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通腑汤对腹腔间隔室综合征肠黏膜屏障的干预作用
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摘要
1研究背景和目的肠道不仅是一个吸收和消化的器官,同时在机体非特异性抗感染防御系统中起着重要作用。完整的肠黏膜屏障功能是肠道多种功能得以正常维持的基础。在创伤和感染等应激情况下,肠道的屏障功能受到削弱或损害,就可使大量细菌和内毒素经由门静脉和淋巴系统侵入体循环,造成肠源性感染(Gut origin sepsis)和内毒素血症(Endotoxemia,ETM),并在一定条件下激发细胞因子和其他炎性介质的连锁反应,引起全身各器官的损害。因此,胃肠道被认为是导致多器官功能障碍综合征(multiple organs dysfunction syndrome, MODS)的“动力部位”和靶器官。腹腔间隔室综合征(abdominal compartment syndrome, ACS)时腹腔压增高,肠系膜动脉、肝动脉、小肠黏膜、肝脏微循环及门静脉血流减少,造成肠黏膜和黏膜下组织无氧代谢、酸中毒和缺血再灌注损伤,肠黏膜屏障功能受损,引起细菌和内毒素易位。因此研究腹腔压变化规律和腹内高压对肠黏膜屏障的影响,探讨腹腔间隔室综合征状态下肠黏膜屏障的防护措施等相关问题具有重要意义。
     通腑汤是导师李乃卿教授的经验方和北京中医药大学东直门医院院内制剂,临床应用已有30多年的历史。在治疗急性重症胰腺炎、胃大部切除术后肠蠕动迟缓、以及麻痹性肠梗阻等方面,能够改善患者腹胀、腹痛、促进肠鸣音恢复和排便排气。本研究在导师多年临床研究的基础上,采用现代中西医结合医学的研究方法,采用定量分析技术,对腹腔压变化的规律、腹腔压与血压变化的相关性、腹内对肠黏膜通透性的影响的病理生理改变进行初步探索;与谷氨酰胺相对照,研究了通腑汤对腹腔压的干预作用、对腹腔间隔室综合征肠黏膜通透性增高的干预作用、对肠系膜微循环的干预作用;并对消化道恶性肿瘤患者术后腹腔压变化以及通腑汤的临床疗效作了初步研究。
     2方法
     本课题从腹腔间隔室综合征发生的病理生理学基础、干预治疗和临床防治三个方面进行了一些研究。包括六个部分:第一部分,腹腔压变化规律的研究;第二部分,通腑汤对大鼠腹腔压变化的干预作用;第三部分,腹腔压变化对血压的影响;第四部分,通腑汤对腹腔间隔室综合征大鼠肠黏膜屏障功能的干预作用;第五部分,通腑汤对腹腔间隔室综合征大鼠肠系膜微循环的干预作用;第六部分,通腑汤对消化道肿瘤患者术后腹腔压变化的干预作用。
     第一部分,以SD大鼠为研究对象,以氮气气腹法成功制作了腹腔压增高的模型。定时定量向大鼠腹腔内注入氮气。利用MP-100A-CE型生理监护仪即时监测腹腔压动态变化。取每组各时间点腹腔压的算数平均值,绘制腹腔压和氮气量的散点图,应用回归分析方法分析腹腔压升高和降低的氮气量与腹腔压的函数关系。第二部分,腹腔高压造
1 Background and Objective
     Intestinal tract is not only an organ of absorptive and digestive, but also an important organ in the non-specificity anti-infection system. Integrity of gut barrier is the foundation of the multiple function of intestinal tract to keep normal. When gut barrier is injured in the trauma and infection, plenty of bacteria and endotoxin intrude into general circulation trough portal vein and lymphatic system, and induced gut origin sepsis and endotoxemia, which will stimulate cascade reaction of cytokines and mediators of inflammation,making multiple organ suffered. Thus intestinal tract is regarded as motive power of multiple organ dysfunction syndrome. Intra-abdominal pressure increases in abdominal compartment syndrome patients. Blood flow of mesenteric artery, hepatic artery, mucous membrane of small intestine, microcirculation of liver and portal vein decreases. Intestinal mucous membrane and submucous tissue anaerobic metabolism, acidosis and ischemical reperfusion injury are occurred. Gut barrier is injured and causing bacteria and endotoxin translocation. Therefore studying the variation regularity of intra-abdominal pressure, the effect of abdominal compartment syndrome on the gut barrier, and investigating the protective method of gut barrier are important.
     Tongfutang is an empirical formula of professor Li Naiqing and a preparation of Dongzimen Hospital of Beijing University of Chinese Medicine, which has been used for more than 30 years. In the treatment of acute sever pancreatitis, retardation of enterokinesia after subtotal gastrectomy and paralytic ileus, it can ameliorate abdominal distention, stomachache, promote bowel sound to recover,promote defecation and breaking wind. The investment based on professor Li’s long time clinical study of the preparation, adopting modern investment method of integrated Chinese and Western Medicine, using quantitative analysis technique, study the variation regularity of intra-abdominal pressure, the effect of intra-abdominal pressure on the blood pressure and intestinal mucosa permeability. Compared with glutamine, study the effect of Tongfutang on intra-abdominal pressure, the intervention in gut barrier dysfunction of abdominal compartment syndrome, and the influence on mesentery microcirculation. The effect of Tongfutang on intra-abdominal pressure of patients after alimentary tract malignant tumor surgery is observed clinically.
     2 methods
     The study investigate the pathologic physiology basis, treatment and clinical prevention
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    13. Hobson KG, Young KM, CirauloA, et al. Release of abdominal compartment syndrome improves survival in patients with burn injury. J Trauma,2002,53:1129-1133.
    14. Meldrum DR, Moore FA, Moore FF, et al. Prospective characterization and selective management of the abdominal compartment syndrome. Am J Surg, 1997,174:667-673
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    2. Flores-Alvarez E, Avila-Cuevas GE, de la Torre-Gonzalez JC, Early diagnosis and risk factors associated with abdominal compartment syndrome. Cir Cir. 2005 May-Jun; 73(3):179-83.
    3. Meldrum DR, Moore FA, Moore FF, et al. Prospective characterization and selective management of the abdominal compartment syndrome. Am J Surg, 1997,174:667-673
    4. Stagnitti F, Calderale SM, Priore F, et al. Ribaldi S,Abdominal compartment syndrome: patophysiologic and clinic remarks. G Chir. 2004 Oct;25(10):335-42.
    5. Wong K, Summerhays CF. Abdominal compartment syndrome: a new indication for operative intervention in severe acute pancreatitis. Int J Clin Pract. 2005 Dec;59(12):1479-81.
    6. Moore EE. Staged laparotomy for the hypothermia, acidosis and coagulopathy syndrome. Am J Surg, 1997, 174:667-673.
    7. Martinez-Ordaz JL, Cruz-Olivo PA, Chacon-Moya,et al. Management of the abdominal wall in sepsis. Comparison of two techniques. Rev Gastroenterol Mex. 2004 Apr-Jun;69(2):88-93.
    8. De Waele JJ, Hoste EA, Malbrain ML.Decompressive laparotomy for abdominal compartment syndrome - a critical analysis. Crit Care. 2006 Mar 27;10(2):R51 [Epub ahead of print]
    9. Kopelman T, Harris C, Miller R, et al. Abdominal compartment syndrome in patients with isolated extraperitoneal injuries[J]. J Trauma, 2000; 49(4):744
    10. Burrows R, Edington J, Robbs JV. A wolf in wolf’ s clothing: the abdominal compartment syndrome[J]. S Afr Med J,1995;85(1):46
    11. Oda J, Ueyama M, Yamashita K,et,al. Effects of escharotomy as abdominal decompression on cardiopulmonary function and visceral perfusion in abdominal compartment syndrome with burn patients. J Trauma. 2005 Aug;59(2):369-74.
    12. Chen RJ , Fang JF , Chen MF. Intra-abdominal pressure monitoring as a guideline in thenonoperative management of blunt hepatic trauma [J]. J Trauma, 2001; 51 (1): 44.
    13. Dakin GF, Nahouraii R, Gentileschi P, et,al. Subcutaneous endoscopic fasciotomy in a porcine model of abdominal compartment syndrome: a feasibility study. J Laparoendosc Adv Surg Tech A. 2004 Dec;14(6):339-44.
    14. Hinck D, Struve R, Gatzka F,et,al. Vacuum-Assisted Fascial Closure in the Management of Diffuse Peritonitis. Zentralbl Chir. 2006 Apr;131(S 1):108-110.
    15. Martinez-Ordaz JL, Cruz-Olivo PA, Chacon-Moya E, et,al. Management of the abdominal wall in sepsis. Comparison of two techniques. Rev Gastroenterol Mex. 2004 Apr-Jun;69(2):88-93.
    16. Letoublon C, Cardin N, Arvieux C. Laparostomy with vacuum pack technique. Ann Chir. 2005 Oct;130(9):587-9. Epub 2005 Sep 27.
    17. Kendrick JE 4th, Leath CA 3rd, Melton SM, et,al Use of a fascial prosthesis for management of abdominal compartment syndrome secondary to obstetric hemorrhage. Obstet Gynecol. 2006 Feb;107(2 Pt 2):493-6.
    18. Offner PJ, de Souza AL, Moore EE, et al. Avoidance of abdominal compartment syndrome in damage-control laparotomy after trauma [J].Arch Surg,2001;136(6):676.
    19. Saenko VF, Belianskii LS, Lisun IuB. Modern approaches to the problem of temporary closure of the abdominal cavity. Klin Khir. 2005 Mar;(3):5-11.
    20. Hultman CS, Pratt B, Cairns BA,et,al. Multidisciplinary approach to abdominal wall reconstruction after decompressive laparotomy for abdominal compartment syndrome. Ann Plast Surg. 2005 Mar;54(3):269-75; discussion 275.
    21. Hultman CS, Pratt B, Cairns BA, et al. Multidisciplinary Approach to Abdominal Wall Reconstruction After Decompressive Laparotomy for Abdominal Compartment Syndrome. Ann Plast Surg. 2005 Mar;54(3):269-275.
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