表皮生长因子对肠吻合口愈合影响的实验研究

目的　探讨重组人表皮生长因子 (rhEGF)对家兔小肠吻合口愈合的促进作用。方法　将 4 8只实验兔随机均分为实验组及对照组 ,均行近端小肠部分切除再吻合术 ,实验组动物于吻合时行rhEGF黏膜下注射。行外周血WBC计数 ,观察吻合口胶原纤维及羟脯氨酸的合成以及吻合口漏发生率。结果　两组术后 3d、5d及 7d与术前比较WBC略有升高 ,但差异无显著性意义 (P>0 .0 5 )。实验组吻合口漏发生率为 4 .3% ,而对照组为16 .7%。实验组术后 3d、5d及 7d胶原纤维面积密度较对照组明显增多 ,吻合口周围成纤维细胞明显增多 ,核大、浓染且胞浆丰富。实验组吻合口组织新生血管较多且有正常腺管结构 ,而对照组黏膜细胞结构破坏重。羟脯氨酸生成在术后 5d及 7d实验组与对照组相比差异有显著性意义 (P<0 .0 5 )。结论　炎症反应存在于创伤修复的全过程 ,但EGF局部应用对全身炎性反应的影响不大。rhEGF有促进创伤愈合、细胞向创面迁移的作用 ,使成纤维细胞增多 ,胶原纤维合成及转运加快 ,同时促进创面新生血管产生 ,可有效促进吻合口的愈合 ,防止吻合口漏的发生。     

碱性成纤维细胞生长因子对胆肠吻合口愈合的影响

目的　观察碱性成纤维细胞生长因子( basic fibroblast growth factor,b FGF)对胆肠吻合口愈合过程的影响,预防术后吻合口狭窄。　方法　选用健康杂种犬31只,随机分为实验组16只,对照组15只。通过制作犬胆总管十二指肠吻合模型,术后1周内吻合口局部应用b FGF(实验组)及生理盐水(对照组)。术后3d,1、3周,3、6个月( n=3)分别取材行HE及Masson染色组织学观察,吻合口瘢痕组织羟脯氨酸含量测定。　结果　实验组较对照组愈合时间明显缩短。组织学见实验组肉芽组织中成纤维细胞及毛细血管增生,上皮增生明显加快,1周时开始修复,3周时基本完成,瘢痕亦已基本定型,胶原纤维排列整齐有序,较快( 2～3周左右)进入塑形期;对照组术后3周时胶原纤维排列杂乱,呈旋涡状。电镜观察实验组肉芽组织中细胞功能旺盛,胞浆丰富,粗面内质网发达。瘢痕组织羟脯氨酸含量术后各时间点实验组均小于对照组,差异有统计学意义( P<0 .0 5 )。　结论　吻合口局部应用b FGF可预防术后胆肠吻合口狭窄     

腹腔化疗对大鼠结肠吻合口愈合的影响

目的探讨术后早期腹腔化疗(EPIC)单用5-Fu和联合使用甲酰四氢叶酸钙(LV)对大鼠结肠吻合口愈合的影响.方法 45只Wistar大鼠制成结肠吻合口模型,随机分为生理盐水(NS)组、5-Fu组和5-Fu+LV 3组,各组15只,于术后1～5 d每天腹腔分别注入NS 20 ml/(kg*d)和5-Fu 20 mg/(kg*d)+NS 20 ml/(kg*d)及5-Fu 20 mg/(kg*d)+LV 10 mg/(kg*d)+NS 20 ml/(kg*d),于术后第7 d切取吻合口标本,观察吻合口并发症并测定吻合口破裂压(ABP)和吻合口羟脯胺酸(HPC)含量.结果生理盐水组发生切口部分裂开1例,吻合口漏1例; 5-Fu组发生吻合口漏4例,死亡2例; 5-Fu+LV组发生吻合口漏2例,死亡1例,各组间相应指标比较差异均无显著性意义.ABP生理盐水组为(169.1±32.6) mm Hg (1 mm Hg=0.133 kPa),5-Fu组为(116.8±25.5) mm Hg,差异有显著性意义(P＜0.01); 5-Fu+LV组为(154.9±31.2) mm Hg,与5-Fu组比较,P＜0.05.HPC生理盐水组为(1.54±0.28) μg/mg,5-Fu组为(0.92±0.33) μg/mg (P＜0.01); 5-Fu+LV组为(1.24±0.29) μg/mg, 与5-Fu组比较,P＜0.05.结论用5-Fu行术后早期腹腔化疗对结肠吻合口的愈合有明显影响,联合使用LV可减轻5-Fu对结肠吻合口愈合的影响.     

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。     

套入空肠段肠粘膜破坏对胰肠吻合口愈合的影响

目的：从术后胰漏的发生率和组织病理学角度,比较胰套入空肠段粘膜破坏与否对吻合口愈合的影响。方法：①１０只健康杂种犬分为２组,均行胰尾切除空肠单层套入吻合。一组行套入段肠粘膜全层电灼破坏,另一组不破坏肠粘膜。术后取胰肠吻合口标本行组织病理学检查;②统计分析本院１９８９年１月～２０００年５月行胰肠套入吻合病例中,套入段肠粘膜破坏组与不破坏组的胰漏发生率。结果：两组犬吻合口组织病理学检查显示,肠粘膜破坏组套入段肠壁与胰腺包膜愈合佳,而肠粘膜不破坏组套入段肠壁与胰腺包膜愈合不完全。临床分析显示,肠粘膜破坏组胰漏发生率为２．７％,不破坏组为１６．４％,两组差异显著（Ｐ＜０．０５）。结论：胰套入段空肠粘膜破坏,使肠壁失去分泌功能,与胰腺包膜较可靠地愈合,可减少胰漏发生率。     

胆肠吻合术后吻合口狭窄的非手术治疗

目的：探讨胆肠吻合口狭窄非手术治疗的方法和疗效。方法：8例经皮下盲袢、13例经T管窦道进入胆道镜，先气囊扩张狭窄，再取狭窄上方结石，瘢痕性狭窄置硬塑管支撑3-6个月；恶性狭窄胆道镜引导置金属支架。12例行PTCD；恶性狭窄不伴结石，放射介入置金属支架；如有结石或瘢痕狭窄，先扩张窦、后经PTCS取石或置金属支架、硬塑管。全组气囊扩张19例、置硬塑管5例、置金属支架9例。结果：33例中24例良性狭窄，扩张19例、置硬塑管5例均解除梗阻，9例恶性狭窄8例置金属支架解除梗阻。15例伴有结石取净结石。全组无严重并发症。结论：借助胆道镜的非手术方法在治疗胆肠吻合术后吻合口狭窄中创伤小、副损伤少、疗效确切。     

高压氧对大白鼠颈动脉吻合口愈合的影响

目的　观察高压氧对大白鼠颈动脉吻合口愈合的影响。方法　 3 6只SD大白鼠 ,建立切断颈动脉后再吻合的模型。实验组 :术后高压氧治疗共 2 4只大鼠。对照组 :术后不作处理共 12只大鼠。术后 1、3、5、7d 4个时间组处死动物 ,取颈动脉样本 ,行光镜和免疫组化观察。用计算机图像分析系统比较血管各层的厚度。结果　术后 1、3d两组颈动脉内膜、中膜和外膜的厚度 ,无明显差别 (P >0 .0 5 )。术后7d ,对照组颈动脉中膜、外膜的厚度均大于实验组 (P <0 .0 5、P <0 .0 1)。免疫组化结果证实对照组的外膜有明显的炎症反应及纤维母细胞增生。结论　高压氧可减少炎症和纤维母细胞的增生 ,有促进动脉吻合口的愈合作用。     

胆肠吻合术后吻合口狭窄的非手术治疗

目的 探讨胆肠吻合口狭窄非手术治疗的方法和疗效。方法8例经皮下盲袢、13例经T管窦道进入胆道镜,先气囊扩张狭窄,再取狭窄上方结石,瘢痕性狭窄置硬塑管支撑3-6个月;恶性狭窄胆道镜引导置金属支架。12例行PTCD;恶性狭窄不伴结石,放射介入置金属支架;如有结石或瘢痕狭窄,先扩张窦道、后经PTCS取石或置金属支架。硬塑管。全组气囊扩张19例、置硬塑管5例、置金属支架9例。结果33例中24例良性狭窄,扩张19例、置硬塑管5例均解除梗阻,9例恶性狭窄8例置金属支架解除梗附。15例伴有结石者取净结石。全组无严重并发症。结论 借助胆道镜的非手术方法在治疗胆肠吻合术后吻合口狭窄中创伤小、副损伤少、疗效确切。     

生物可分解肠吻合环在梗阻性结肠癌根治术中的应用

目的回顾性总结吻合环在结肠癌并发肠梗阻行结肠癌根治术一期吻合中的应用经验。方法通过分析2001年2月-2004年8月21例梗阻性结肠癌根治术中应用吻合环病人的临床资料。结果本组病例均一次性获得成功。无吻合口漏、出血及吻合口狭窄。结论在梗阻性结肠癌根治术消化道重建中，与传统手工吻合相比，吻合环具有方便、快捷、可靠等优点。大大提高了操作效率，缩短了手术时间，有利于防止吻合口漏或狭窄等并发症。     

"自助式"食管扩张法治疗术后吻合口狭窄

1998年 10月至 2 0 0 3年 1月 ,我们使用“自助式”食管扩张方法为 2 6例食管癌术后吻合口狭窄的病人施行了扩张治疗 ,效果良好。现介绍使用方法并总结应用初步体会。临床资料　本组 2 6例中男 2 2例 ,女 4例 ;年龄 34～ 77岁 ,平均 6 1 3岁。均为食管癌食管部分切除食管胃吻合术后吻合口狭窄病例。吞咽困难程度 ,按Neuhaus分级〔1〕:IV级 3例 ,III级 8例 ,II级 8例 ,I级 7例。扩张治疗前均行上消化道造影及纤维胃镜检查 ,除外食管功能性障碍和吻合口肿瘤复发。扩张治疗距手术 1 5～ 98 0个月 ,平均 10 5个月。医用高分子材料制成的扩…     

环加氧酶2在人结直肠癌中的表达及其与肿瘤血管形成的关系

目的探讨环加氧酶2(Cox-2)在结直肠癌中的表达及其与肿瘤血管内皮生长因子(VEGF)表达的关系。方法选取2001年2～9月间在我院手术治疗的35例结直肠癌患者,采用逆转录聚合酶链反应(RT-PCR)的方法,检测肿瘤组织中Cox-2与VEGF的表达,并对结直肠癌Cox-2表达与肿瘤生物学特性的关系进行研究。结果(1)80.0%的肿瘤组织Cox-2表达阳性,31.4%的正常组织表达阳性(P<0.01);(2)肿瘤直径在3～6cm者Cox-2表达率明显高于直径超过6cm者(P=0.0334);(3)高分化组Cox-2表达率较高,而A/B期结直肠癌其表达高于C/D期结直肠癌,但差异均无显著性意义(P>0.05);(4)与Cox-2表达阴性组比较,Cox-2表达阳性组VEGF表达明显增高(25/27),差异有显著性意义(P=0.0030)。结论Cox-2在本组结直肠癌的表达率为80%,且与肿瘤的大小及VEGF表达相关。     

抗血管生成药物Endostatin和SU6668联合氟尿嘧啶对结肠癌的影响

目的探讨血管生成抑制剂Endostatin和SU6668联合氟尿嘧啶（5-FU）对结肠癌生长和转移的抑制作用，并探讨其作用机制。方法建立人结肠癌裸鼠原位种植转移模型。将60只荷瘤鼠随机分为5组，每组12只。种植12d后分别自腹腔内注射生理盐水（对照组）、Endostatin（E组）、SU6668（S组）、Endostatin加SU6668（E加S组）、Endostatin加SU6668加5-FU（E加S加F组），1次／d，共4周。种植后第6周末处死动物，测量原位肿瘤瘤重、抑瘤率和肿瘤微血管密度（MVD），观察肿瘤肝腹膜和区域淋巴结转移及腹水出现情况。结果对照组、E组、S组、E加S组、E加S加F组抑瘤率分别为0、64．9％、63．5％、76．4％和88．2％；MVD分别为（18．10±5．65）、（2．75±0．75）、（3．17±0．58）、（0．94±0．42）和（0．36±0．45）；腹膜转移率分别为90％、16．7％、25％、0和0；区域淋巴结转移率分别为90％、0、0、0和0。E组、S组、E加S组、E加S加F组与对照组相比，结肠癌生长和转移受到明显抑制（P〈0．05）；尤以E加S加F组明显（P〈0．01）。结论Endostatin和SU6668联合5-FU具有协同作用，能更有效地抑制结肠癌的生长和转移。     

Adverse effects of the antiangiogenic agent angiostatin on the healing of experimental colonic anastomoses

Background Antiangiogenic cancer therapy is likely to be administered long term for sustained suppression of tumor outgrowth. Surgeons will encounter more patients undergoing such therapy. Therefore, it is essential to know the effects of antiangiogenic agents on physiological angiogenesis, as occurs during the healing of colonic anastomoses. Methods Angiostatin was generated from human plasma and administered continuously. In 38 mice, the right colon was anastomosed after transection: group 1 (n=13), anstomotic healing under angiostatin treatment from surgery until death (day 7); group 2 (n=13), phosphate-buffered saline controls. For healing on discontinuation of treatment, group 3 (n=6) received angiostatin treatment preceding surgery during 4 days; group 4 (n=6) included controls. On day 7, all mice were inspected for signs of anastomotic leakage. Bursting pressure measurements were performed to test anastomotic strength. Neovascularization was assessed semiquantitatively by immunohistochemistry. Results Mice treated with angiostatin postoperatively showed significantly more signs of leakage, more adhesions and peritonitis. One mouse died on day, 5. Five mice had paralytical ileus. The bursting pressure in group 1 was 135±20 mm Hg, versus 175±12 mm Hg in group 2 (mean ±SEM). Significantly fewer new vessels were found surrounding the anastomosis in the treated group (6.6±.9) versus controls (16±1.6). All controls, as well as those animals treated with angiostatin only until surgery (group 3), displayed normal healing and showed no signs of peritonitis or ileus. Conclusions Angiostatin impairs anastomotic healing in mice. However, on discontinuation of antiangiogenic therapy, normal anastomotic healing is promptly restored.     

Effects of the amniotic membrane on healing of colonic anastomoses in experimental left-sided colonic obstruction

Purpose  

We investigated the effects of the amniotic membrane on experimental primary colonic anastomoses of colonic obstruction in rats.     

SU5416对结肠癌生长和转移抑制作用的实验研究

目的研究血管生成抑制因子SU5416对结肠癌生长和转移的抑制作用.方法采用人结肠腺癌细胞株SW1116完整组织块裸鼠原位种植,建立类似于临床的结肠癌转移裸鼠模型.分别自腹腔注射生理盐水(对照组)、氟尿嘧啶(5Fu组)、SU5416制剂(SU5416组)、5Fu与SU5416联合应用(联用组),共用7周.种植后第8周处死动物,测量原位肿瘤瘤重、抑瘤率、肿瘤微血管密度(MVD)、结肠癌细胞凋亡指数(AI),观察肿瘤细胞腹膜、肝、其他脏器转移及腹水情况.结果对照组、5Fu组、SU5416组、联用组的原位肿瘤瘤重分别为(138±0.42)g、(0.71±0.26)g、(0.25±0.13)g、(0.16±0.09)g;抑瘤率分别为0、48.6%、81.9%、88.4%;MVD分别为134±4.9、11.7±4.2、2.6±1.4、0.94±0.5;AI分别为(3.59±2.46)%、(6.81±5.97)%、(12.83±4.56)%、(20.18±8.91)%;腹膜转移率分别为90.9%、46.5%、25.0%、0;肝转移率分别为72.7%、33.3%、16.7%、0.5Fu组、SU5416组、联用组分别与对照组相比,组间结肠癌生长和转移的抑制作用差异有显著性意义(P<0.05).结肠癌的生长和腹膜、肝转移受到明显抑制(P<0.05).结论SU5416通过抗肿瘤血管生成,诱导结肠癌细胞凋亡,对体内结肠癌生长和转移具有强烈的抑制作用,且与传统化疗药物联用可起协同作用.     

Experimental studies on the healing of colonic anastomoses

The leakage of colonic anastomoses is a potentially devastating surgical complication. Several factors, such as bowel preparation prior to surgery, surgical technique, nutritional status, and intervening pathological conditions, have been identified as significantly influencing the healing of colonic anastomoses. Due to the multifactorial nature, it is difficult to investigate the mechanisms of occurrence and prevention of colonic dehiscence in the clinical setting. For this reason, many experimental models have been used to study colonic healing and the pathogenesis of anastomotic failure. This report reviews the use of animal models for the study of colonic anastomotic healing. Special emphasis is devoted to the rationale for selecting animal models, parameters of healing, factors influencing anastomotic healing as well as the clinical potential of dietary and pharmacologic manipulations proposed to improve colonic healing.     

Effects of trapidil on the healing of colonic anastomoses in an experimental rat model

Background: Trapidil has various properties including vasodilatation, inhibition of lipid peroxidation and platelet aggregation as well as, and reduction of, the inflammatory response to injury. The aim of the present study was to investigate the effects of trapidil on dexamethasone‐impaired colonic anastomotic healing in an experimental rat model. Methods: Twenty‐four Wistar rats underwent colonic transsection and primary anastomosis. Rats were divided into four groups of six: group 1 (G1), control; group 2 (G2) trapidil, 8 mg/kg per day intravenously; group 3 (G3) dexamethasone, 0.1 mg/kg per day intramuscularly; and group 4 (G4) dexamethasone 0.1 mg/kg intramuscularly and trapidil 8 mg/kg intravenously per day, for 1 week. Anastomotic bursting pressure, hydroxyproline level, histopathological grading, malondialdehyde and nitrite/nitrate levels were determined. Results: Dexamethasone‐impaired anastomotic healing was found to be improved by trapidil administration in terms of anastomotic bursting pressure and hydroxyproline content (P = 0.026, and P = 0.017). In addition, histopathological examination revealed an increase in fibroblast proliferation and collagen deposition (P = 0.004, and P = 0.015) and a decrease in leucocyte infiltration (P = 0.004). Moreover, serum nitrite/nitrate and malondialdehyde levels decreased when G3 was compared to G4 (P < 0.001, P= 0.38). Conclusions: Trapidil may improve the dexamethasone‐impaired anastomotic healing due to its preventive effects on inflammatory response and lipid peroxidation in rats.     

Effects of 5-fluorouracil and zinc on healing of colonic anastomoses in rabbits.

OBJECTIVE: To find out if 5-fluorouracil (5-FU) given intraperitoneally to rabbits impaired the healing of colonic anastomoses, and whether giving zinc might reverse the effect. DESIGN: Laboratory study. SETTING: Teaching hospital, Turkey. ANIMALS: 32 New Zealand white rabbits. INTERVENTIONS: All animals had 1cm of large bowel resected 10cm proximal to the peritoneal reflection and continuity restored by end-to-end anastomosis. They were divided into four groups and given intraperitoneal injections of saline (control group), 5-FU 10mg/kg/day in a concentration of 5mg/ml saline (5-FU alone group), zinc 2mg/kg/day (zinc alone group), and the same doses of 5-FU and zinc (5-FU + zinc group). The injections were given immediately after operation and daily for 4 days. The rabbits were killed at 7 days. MAIN OUTCOME MEASURES: Bursting pressures, tissue hydroxyproline concentrations, tissue zinc concentrations, and light and electron microscopic appearances. RESULTS: Six rabbits died of the complications of anaesthesia and 4 of sepsis leaving 7, 6, 7, and 6 rats in the four groups respectively. Mean (SD) anastomotic bursting pressures were significantly reduced in the 5-FU group compared with controls (5 (2) compared with 7 (1) mm Hg, p: 0.05) and collagen synthesis (indicated by reduced tissue hydroxyproline concentrations) was also decreased (7.1 (0.9) compared with 9.1 (1.5), p < 0.05). Rabbits given 5-FU + zinc had significantly higher bursting pressures than those given 5-FU alone (9 (2) compared with 5 (2), p: 0.01). Bursting pressures were also significantly higher in those given zinc alone, but hydroxyproline concentrations were similar to those in the control group. Histological examination showed that 5-FU alone significantly impaired the healing process, and those in the 5-FU + zinc group healed better than those in the 5-FU alone group. CONCLUSIONS: 5-FU given intraperitoneally significantly impaired the healing of colonic anastomoses in rabbits, and zinc reversed this effect.     

结直肠癌组织中巨噬细胞表达胸苷磷酸化酶并与血管新生相关

目的探讨结直肠癌组织中胸苷磷酸化酶(dThdPase)表达与血管新生的相互关系。方法采用抗dThdPase、抗巨噬细胞标记物CD68和抗血管内皮细胞标记物CD34的单克隆抗体,对40例结直肠癌手术切除标本进行免疫组织化学染色分析,对其中27例标本同时测定其癌组织和周围正常组织的dThdPase活性(HPLC法)。并应用ELISA法分别检测结直肠癌细胞系LS174T、CloneA、Colo320、CX-1、Lovo、MIP101和类巨噬细胞系THP-1和U937的dThdPase蛋白含量。结果结直肠癌组织中的dThdPase活性明显高于周围正常肠组织(P<0.01)。dThdPase阳性细胞几乎都是癌巢周围的间质细胞,特别是肿瘤相关巨噬细胞(TAM)。且TAM与dThdPase阳性细胞的分布区域几乎完全一致。癌巢周围新生血管数明显多于正常肠黏膜组织(P<0.01)。TAM计数、dThdPase阳性间质细胞计数和微血管计数3者互成正相关。除LS174T检出微量和Lovo检出少量dThdPase蛋白外,其他4株癌细胞未检出。而THP-1和U937的dThdPase蛋白含量分别为18.2U/mg和19.3U/mg。结论结直肠癌组织中增高的dThdPase活性主要由TAM表达,增多的TAM与结直肠癌的血管新生相关。     

�󳦰��γɹ���������Ѫ����������ϸ����ֳ�������ı仯

目的 探讨大肠癌从大肠腺瘤伴轻度不典型增生到重度不典型增生到腺癌发展过程中肿瘤血管生成、细胞增殖、细胞凋亡的变化及其内在联系。方法 应用免疫组化方法测定增殖细胞核抗原(PCNA)和微血管密度(MVD)，用TUNEL法测定细胞凋亡。结果 (1)从腺瘤到腺癌的发展过程中，细胞增殖水平逐渐增高，细胞凋亡逐渐减少，MVD逐渐增多。而且腺瘤伴轻度不典型增生的肿瘤微血管与腺瘤伴重度不典型增生相比不仅形态上有差异，在数量差异也有显著性。(2)轻度不典型增生腺瘤PCNA与AI呈正相关性。(3)将所有大肠肿瘤作为一组分析，发现MVD与AI具有负相关性。结论 (1)血管生成抑制肿瘤细胞凋亡，促进肿瘤细胞增殖。(2)血管生成开关可能是在腺瘤伴轻度不典型增生向重度不典型增生和腺癌的转化过程中启动的。