胶原蛋白膜用于大鼠胃壁缺损修复的可行性及有效性研究
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摘要
目的探讨引导组织再生(guide tissue regeneration,GTR)胶原蛋白膜用于大鼠胃壁全层缺损修复的可行性及有效性。方法 33只SD大鼠分为实验组(n=25)和对照组(n=8),建立胃壁全层穿孔模型,分别应用GTR胶原蛋白膜或聚乳酸(polylactic acid,PLA)膜修补。观察术后大鼠食欲、体重变化及体温,有无腹胀、腹泻及腹膜炎表现。实验组大鼠分别于术后3天、1周、2周、4周、6周处死(每次5只),对照组于术后6周处死,观察穿孔创面愈合、腹腔粘连、腹腔感染,并取穿孔部位组织进行组织病理分析。结果①33只SD大鼠均成功完成胃穿孔建模及修复术。对照组3只大鼠于术后3天内死亡(穿孔修补部位再次穿孔),实验组25只术后活动正常,食欲、体重及体温未见明显异常,无腹胀腹泻,无腹腔脓肿及消化道漏,实验组存活率[100%(25/25)]明显高于对照组[62. 5%(5/8)](Fisher检验,P=0. 010)。②实验组术后1周胃壁全层缺损闭合,黏膜面黏膜缺损面积(39. 79±0. 55) mm~2,术后2周黏膜缺损面积(7. 40±0. 43) mm~2,术后4周黏膜缺损面积(0. 91±0. 08) mm~2,术后6周黏膜完全再生,黏膜下层及肌层组织趋于正常化。对照组术后6周黏膜缺损面积(1. 39±0. 20) mm~2,显著大于实验组术后4周黏膜缺损面积(t=-5. 029,P=0. 001)。结论 GTR胶原蛋白膜作为修复骨架可有效促进细胞爬行和再生,可快速修补胃穿孔并促进愈合,再生组织无明显瘢痕,实现缺损组织和结构复原,修复效果明显优于PLA膜。
Objective To investigate the feasibility and efficacy of guide tissue regeneration( GTR) collagen membrane for repairing full-thickness defects of rat stomach. Methods A total of 33 SD rats were divided into either experimental group( n = 25)or control group( n = 8). The rats were used to establish full-thickness defects model of the gastric wall,and then respectively repaired by the GTR collagen patches or polylactic acid( PLA) patches. The rats' appetite,body weight,and body temperature were observed,as well as abdominal distension,diarrhea and peritonitis. The rats in the experimental group were randomly divided into 5 subgroups:postoperative 3 days group,postoperative 1 week group,postoperative 2 weeks group,postoperative 4 weeks group,and postoperative6 weeks group,which were sacrificed at corresponding time. The rats in the control group were sacrificed at 6 weeks after the surgery.The healing of perforated wounds,abdominal adhesions,abdominal infections were compared after being sacrificed at the corresponding time. The defect regions were collected for histopathological analysis. Results ① All the 33 SD rats with stomach defect were successfully repaired. A total of 3 rats in the control group died within 3 days( perforation happened again in the repaired places). All the rats in the experimental group( n = 25) survived well until being sacrificed at corresponding time,with no abnormity in appetite,body weight or body temperature. And no abdominal distension,diarrhea,abdominal abscess or digestive tract leakage happened. The survival rate was much higher in the experimental group [100%( 25/25) ] than the control group [62. 5%( 5/8) ]( Fisher's exact test,P = 0. 010). ②One week after surgery,the perforation was closed and the mucosal surface defect area was( 39. 79 ± 0. 55) mm~2 in the experimental group. The mucosa defect area was( 7. 40 ± 0. 43) mm~2 at the second week and( 0. 91 ± 0. 08) mm~2 at the fourth week. Six weeks after the surgery,the mucosal achieved complete regeneration. The structure of submucosal and myometrium tended to be normalized. The mucosa defect area of the control group was about( 1. 39 ± 0. 20) mm~2 at the sixth week and was much larger than the area of the experimental group at the forth week( t =-5. 029,P = 0. 001). Conclusions GTR collagen patch is more effective for cell regeneration and tissue repair than PLA patches. More importantly,the recovered defect presents less fibrosis,where tissue structure and function turn to be normal.
Objective To investigate the feasibility and efficacy of guide tissue regeneration( GTR) collagen membrane for repairing full-thickness defects of rat stomach. Methods A total of 33 SD rats were divided into either experimental group( n = 25)or control group( n = 8). The rats were used to establish full-thickness defects model of the gastric wall,and then respectively repaired by the GTR collagen patches or polylactic acid( PLA) patches. The rats' appetite,body weight,and body temperature were observed,as well as abdominal distension,diarrhea and peritonitis. The rats in the experimental group were randomly divided into 5 subgroups:postoperative 3 days group,postoperative 1 week group,postoperative 2 weeks group,postoperative 4 weeks group,and postoperative6 weeks group,which were sacrificed at corresponding time. The rats in the control group were sacrificed at 6 weeks after the surgery.The healing of perforated wounds,abdominal adhesions,abdominal infections were compared after being sacrificed at the corresponding time. The defect regions were collected for histopathological analysis. Results ① All the 33 SD rats with stomach defect were successfully repaired. A total of 3 rats in the control group died within 3 days( perforation happened again in the repaired places). All the rats in the experimental group( n = 25) survived well until being sacrificed at corresponding time,with no abnormity in appetite,body weight or body temperature. And no abdominal distension,diarrhea,abdominal abscess or digestive tract leakage happened. The survival rate was much higher in the experimental group [100%( 25/25) ] than the control group [62. 5%( 5/8) ]( Fisher's exact test,P = 0. 010). ②One week after surgery,the perforation was closed and the mucosal surface defect area was( 39. 79 ± 0. 55) mm~2 in the experimental group. The mucosa defect area was( 7. 40 ± 0. 43) mm~2 at the second week and( 0. 91 ± 0. 08) mm~2 at the fourth week. Six weeks after the surgery,the mucosal achieved complete regeneration. The structure of submucosal and myometrium tended to be normalized. The mucosa defect area of the control group was about( 1. 39 ± 0. 20) mm~2 at the sixth week and was much larger than the area of the experimental group at the forth week( t =-5. 029,P = 0. 001). Conclusions GTR collagen patch is more effective for cell regeneration and tissue repair than PLA patches. More importantly,the recovered defect presents less fibrosis,where tissue structure and function turn to be normal.
引文
1 Paspatis GA,Dumonceau JM,Barthet M,et al.Diagnosis and management of iatrogenic endoscopic perforations:European Society of Gastrointestinal Endoscopy(ESGE)position statement.Endoscopy,2014,46(8):693-711.
2 Iqbal CW,Cullinane DC,Schiller HJ,et al.Surgical management and outcomes of 165 colonoscopic perforations from a single institution.Arch Surg,2008,143(7):701-706.
3 van der Sluis FJ,Loffeld RJ,Engel AF.Outcome of surgery for colonoscopic perforation.Colorectal Dis,2012,14(4):e187-190.
4 Kume K.Endoscopic therapy for early gastric cancer:standard techniques and recent advances in ESD.World J Gastroenterol,2014,20(21):6425.
5 Verlaan T,Voermans RP,van Berge Henegouwen MI,et al.Endoscopic closure of acute perforations of the GI tract:a systematic review of the literature.Gastrointest Endosc,2015,82(4):618-628e5.
6 Spiliopoulos K,Markakis C,Tomos P,et al.Repair of gastric defects with an equine pericardial patch.Surg Today,2015,45(1):83-90.
7 Tanaka Y,Nakamura T,Fujii S,et al.Successful treatment of a perforated duodenal ulcer with polyglycolic acid sheets.Gastrointest Endosc,2017,85(6):1299-1300.
8 Tonai Y,Takeuchi Y,Akita H,et al.Iatrogenic duodenal perforation during underwater ampullectomy:endoscopic repair using polyglycolic acid sheets.Endoscopy,2016,48(S1):E97-98.
9 Sakaguchi Y,Tsuji Y,Yamamichi N,et al.Successful closure of a large perforation during colorectal endoscopic submucosal dissection by application of polyglycolic acid sheets and fibrin glue.Gastrointest Endosc,2016,84(2):374-375.
10 Qasim SB,Najeeb S,Delaine-Smith RM,et al.Potential of electrospun chitosan fibers as a surface layer in functionally graded GTR membrane for periodontal regeneration.Dent Mater,2017,33(1):71-83.
11 Faggion CM Jr.Guided tissue regeneration(GTR)with bioabsorbable collagen membranes(CM)may generate more clinical attachment level gain than open flap debridement(OFD).J Evid Based Dent Pract,2014,14(1):22-24.
12姜元芹,郑建华,赖世佳.胶原膜支架植入联合鼻腔底黏骨膜瓣修补鼻中隔穿孔16例分析.临床军医杂志,2011,39(4):722-723.
13 Probst A,Aust D,Markl B,et al.Early esophageal cancer in Europe:endoscopic treatment by endoscopic submucosal dissection.Endoscopy,2015,47(2):113-121.
14 Choi JH,Kim ES,Lee YJ,et al.Comparison of quality of life and worry of cancer recurrence between endoscopic and surgical treatment for early gastric cancer.Gastrointest Endosc,2015,82(2):299-307.
15 Tanabe S,Ishido K,Higuchi K,et al.Long-term outcomes of endoscopic submucosal dissection for early gastric cancer:a retrospective comparison with conventional endoscopic resection in a single center.Gastric Cancer,2014,17(1):130-136.
16 Caga T,Gurer F.Polytetrafluoroethylene patch grafting for closure of stomach defects in the rat.Br J Surg,1993,80(8):1013-1014.
17 Ozlem N,Erdogan B,Gültekin S,et al.Repairing great duodenal defects in rabbits by e PTFE patch.Acta Chir Belg,1999,99(1):17-21.
18 Nikeghbalian S,Atefi S,Kazemi K,et al.Repairing large duodenal injuries in dogs by expanded polytetrafluoroethylene patch.J Surg Res,2008,144(1):17-21.
19 Oh DS,Manning MM,Emmanuel J,et al.Repair of full-thickness defects in alimentary tract wall with patches of expanded polytetrafluoroethylene.Ann Surg,2002,235(5):708-711.
20 de la Fuente SG,Gottfried MR,Lawson DC,et al.Evaluation of porcine-derived small intestine submucosa as a biodegradable graft for gastrointestinal healing.J Gastrointest Surg,2003,7(1):96-101.
21 Ueno T,de la Fuente SG,Abdel-Wahab OI,et al.Functional evaluation of the grafted wall with porcine-derived small intestinal submucosa(SIS)to a stomach defect in rats.Surgery,2007,142(3):376-383.
22 Takimoto K,Imai Y,Matsuyama K.Endoscopic tissue shielding method with polyglycolic acid sheets and fibrin glue to prevent delayed perforation after duodenal endoscopic submucosal dissection.Dig Endosc,2014,26(Suppl 2):46-49.
23 Han S,Chung H,Park JC,et al.Endoscopic management of gastrointestinal leaks and perforation with polyglycolic acid sheets.Clin Endosc,2017,50(3):293-296.
24 Jabaji Z,Brinkley GJ,Khalil HA,et al.Type I collagen as an extracellular matrix for the in vitro growth of human small intestinal epithelium.PLo S One,2014,9(9):e107814.
25刘文博.胶原蛋白类植入性医疗器械及其安全性评价探讨.国际生物医学工程杂志,2015,38(4):238-241,246.
26朱方强,陈民佳,朱明,等.炎症与组织再生修复.中华损伤与修复杂志(电子版),2017,12(1):72-76.
2 Iqbal CW,Cullinane DC,Schiller HJ,et al.Surgical management and outcomes of 165 colonoscopic perforations from a single institution.Arch Surg,2008,143(7):701-706.
3 van der Sluis FJ,Loffeld RJ,Engel AF.Outcome of surgery for colonoscopic perforation.Colorectal Dis,2012,14(4):e187-190.
4 Kume K.Endoscopic therapy for early gastric cancer:standard techniques and recent advances in ESD.World J Gastroenterol,2014,20(21):6425.
5 Verlaan T,Voermans RP,van Berge Henegouwen MI,et al.Endoscopic closure of acute perforations of the GI tract:a systematic review of the literature.Gastrointest Endosc,2015,82(4):618-628e5.
6 Spiliopoulos K,Markakis C,Tomos P,et al.Repair of gastric defects with an equine pericardial patch.Surg Today,2015,45(1):83-90.
7 Tanaka Y,Nakamura T,Fujii S,et al.Successful treatment of a perforated duodenal ulcer with polyglycolic acid sheets.Gastrointest Endosc,2017,85(6):1299-1300.
8 Tonai Y,Takeuchi Y,Akita H,et al.Iatrogenic duodenal perforation during underwater ampullectomy:endoscopic repair using polyglycolic acid sheets.Endoscopy,2016,48(S1):E97-98.
9 Sakaguchi Y,Tsuji Y,Yamamichi N,et al.Successful closure of a large perforation during colorectal endoscopic submucosal dissection by application of polyglycolic acid sheets and fibrin glue.Gastrointest Endosc,2016,84(2):374-375.
10 Qasim SB,Najeeb S,Delaine-Smith RM,et al.Potential of electrospun chitosan fibers as a surface layer in functionally graded GTR membrane for periodontal regeneration.Dent Mater,2017,33(1):71-83.
11 Faggion CM Jr.Guided tissue regeneration(GTR)with bioabsorbable collagen membranes(CM)may generate more clinical attachment level gain than open flap debridement(OFD).J Evid Based Dent Pract,2014,14(1):22-24.
12姜元芹,郑建华,赖世佳.胶原膜支架植入联合鼻腔底黏骨膜瓣修补鼻中隔穿孔16例分析.临床军医杂志,2011,39(4):722-723.
13 Probst A,Aust D,Markl B,et al.Early esophageal cancer in Europe:endoscopic treatment by endoscopic submucosal dissection.Endoscopy,2015,47(2):113-121.
14 Choi JH,Kim ES,Lee YJ,et al.Comparison of quality of life and worry of cancer recurrence between endoscopic and surgical treatment for early gastric cancer.Gastrointest Endosc,2015,82(2):299-307.
15 Tanabe S,Ishido K,Higuchi K,et al.Long-term outcomes of endoscopic submucosal dissection for early gastric cancer:a retrospective comparison with conventional endoscopic resection in a single center.Gastric Cancer,2014,17(1):130-136.
16 Caga T,Gurer F.Polytetrafluoroethylene patch grafting for closure of stomach defects in the rat.Br J Surg,1993,80(8):1013-1014.
17 Ozlem N,Erdogan B,Gültekin S,et al.Repairing great duodenal defects in rabbits by e PTFE patch.Acta Chir Belg,1999,99(1):17-21.
18 Nikeghbalian S,Atefi S,Kazemi K,et al.Repairing large duodenal injuries in dogs by expanded polytetrafluoroethylene patch.J Surg Res,2008,144(1):17-21.
19 Oh DS,Manning MM,Emmanuel J,et al.Repair of full-thickness defects in alimentary tract wall with patches of expanded polytetrafluoroethylene.Ann Surg,2002,235(5):708-711.
20 de la Fuente SG,Gottfried MR,Lawson DC,et al.Evaluation of porcine-derived small intestine submucosa as a biodegradable graft for gastrointestinal healing.J Gastrointest Surg,2003,7(1):96-101.
21 Ueno T,de la Fuente SG,Abdel-Wahab OI,et al.Functional evaluation of the grafted wall with porcine-derived small intestinal submucosa(SIS)to a stomach defect in rats.Surgery,2007,142(3):376-383.
22 Takimoto K,Imai Y,Matsuyama K.Endoscopic tissue shielding method with polyglycolic acid sheets and fibrin glue to prevent delayed perforation after duodenal endoscopic submucosal dissection.Dig Endosc,2014,26(Suppl 2):46-49.
23 Han S,Chung H,Park JC,et al.Endoscopic management of gastrointestinal leaks and perforation with polyglycolic acid sheets.Clin Endosc,2017,50(3):293-296.
24 Jabaji Z,Brinkley GJ,Khalil HA,et al.Type I collagen as an extracellular matrix for the in vitro growth of human small intestinal epithelium.PLo S One,2014,9(9):e107814.
25刘文博.胶原蛋白类植入性医疗器械及其安全性评价探讨.国际生物医学工程杂志,2015,38(4):238-241,246.
26朱方强,陈民佳,朱明,等.炎症与组织再生修复.中华损伤与修复杂志(电子版),2017,12(1):72-76.