促进肠吻合愈合制剂应用研究进展

肠吻合术在普通外科手术中占有着重要地位,临床肠吻合术仍然存在着一定的出血梗阻及吻合口漏发生率。在保证基本吻合并预防控制腹腔感染及改善全身营养状况的基础上,局部或者全身应用一些制剂如纤维蛋白胶、生长激素及外源性生长因子等或其他一些临床药物亦能大大降低肠吻合并发症发生率,促进肠吻合愈合。     

如何促进严重腹膜炎肠吻合口愈合

肠损伤破裂或肠手术吻合口／缝合口溢漏并发腹膜炎是一种严重的并发症，如处理不及时或处理失当，可导致全身性感染或后遗肠外瘘，有较高的致病率、病死率。及时进行确定性手术，去除破损肠段或溢瘘的肠吻合口、缝合口是合理的首选治疗措施。但是，很多患者由于诊断不及时，医疗条件受限等因素，未能在事件发生或症状出现的第一时间内被认识和处理。待进行针对性处理时，病变已经明显，腹腔有数百至数千毫升的肠液性脓液，腹膜及腹腔内脏器呈广泛感染性炎症病变，充血、水肿，有纤维性分泌物覆盖。     

纤维蛋白胶和生长激素促进腹腔感染条件下大鼠肠吻合口愈合的研究

目的应用纤维蛋白胶 (fibringlue ,FG)、生长激素 (growthhormone ,GH)于腹腔感染条件下的大鼠小肠吻合 ,探讨其有效性和作用机制。方法将大鼠分为正常对照组和在腹腔感染模型下行标准肠吻合组 (丝线吻合 12针 )、简易吻合组 (丝线吻合 4针 )、简易吻合 +FG组、简易吻合 +GH组、及简易吻合 +FG +GH组共 6组 ,于小肠局部切除吻合术后第 1、3、5天分别观察、测定其吻合口不良愈合率、吻合口爆破压、吻合口羟脯氨酸浓度等指标。结果在感染条件下标准吻合组吻合口爆破压于术后第 1天至第 3天分别为 (18± 10 )mmHg和 (36± 11)mmHg ,不良愈合率达 30 % ;而使用FG行胶合组吻合口强度显著提高 ,分别为 (32± 7)mmHg和 (6 5± 9)mmHg ,不良愈合显著减少 ,仅为11 76 %。在胶合的基础上加用GH与未加用GH组比较 ,羟脯氨酸浓度无显著性差异。结论大鼠在腹腔感染条件下可以使用FG实施小肠肠吻合并减少并发症的发生 ,加用GH后早期疗效提高不显著     

局部缓释血管内皮生长因子促进肠吻合口愈合的研究

目的探讨应用生物蛋白胶缓释血管内皮生长因子(VEGF)促进肠吻合口愈合的有效性。方法通过在兔盲肠穿孔建立腹腔感染的动物模型,12h后行肠切除及肠吻合。动物分成4组(每组32只),各组吻合口表面所涂试剂不同:生理盐水组、生物蛋白胶组、VEGF组及VEGF+生物蛋白胶组。于手术后第3、5、7及14天统计各组吻合口漏发生情况,测量未发生吻合口漏的动物的吻合口破裂压,检测吻合口组织羟脯氨酸含量及VEGF表达情况。结果生物蛋白胶组及VEGF组的吻合口漏总发生率低于对照组,但差异无统计学意义(P0.05),而VEGF+生物蛋白胶组则明显低于对照组(P0.05)。至术后第14天,VEGF+生物蛋白胶组的吻合口破裂压、吻合口组织羟脯氨酸含量及VEGF蛋白表达阳性细胞率(除VEGF组)均较其余3组明显升高(P0.05,P0.01)。结论应用生物蛋白胶局部缓释VEGF能够促进肠吻合口愈合,降低吻合口漏的发生率。     

纤维蛋白粘合剂预防肠吻合口瘘的实验研究

目的 观察小肠切除、肠吻合后局部用国产纤维蛋白粘合剂在保进吻合口愈合,预防吻合口瘘中的作用。方法 实验动物随机分为两组,对照组兔在肠切除吻合后表面喷涂生理盐水实验组喷涂纤维蛋白粘合剂,术后第１、３、７、１４ｄ切取含吻合的肠管,分别测定吻合口破裂压、吻合口组织羟脯氨酸和胶原量。结果 术后组动物均无吻合口瘘,术后第１、３ｄ,实验组兔肠吻合破裂压高于对照组（约５ｍｍＨｇ）,局部肠组织羟脯氨酸,胶原量也多于对照组,但差异不显,结论 纤维蛋白粘合剂可保进成纤维细胞增殖和胶原合成,对预防吻合口瘘有一定意义。     

人重组生长激素与肠外营养

作为基因工程的一项重要产物，人重组生长激素具有多种功能，能显著提高肠外营养的效率，本文综述其在肠牙营养条件下，对机体代谢的作用，作用机制及其药代动力学。     

术后早期腹腔化疗下联合应用生长激素和生物蛋白胶对结肠吻合口愈合的影响

目的研究联合应用生长激素(GH)和生物蛋白胶(FS)对术后早期腹腔化疗条件下结肠吻合口愈合的影响。方法Wister大鼠48只,随机分为4组：对照组,单纯行肠切除吻合；腹腔化疗组(5-FU组),术后连续3 d腹腔内注射氟尿嘧啶(5-FU)(20 mg·kg~(-1)·d~(-1))；FS组,术中应用FS、术后给予早期腹腔化疗；GH联合FS组,术中应用FS、术后给予GH(1 mg·kg~(-1)·d~(-1))及早期腹腔化疗。术后8 d处死各组大鼠,剖腹切取吻合口进行评分(评分越高提示吻合口与周围组织的粘连越重)和测量吻合口破裂压力及进行吻合口组织学评分。结果GH联合FS组的吻合口评分2．00,低于FS组(2．13)和对照组(2．38),但P＞0．05,差异无统计学意义；GH联合FS组显著低于5-FU组的2．75,P＜0．05；差异有统计学意义。GH联合FS组的吻合口破裂压力229．9475,高于对照组(199．7525)和FS组(199．4338),P＜0．05；显著高于5-FU组(171．7938),P＜0．01。GH联合FS组的吻合口组织学评分2．9,高于FS组(2．3)和对照组(2．1)及5-FU组(1．7),P＜0．05。结论联合应用GH和FS能提高吻合口愈合强度,促进术后早期腹腔化疗条件下结肠吻合口的愈合。     

砂仁对大鼠小肠吻合口愈合的影响

目的：探讨砂仁对大鼠小肠吻合口愈合的影响。方法：90只SD大鼠,随机分为模型组、砂仁组和普鲁本辛组,每组30只,均行小肠端端吻合。砂仁组在造模后灌胃给予砂仁溶液（按生药计,0.25g/kg）,普鲁本辛组在造模后灌胃给予普鲁本辛（3.5mg/kg）溶液。术后3、5、7d观察小肠吻合口病理学改变、吻合口爆破压、羟脯氨酸含量 术后7d测量小肠系膜微静脉血流流速。结果：砂仁组吻合口局部炎症轻于其他两组,胶原纤维排列较好 术后5,7d吻合口羟脯氨酸、爆破压高于模型组和普鲁本辛组（P〈0.05） 术后7d肠系膜微静脉血流流速高于模型组和普鲁本辛组（P〈0.05）。结论：砂仁口服能够促进大鼠小肠吻合口的愈合。     

Effects of High Bilirubin Levels on the Healing of Intestinal Anastomosis

Purpose This article analyzes the relationship between high biluribin levels and anastomotic healing in the long term.Methods Ninety rats were randomly divided into six groups. The first three groups were jaundiced while the other three were unjaundiced. In the jaundiced groups, the rats’ common bile ducts were ligated for 1, 2, and 3 weeks and ileal anastomosis was performed. In unjaundiced groups, only anastomosis was performed for 1, 2, and 3 weeks. At the end of the study, the values of the bursting pressures and hydroxyproline levels were determined in all groups. The bilirubin levels were also followed in jaundiced groups.Results In the jaundiced groups, the mean hydroxyproline contents were 7.5 ± 4.0, 6.3 ± 2.3, and 5.6 ± 2.1 (µHP/mg tissue) and the mean bursting pressures were 178 ± 38, 171 ± 23, and 164 ± 26 mmHg at weeks 1, 2, and 3, respectively. In the unjaundiced groups, the mean hydroxyproline contents were 7.6 ± 3.2, 8.1 ± 3.0, and 8.6 ± 2.5 (µHP/mg tissue) and the mean bursting pressures were 181 ± 28, 183 ± 21, and 186 ± 22 mmHg at weeks 1, 2, and 3, respectively. The bilirubin levels were 3.8 ± 1.5, 6.5 ± 2.3, and 11.2 ± 2.9 mg/dl at weeks 1, 2, and 3, respectively, in the jaundiced groups and 0.6 ± 0.06, 0.6 ± 0.03, and 0.7 ± 0.04 mg/dl in the unjaundiced groups.Conclusion This study showed that the bilirubin levels can lead to a deterioration depending on the magnitude of the rise in the bilirubin levels.     

The Effects of Hyperbaric Oxygen Therapy on Colonic Anastomosis in Rats With Peritonitis

The aim of this study is to investigate the healing effect of hyperbaric oxygen (HBO) on colonic anastomoses in the presence of experimentally induced peritonitis. Thirty-two rats were allocated randomly into short-term anastomosis (STA), short-term anastomosis + HBO treatment (STA+HBO), long-term anastomosis (LTA), and long-term anastomosis + HBO (LTA+HBO) treatment groups. The STA and LTA groups were administered fluid resuscitation and antibiotics for 3 and 7 days, respectively, whereas the HBO treatment groups received additional HBO therapy for 3 and 7 days, respectively. The rats were reoperated on the third and the seventh days of anostomoses for evaluation. The bursting pressures in STA+HBO and LTA+HBO therapy groups were significantly higher than those in groups with anastomoses alone (p <. 001 and p <. 01). HBO therapy did not affect the fibrotic index neither in STA nor in LTA groups (p >. 05 for both); however, it was significantly higher in LTA+HBO group than that in STA+HBO group (p <. 05). The hydroxyproline level was significantly higher in LTA group than in STA group (p <. 05), yet HBO therapy did not affect the hydroxyproline levels in STA or LTA groups (p >. 05 for both). It is concluded that hyperbaric oxygen treatment has positive effects on colonic anastomotic healing in case of peritonitis.     

Effect of Peritoneal Lavage with Taurolidine on Primary Colonic Anastomosis in a Rat Model of Secondary Peritonitis

Purpose The reported antibacterial, antiendotoxic, and antiadhesive effects of taurolidine prompted us to study the benefits of intraperitoneal lavage with taurolidine on primary colonic anastomosis in a rat model of secondary peritonitis. Methods We induced peritonitis in 40 rats by injecting Escherichia coli isolate intraperitoneally. We performed colonic resection and primary anastomosis 5 h later, after lavage with either taurolidine or saline solution. After the rats were killed, on postoperative day (POD) 3 (n = 10) or 7 (n = 10), we measured the bursting pressures and hydroxyproline levels, then examined the resected specimens histologically. Results Bursting pressures and tissue hydroxyproline levels were significantly higher in the taurolidine group than in the control group on PODs 3 and 7 (P < 0.05). Histopathological examination revealed significantly higher fibroblastic activity in the taurolidine group. Conclusions The higher bursting pressures and tissue hydroxyproline levels in the rats given taurolidine showed the positive effect of taurolidine on anastomotic strength in secondary peritonitis. Taurolidine is a novel antibiotic with both antibacterial and antiendotoxic effects. Intraperitoneal lavage with taurolidine solution may reduce the risks associated with performing primary colonic anastomosis in patients with secondary peritonitis.     

重组人生长激素在肝硬变围手术期应用的临床研究

目的探讨重组人生长激素（rhGH）对肝硬变门静脉高压症患者术后肝功能和营养代谢的影响。方法将2003年2月至2004年1月期间我院收治的48例肝硬变患者随机均分为rhGH组和对照组，2组患者分别于术后第2d给予rhGH或生理盐水，共7d，检测2组患者的白蛋白水平、肝功能及血糖水平。结果rhGH组治疗后第7d起，血浆白蛋白水平明显高于对照组相应时相（P〈0．05）；血ALT、AST明显低于对照组相应时相（P〈0．05）；2组血糖含量随治疗时间延长逐渐降低，治疗后第14d恢复正常，但2组血糖治疗前、后相应时相比较差异无统计学意义（P〉0．05）；2组血浆胆红素水平于治疗前、后相应时相比较差异无统计学意义（P〉0．05）。结论rhGH可促进肝硬变门静脉高压症患者术后蛋白质的合成，纠正低蛋白血症，改善肝功能。     

Influence of Hydroxyethyl Starch on Healing of Colonic Anastomosis in a Rat Model of Peritonitis

Background: This study was designed to evaluate the role of different intravascular volume replacement regimens of HES 130/0.4 on wound healing process in left colonic anastomoses in the presence of intra-abdominal sepsis induced by murine model of cecal ligation and puncture (CLP). Methods: The left colonic anastomosis was performed in 40 rats that were divided into five groups (n = 8/group): saline controls (30 ml/kg); CLP plus saline (30 ml/kg); CLP plus HES (7.5, 15, or 30 ml/kg, respectively). Saline or HES was treated before the construction of left colonic anastomosis and on a regular daily basis. Anastomotic bursting pressures were measured in vivo on day 5. Tissue samples were obtained for analyses of hydroxyproline (HP) contents, myeloperoxidase (MPO) acivity, malondialdehyde (MDA), reduced glutathione (GSH) levels, and nuclear factor-κ B (NF-κ B) activation. The plasma levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 were also measured. Results: Intra-abdominal sepsis led to significant decreases in colonic anastomotic bursting pressures, and perianastomotic tissue HP contents and GSH levels, along with increases in perianastomotic tissue MPO activity, MDA levels and NF-κ B activation and plasma levels of TNF-α and IL-6. After treated with HES, these provoked perianastomotic tissue MPO activity, MDA levels, NF-κ B activation, and plasma levels of TNF-α and IL-6 were suppressed and GSH levels were restored, especially in 15 ml/kg HES group. Without obvious influence on systemic nutritional condition, HES 15 ml/kg but not HES 7.5 ml/kg significantly increased anastomotic bursting pressures, and perianastomotic tissue HP contents. However, HES 30 ml/kg even led to adverse effects on anastomotic bursting pressures. Conclusions: This study showed that moderate doses (15 ml/kg) of HES 130/0.4 administration significantly prevented this intraperitoneal sepsis-induced impaired anastomotic healing of the left colon. It also suggested the possibility of poorer anastomotic healing receiving HES at higher doses (30 ml/kg). Clearly, HES 130/0.4 now should not be recommended to use at a high doses postoperatively in sepsis.     

Combination of Fibrin Glue with Growth Hormone Augments Healing of Incomplete Intestinal Anastomoses in a Rat Model of Intra-Abdominal Sepsis: A Dynamic Study

This study was devised to investigate whether fibrin glue (FG) in combination with growth hormone (GH) could have a beneficial effect at a late period (14 days) after injury. Male Wistar rats, with abdominal sepsis induced by an incomplete anastomosis, were divided into three groups. In the control group, the rats got incomplete anastomoses sutured alone; in the FG and FG/GH groups, anastomoses protection was performed with application of FG alone or in combination with GH. The anastomotic bursting pressure (ABP) was significantly higher in the FG/GH group than that of the FG group on postoperative day (POD) 5 (p <. 01), while it could not be measured from POD 7 to POD 14 because of intestinal dehiscence. There was no difference between FG and FG/GH group on POD 3 and POD 5 in anastomotic tensile strength, which was significantly higher in the FG/GH group than that of the FG group from POD 7 to POD 14 (p <. 001). Hydroxyproline content of the FG/GH group was significantly higher than that of the control from POD 3 and that of the FG group from POD 5 (p <. 05). Combination of FG with GH had a synergistic effect to improve intestinal anastomotic healing over a limited 14-day course of observation.     

食管胃分层吻合法的应用与实验观察

目的通过临床和动物实验观察食管胃分层吻合法的临床应用结果及吻合口愈合质量。方法采用食管胃分层吻合法施行食管癌、贲门癌手术1024例,同期用该手术方法做动物实验并观察吻合口情况。将24只犬采用抽签法分成两组,实验组:12只,采用食管胃分层吻合法;对照组:12只,采用传统吻合方法作为对照。分别在术后5d、8d、14d和42d测量两组大体标本的吻合口口径、瘢痕长度、瘢痕厚度,组织学观察炎性细胞数、成纤维细胞数和毛细血管数,并进行表皮生长因子(EGF)和转化生长因子β1(TGF-beta1)的免疫组织化学实验(LsAB法)。结果临床结果:术后分别随访至3个月,1024例患者术后无吻合口瘘发生,仅6例发生轻度狭窄,经扩张一次缓解。实验结果:实验组黏膜对合良好、吻合口柔软、瘢痕薄,术后早期炎性细胞数和成纤维细胞数增多(P<0.05),术后第42d炎性细胞数和成纤维细胞数减少(P<0.05);对照组吻合口瘢痕厚、黏膜对合不齐、常有肌层暴露,早期炎性细胞数和成纤维细胞数较少,而术后8～14d明显增加,一直持续到术后42d仍有增加的趋势。实验组细胞因子早期活跃,高表达,至术后42d时仅有少量表达;而对照组早期表达低,术后第8d明显增加,第42d仍有较高表达。结论食管胃分层吻合法患者吻合口愈合质量高、瘢痕小,其细胞增生和生长因子的表达有利于伤口正常愈合且达到了一期愈合的标准,值得临床推广应用。     

生长激素减轻梗阻性黄疸时肠菌及内毒素移位的实验研究

目的　探讨生长激素减轻梗阻性黄疸时肠细菌及内毒素移位的作用及其机理。方法　将 60只大鼠随机均分为假手术组 (SO组 )、梗阻性黄疸组 (OJ组 )及生长激素组 (rhGH组 ) ,rhGH组每天皮下注射Saizen 0 .75u/kg ,SO组及OJ组则用等量生理盐水作对照。检测各组血内毒素水平 ,并取腹水、血及肠系膜淋巴结、肝脏、肾脏和脾脏作细菌培养 ,同时测定末段回肠之粘膜厚度及绒毛高度。结果　OJ组血内毒素值为 (0 .77± 0 .0 3 )u/ml,较rhGH组的 (0 .40±0 .0 2 )u/ml明显增高 (P <0 .0 1) ,rhGH组接近SO组的 (0 .3 3± 0 .0 3 )u/ml水平。OJ组细菌移位率为 5 8.8% ,较rhGH组 (10 .0 % )明显增高 (P<0 .0 1) ,rhGH组与SO组 (0 )比较 ,P>0 .0 5。rhGH组绒毛高度为 (2 3 7.5 2± 13 .65 ) μm ,较OJ组的(183 .3 9± 11.0 9) μm明显增高 (P<0 .0 1) ;rhGH组粘膜厚度为 (3 2 0 .81± 14 .3 4) μm ,较OJ组的 (2 5 5 .62± 16.5 8) μm增厚(P <0 .0 1)。结论　生长激素对肠粘膜屏障具有明显的保护作用 ,可有效减轻梗阻性黄疸时肠菌及内毒素的移位。     

胰性脑病临床治疗的探讨

目的：探讨胰性脑病（PE）临床治疗方法,降低重症急性胰腺炎（SAP）的病死率。方法：SAP伴发的早期可疑PE7例,采用重组人生长激素（ rhGH）治疗,4U／次,每日2次,5－7天。联合用药组以生长抑素合用rhGH治疗SAP,共13例,剂量及时间同早期PE组。结果：应用后rhGH24h,病人精神障碍改善,48－72h后症状消失,本组7例全部治愈。联合用药治疗SAP13例,未见PE的发生。结论：生长激素对早期PE有治疗作用,生长激素与生长抑素联合应用有可能降低PE的发生。