可生物降解热敏性改性甲壳素水凝胶预防术后肠粘连效果的研究
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摘要
目的:探究可生物降解热敏性改性甲壳素凝胶在动物肠壁-腹壁损伤模型中预防术后肠粘连的效果。方法:首先在体外细胞实验中探究了凝胶的生物相容性。然后建立了新西兰兔盲肠侧壁-腹壁损伤肠粘连模型,对比了改性甲壳素凝胶和商用几丁糖凝胶预防术后粘连的效果。观察凝胶在体内的降解情况,以及凝胶是否会对主要器官产生毒性损害。结果:溶血试验中凝胶与生理盐水溶血程度无显著差别(P>0.05),表明凝胶不会溶血。细胞毒性试验发现,与凝胶直接接触肠上皮细胞的细胞活性与未接触凝胶的对照组无显著差异(P>0.05),表明凝胶不会对细胞生长增殖造成影响。动物实验中,两种凝胶减少了粘连形成,并且改性甲壳素凝胶还减小形成粘连的面积。结论:可生物降解热敏性改性甲壳素凝胶生物相容性良好,能减少术后肠粘连的发生,是一种具有潜在临床应用价值的防粘连屏障材料。
Objective:To investigate whether the injectable biodegradable thermosensitive in situforming chemically modified carboxymethyl chitin hydrogel can be used to prevent postoperative adhesion formation.Methods:We first confirmed biocompatibility of the hydrogel in vitro by using hemolysis assay and cell viability assay,then a postoperative adhesion rabbit model of sidewall defect-bowel abrasion was established and the anti-adhesion effect of the hydrogel comparing with another commercially available chitin hydrogel was evaluated in the animal model in vivo.Results:In vitro experiments,the hydrogel did not cause significant hemolysis,nor did it affect cell growth and proliferation,confirming the excellent biocompatibility of the hydrogel.In the in vivo experiment of animal model,we found that the hydrogel degraded completely 3 weeks after applied,and comparing with the commercially available chitin hydrogel,our hydrogel tended to be more effective in preventing postoperative adhesion formation,and it also reduced the area of the formed adhesion.Conclusion:The injectable biodegradable thermosensitive in-situ formingchemically modified carboxymethyl chitin hydrogel is a promising barrier system for prevention of postoperative adhesion.
Objective:To investigate whether the injectable biodegradable thermosensitive in situforming chemically modified carboxymethyl chitin hydrogel can be used to prevent postoperative adhesion formation.Methods:We first confirmed biocompatibility of the hydrogel in vitro by using hemolysis assay and cell viability assay,then a postoperative adhesion rabbit model of sidewall defect-bowel abrasion was established and the anti-adhesion effect of the hydrogel comparing with another commercially available chitin hydrogel was evaluated in the animal model in vivo.Results:In vitro experiments,the hydrogel did not cause significant hemolysis,nor did it affect cell growth and proliferation,confirming the excellent biocompatibility of the hydrogel.In the in vivo experiment of animal model,we found that the hydrogel degraded completely 3 weeks after applied,and comparing with the commercially available chitin hydrogel,our hydrogel tended to be more effective in preventing postoperative adhesion formation,and it also reduced the area of the formed adhesion.Conclusion:The injectable biodegradable thermosensitive in-situ formingchemically modified carboxymethyl chitin hydrogel is a promising barrier system for prevention of postoperative adhesion.
引文
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[2]Diamond MP.Incidence of postsurgical adhesions[M].New York:Springer,2000:217-220.
[3]李晓燕,冷金花.盆腹腔术后粘连的发生机制及预防措施[J].中国微创外科杂志,2012,12(2):124-128.Li X,Leng J.Postoperative adhesion after abdomon and pelvis surgery:mechanism and prevention[J].Chinese Journal of Minimally Invasive Surgery,2012,12(2):124-128.
[4]张正.PCLA-PEG-PCLA温致水凝胶的合成、多肽包裹与修饰及其医学应用[D].上海:复旦大学,2011.Zhang Z.Synthesis of biodegradable thermosensitive PCLA-PEG-PCLA hydrogels,encapsulation of or modified by peptides,and potential medical applications[D].Shanghai:Fudan University,2011.
[5]莫利锋.可生物降解和热敏性的单甲氧基聚乙二醇—聚乳酸(MPEG-PLA)水凝胶对预防术后腹腔粘连的作用研究[D].泸州:四川医科大学,2015.Mo L.Biodegradable and thermosensitive monomethoxy poly(ethylene glygol)-poly(lactic acid)hydrogel as a barrier for prevention of post-operative abdominal adhesion[D].Luzhou:Sichuan Medical University,2015.
[6]王德娟,莫家骢,潘仕荣,等.羧甲基壳聚糖预防大鼠术后腹膜粘连的研究[J].中山大学学报:医学科学版,2008,29(3):287-293.Wang D,Mo J,Pen S,et al.Efficacy of carboxymethyl chitosan on prevention experimental postoperative peritoneal adhesions and histologic studies[J].Journal of Sun Yat-Sen University:Medical Sciences,2008,29(3):287-293.
[7]任常.液态和隔膜防粘连材料防止兔子宫术后盆腔粘连的基础研究[D].北京:北京协和医学院,2011.Ren C.Liquid and barrier anti-adhesive materials for reducing pelvic adhesions in a rabbit double uterine horn model:a basic research[D].Beijing:Peking Union Medical College,2011.
[8]Zhang Z,Ni J,Chen L,et al.Biodegradable and thermoreversible PCLA-PEG-PCLA hydrogel as a barrier for prevention of post-operative adhesion[J].Biomaterials,2011,32(21):4 725-4 736.
[9]Yu L,Hu H,Chen L,et al.Comparative studies of thermogels in preventing post-operative adhesions and corresponding mechanisms[J].Biomaterials Science,2014,2(8):1 100-1 109.
[10]Yeo Y,Kohane DS.Polymers in the prevention of peritoneal adhesions[J].European Journal of Pharmaceutics and Biopharmaceutics,2008,68(1):57-66.