Effect of Chitosan-Trimer on the Prevention of Postoperative Intraperitoneal Adhesion Formation in Rats

랫트에서 Chitosan-Trimer가 복강유착에 미치는 영향

  • Kwon, Eun-ju (College of Veterinary Medicine, Kyungpook National University) ;
  • Jang, Kwang-ho (College of Veterinary Medicine, Kyungpook National University) ;
  • Jang, In-ho (College of Veterinary Medicine, Kyungpook National University)
  • Published : 2001.09.01

Abstract

This study was performed to investigate the effects of chitosan-trimer (CT) on the prevention of postoperative adhesion formation in the rate model. All animals divided into PBS (control), 1% CT, 3% CT, and chitin treated group. The mean adhesion score in 1% CT group (1.03$\pm$0.63), 3% CT group (0.64$\pm$0.53) and chitin group (1.67$\pm$0.71) was found to be lower than that in control group (2.07$\pm$0.81). More favorable adhesion prevention was achieved in 3% CT group (0.64$\pm$0.53) in comparison with the control group, 1% CT group, and chitin group without any hemorrhagic complications. A statistically significant difference was observed in adhesion formation between control group and 3% CT group (p<0.001). In control group, 44 of 45 sites (97.7%) formed adhesions between the intestine defects. In contrast, 3% CT was effective in reducing the incidence of adhesion formation to 17 to 45 sites (62.2%) (p<0.05). The locations of adhesions were observed in serosa-serosa (60%), serosa-mesentery (13.3%), serosa-connective tissue of testis (10%), omentum-liver (10%), serosa-omentum (3.3%), serosa-cecum (3.3%), and serosa-incision (0%). On the results of histological analysis, grade of inflammation and fibrosis at the sites of postoperative peritoneal adhesion formation were not significantly different in all groups. But, 3% CT showed the lowest score of inflammation and fibrosis. In 3% CT group, the rate of increase of plasma fibrinogen was significantly lower compared with that in control group from pre-operation to 10 days later (p<0.05). There were no appreciable difference in the CBC, leukocyte differential counts and total protein concentrations among four groups. In conclusion, our data suggested that CT should be effective on reducing adhesion formation in experimental rat models. The results also showed that 3% CT does not adversely affect normal wound healing and healthy recovery after operation.

복강 내 유착은 단층편평상피로 구성된 복막의 손상으로 장막표면의 염증반응을 일으켜 창상조직의 혈관투과성이 증가하여 많은 장액성 혈액삼출물이 생산되고, 이 혈액삼출물내의 fibrin이 제거되지 않으면 초기섬유소성 유착이 발생한다. 따라서 유착방지는 섬유소성 부착물의 정상적인 용해를 방해하는 인자들과 관계가 있다. Chitosan은 poly-$\beta$(1$\longrightarrow$4)-D-glucosamine으로 chitin을 탈아세틸화시킨 것으로 복강유착방지에 효과가 있다고 알려진 Hyaluronic acid(HA)와 구조상 유사성을 가지고 있다. 본 연구는 쥐에서 회장에 유착을 유도한 후 PBS (control group), 1% Chitosan Trimer (CT, 1% CT group), 3% CT (3% group), chitin (chitin group)을 복강내 주입하여서 10일 뒤에 유착방지효과, 유착발생정도, 조직검사, 혈액상의 변화를 관찰하였다. 총백혈구수, 총적혈구수, PCV, PLT, Total protein은 전군에서 유의적인 변화가 나타나지 않았다. 조직검사상에서 유의적인 차이는 나타나지 않았으나, 3% CT군은 다른 군에 비해 Fibrosis와 염증반응정도에 대한 점수가 낮았다. 혈장섬유소원은 전군에서 수술 후 증가하였으나 3% CT군은 대조군에 비해 증가율이 낮아서 유의적인 차이를 보였다 (p<0.05). 유착장소는 전군에서 장막-장막 (60%), 장막-장간막 (13.3%), 장막-고환쪽 결합조직 (10%), 대망-간 (10%), 장막-대망 (3.3%), 장막-맹장3 (3.3%)순으로 발생하였다. 유착발생빈도는 3% CT군이 62.2% 로 대조군 97.7%, 1% CT군 81.8%, chitin군 93.3%에 비해 유의적으로 낮았다 (p<0.05). 유착 형성은 대조군, 1% CT, 3% CT 및 chitin 투여군에서 각각 2.07$\pm$0.81, 1.03$\pm$0.63, 0.64$\pm$0.53 및 1.67$\pm$0.71로 3% CT군은 대조군에 비해 유의적인 감소를 보였다 (p<0.001).

Keywords

References

  1. Surgery v.125 Surgical stress and the small intestine: Role of oxygen free radicals Anup R;Apama V;Pulimood A;Balasubramanian KA
  2. J Am Coll Surg v.183 Prevention of postoperative abdominal by a sodium hyaluronate-based bioresorbable membrane Becker JM;Dayton MT;Fazio VW
  3. Biochem J v.239 Increased hyaluronate synthesis is required for fibroblast detachment and mitosis Brecht M;Mayer U;Schlosser E;Prehm P
  4. J Surg Res v.20 A unifying pathogenetic mechanism in the etiology of intraperitoneal adhesions Buckman RF;Woods M;Sargent L;Gervin AS
  5. Fertil Steril v.66 A hyaluronate based gel for the prevention of postsurgical adhesions:evaluation in two animal species Burns JW;Burgess L;Skinner K;Rose R;Colt MJ;Diamond MP
  6. Surgery v.121 Prevention of postoperative adhesions with N,O-carboxymethyl chitosan: examination of the most efficacious preparation and the effect of N,O-carboxyethyl chitosan on postsurgical healing Costain DJ;Kennedy R;Ciona C;McAlister VC;Lee TDG
  7. Textbook of small animal surgery(2nd ed.) Peritoneum and peritoneal cavity Crowe DT;Bjorling DE
  8. Surg Gyne & Obstet v.133 The cause and prevention of postoperative intraperitioneal adhesions Ellis H
  9. Fertil Steil v.70 A barrier composed of chemical cross-linked hyaluronic acid (Incert) reduces postoperative adhesion formation Haney AF;Doty E
  10. Ferti Steril v.74 Use of fibrionlytic agents in the prevention of postoperative adhesion formation Hellebrekers BWJ;Trimbos-Kemper TCM;Trimbos JBMZ;Emeis JJ;Kooistra T
  11. Surgery v.125 Prevention of adhesion formation with use of sodium hyaluronate-based bioresorbable membrane in a rat model of ventral hernia repair with polypropylene mesh-a randomized. controlled study Hooker GD;Taylor BM;Driman DK
  12. Surgery v.94 A comparison of prosthetic materials used to repair abdominal wall difects Jenkins SD;Klamer TW;Parteka JJ;Condon RE
  13. Fertil Steril v.68 Reduction of adhesion formation by postoperative administration of ionically cross-linked hyaluronic acid Johns DS;Kiorpes TC;Rodgers KE;DiZerega GS;Donahue WD
  14. Korean J Vet Clin Med v.9 Study on adhesion formation by artificial injuries in rats Kang TY;Choi MC;Lee HJ
  15. Surgery v.120 Prevention of experimental postoperative peritoneal adhesions by N,O-carboxymethyl chitosan Kennedy R;Costain DJ;McAlister VC;Lee TDG
  16. Surgery v.109 Beneficial actions of exogenous hyaluronic acid on wound healing King SR;Hickerson WL;Proctor KG
  17. Spine v.16 Vrscous carboxymethylcellulose in the prevention of epidural scar formation Kitano T;Zerwekh JE;Edwards ML;UsuiYand Allen MD
  18. J Periodontol v.67 Osteogenesis enhenced by chitosan (poly-N-acetyl glucosaminoglycan) in vitro Klokkevold PR;Vandemark L;Kenney EB;Bernard GW
  19. Fertil Steril v.72 Reduction of adhesion formation with cross-linked hyaluronic acid after peritoneal surgery in rats Kocak I;Unlu C;Akcan Y;Yakin K
  20. J Invest Surg v.11 An inhibitor of cell proliferation associated carboxymethyl chitosan Krause TJ;Goldsmith NK;Ebner S;Zazanis GA;Mckinnon RD
  21. Fertil Steril v.69 Reduction of postsurgical adhesion formation in the rabbit uterine horn model with use of hyaluronate/carboxymethylcellulose gel Leach RE;Burns JW;Dawe EJ;SmithBarbour MD;Diamond MP
  22. Am J Surg v.165 Role of Mast Cells in Peritoneal Adhesion Formation Liebman SM;Langer JC;Marshall JS;Collins SM
  23. Br J Surg v.61 Observations on the pathogenesis of peritoneal adhesions: a light and electron microscopical study Milligan DW;Raftery AT
  24. J Thorac Cardiovasc Surg v.107 Prevention of postoperative peritioneal adhesions with a hyaluranic acid coation solution Mitchell JD;Lee R;Hodakowski GT;Neya K;Harringer W;Valeri R;Vlahakes GJ
  25. Am J Obstet Gynecol v.165 The ability of recombinant tissue plasminogen activator to inhibit post-radical pelvic surgery adhesions in the dog model Montz FJ;Fowler JM;Wolff AJ;Lacey SM;Mohler M
  26. J Vet Med Sci v.57 Evaluation of chitin and chitosan on open wound healing in dogs Okamto Y;Shibazaki K;Minami S;Matsuhashi A;Tanioka S;Shigemasa Y
  27. J Int Med Res v.27 The effect of cross-linked hyaluronate hydrogel on the reduction of post-surgical adhesion reformation in rabbits Osada H;Takahashi K;Fujii TK;Tsunoda I;Satoh K
  28. Br J Surg v.76 Reduced human peritoneal plasminogen activating activity: possible mechanism of adhesion formation Thompson JM;Paterson-Brown S;Harbourne T;Whawell SA;Kalodiki E;Dudley HA
  29. Fertil Steril v.56 Effect of hyaluronic acid on postoperative intraperitioneal adhesion formation and reformation in the rat model Urman B;Gomel V
  30. Lancet v.335 Peritoneal firinolytic activity and intra-abdominal adhesions Vipond MN;Whawell SA;Thompson JN;Dudley HAF