口服液对肠道菌群影响的研究[J].中国微生态学杂志,1999,19(3):32~33.
    [91]李丽秋等.树舌中药复方煎剂对小鼠肠道菌群以及体液免疫的调节作用[J].中国微生态学杂志,1997,9(6):24.
    [92]马淑霞等.扶正固本丸对肺结核患者肠道菌群的影响[J].中国微生态学志,1996,8(2):11.
    [93]杨景云.中医药微生态学研究进展.中国微生态学杂志,2007,15(2):1~3.
    [94]高玲鹃.纳米锁阳对实验大鼠肝性脑病肠道菌群及免疫功能调整的研究.2004硕士毕业论文.
    [95]鞠宝玲.纳米中药01对抗生素小鼠肠道微生态失调的调整作用.2003年硕士毕业论文.
    [96]康白,蒋寒青.微生态调节剂及其研究进展[J].中国实用儿科杂志1996,11(4):205~206.
    [97]魏曦,康白.正常菌群与健康[M].上海:上海科技出版社,1995.
    [98]康白云主编.双歧杆菌[M].大连:大连海大学出版社,1997.
    [99]李兰娟.肝功能衰竭开发感染与肠道细菌易位[J].中国微生态学杂志2001, 13(2):63~65.
    [100]罗海波,李兰娟,主编.细菌毒素与临床[M].北京:人民卫生出版社,1999,178~201.
    [101]杜淑旭,黄志华.妈咪爱对实验性黄疸家兔肠道菌群及胆红素代谢的影响[J].中国微生态学杂志,2001,13(5):271~274.
    [102]张东绅.医用微生态调节剂现状与展望[J].中国微生态学杂志,2002,14(4):4.
    [103] Rahman SH, Ammori BJ, Holmfield J, et al. Intestinal hypoperfusion contributes to gut barrier failure in severe acute pancreatitis[J].JGastrointest Surg 2003,7(1):26~35.
    [104] Moore FA, Moore EE, Jones TN. Intestinal tuberculosis [J]. Trauma,1989, 29(7):916~923.
    [105] Rowlands BJ, Sqong CV, Gardiner KR. The gastrointestinal tract as a barrier in sepsis [J] British Medical Bulletin,1999,55:196~211.
    [106] Zapata-Sirvent RL.Baterial translocation and permeability changes [J]. Surgery, 1993, 113(5):664.
    [107] Gianotti L, Alexander JW, Fukushima R et al.Baterial and fungal infection in acute liver failure [J].Am J Surg, 1993,165(I):196~200.
    [108] Huang KE, Chung DH, Heradon DN. Gastroenterology and Hepatology[J].Arch Surg. 1993,128(1):47~53.
    [109] Huang Y, Wang SR,YiC,etal. Effects of recombinant human growth hormone on rat septic shock with intraabdominal infection by E.coli[J].World J Gastroenterol 2002 ,8(6):1134~1137.
    [110] Wen LM , ZhangZ , ChenXJ.Neurotensin and intestine function [J]. World Chin J Digestol , 2001,9(7): 817.
    [111] MoriguchiT, HirasawaH, OdaS, etal. A patient with severe acute pancreat it is success fully treated with a new critical care procedure[J].The rApher 2002,6(3):221~224.
    [112]陈海龙,裴德凯,吴咸中等.肠道屏障在多器官功能不全综合征中的发病学意义研究[J].中华普通外科杂志,1998,13(1):50.
    [113]盛志勇,胡森.多器官功能障碍综合征[M].北京:科学出版社,1999,187~190.
    [114]全竹富,黎介寿.腹腔感染致多器官衰竭的动物模型[J].中华实验外科杂志,1991,8(2):91.
    [115]陈海龙,关凤林,吴咸中等.非细菌性多器官功能不全综合征的动物模型[J].中国急救医学,1997,17(2):1.
    [116]盛志勇,徐世豪,施志国等.肿瘤坏死因子致伤无菌大鼠多器官功能损害的初步研究[J].解放军医学杂志,1992,17(2):168.
    [117]陈海龙,裴德凯等.多器官功能不全综合症时肠道细菌微生态学改变的实验研究[J].中国微生态学杂志,1999,11(1):22~24.
    [118] DiebelLN, LiberatiDM, BrownWJ et al.Secretory immunoglobulinA blocks hypoxiaaugmented bacterial passage across Madin Darbycanine kindey cell monolayers [J] .Trauma 1997:43(5) :759~763.
    [119] DeitchEA,XuDaZhong,LuQi,et al.Elemengtal diet induced immune supper-ssion is caused by both bacteria and dietary factors[J].JPEN.1993,17(4):332~336.
    [120] HaskelY XuDaZhong,LuQi,et al. Elemengtal diet induced bacterial traslocation can be hormonally modulate[J]. Annsurg,1993,217(5):634~643.
    [121]吴恺,王冰娴,王兴鹏.谷氨酰胺对急性坏死性大鼠肠道黏膜局部免疫功能的保护作用[J].胃肠病学和肝病学杂志.10(1)2001,3:39~41.
    [122] AlverdyJC.effects of gultamine-supplemented diets on immunology of the gut [J] .JPEN,1990,14(4):109.
    [123]张仁岭等.四君子汤加味大黄对脓毒症大鼠肠黏膜屏障功能的保护作用[J].中国中西医结合消化杂志,2006,14(6):160~163.
    [124]张立德等主编.纳米材料和纳米结构[M].北京:科学出版社,2001.

© 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