医用化学组织粘合剂用于角巩膜全层裂伤治疗的实验研究
详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文
摘要
氰基丙烯酸酯(CA)是具有胶接功能、力学功能和生物医学功能的医用化学组织粘合剂。当暴露于水或血液时,迅速发生聚合反应,能在瞬间发挥其强粘接作用。随着医用化学组织粘合剂合成方法和技术改进,α-氰基丙烯酸正辛酯为主体的胶粘剂得到了迅速发展,具有组织相适应的物理性能、稳定的化学性能、良好的生物相容性,已在普外、胸外、脑外、妇产科、五官科、美容整形等专业学科进行了临床应用,并取得了较好的疗效。
     化学医用组织粘合剂因其使用方便、快捷、安全、价廉,已被用于眼科治疗角膜溃疡、眼外肌矫正斜视手术、义眼台植入术、泪囊鼻腔吻合术和眼睑成形术等动物实验或临床研究。但对其用于有张力的角膜和巩膜全层裂伤的治疗尚未见报道。
     本课题拟研究化学组织粘合剂粘合角膜全层裂伤的可行性,并评价其对眼表组织的生物相容性,在此基础上探讨化学组织粘合剂应用于粘合巩膜全层裂伤的可行性。本研究为化学组织粘合剂在眼科的应用提供了实验基础,也为眼科手术的进步和新手术的开展提供了新的思路。组织粘合剂在眼科将具有广阔的应用前景。
     第一部分医用化学组织粘合剂眼表应用的组织相容性及用于角膜全层裂伤治疗的研究
     目的:研究CA应用于眼表对眼组织的生物相容性,并在此基础上探讨治疗角膜全层裂伤的可能行。
     方法:
     1、日本大耳白兔45只,随机分5组。
     2、左眼为缝线组,右眼为CA组,术后3、7、14、30、90天大体观察后,按照科学实验动物的道德条例静脉注射空气处死动物,取眼球和角膜行实验指标的观测。
     3、术后于观察时间点裂隙灯下观察两组实验兔角膜伤口密闭性、角膜混浊程度、角膜新生血管、CA的降解和前房情况;并行房水行蛋白含量测定、角膜内皮细胞共聚焦显微镜检查、眼球抗球内压力测定、光镜观察、电镜观察。
     结果:
     1、CA组所用手术时间少于缝合组,两组有显著性差异。
     2、两组实验兔在术后3天,均可见部分兔眼角膜混浊。术后7天CA组与缝线组兔眼角膜均出现新生血管,CA组较缝线组严重,术后30天缝线组大部分消退,CA组角膜均残留2-3支新生血管。术后90两组新生血管基本吸收,胶块脱落,角膜伤口均可看见线状白斑。
     3、缝线组与CA组术后各时间点房水蛋白含量测定和角膜内皮细胞共聚焦显微镜检查均未见明显差异。眼球抗球内压力在术后3天高于正常眼压,并随着角膜伤口的愈合,抗眼球内压力逐渐升高,且缝线组和CA组无显著差异。
     4、光镜示缝线组术后早期角膜伤口炎细胞浸润,角膜上皮细胞植入;CA组术后早期炎细胞浸润不明显,无角膜上皮植入。术后30天两组角膜伤口成纤维母细胞和炎细胞均明显减少,纤维细胞增多。术后90天两组伤口组织均愈合。电镜观察,CA组和缝线组角膜内皮超微结构未见明显差异。
     结论:
     1、CA具有较好的组织相容性,用于眼表不引起眼组织的毒性及病理学改变。
     2、CA能在术中迅速闭合角膜全层裂伤伤口,并产生足够的抗张能力,支持伤口愈合。
     3、CA可能引起角膜伤口愈合时角膜新生血管,但随伤口愈合,角膜新生血管完全消退。
     4、CA粘合角膜伤口方便、快捷、经济,并能避免缝线医源性二次损伤。
     第二部分医用化学组织粘合剂用于巩膜全层裂伤治疗的研究
     目的:研究CA粘合巩膜全层裂伤伤口组织愈合过程,并与医用缝线缝合方法比较,评价CA治疗巩膜全层裂伤的可行性。
     方法:
     1、日本大耳白兔45只,随机分5组。
     2、左眼为缝线组,右眼为CA组,术后3、7、14、30、90天大体观察后,按照科学实验动物的道德条例静脉注射空气处死动物,取眼球和巩膜行实验指标的观测。
     3、术后于各观察时间点裂隙灯下观察两组实验兔巩膜伤口密闭性、结膜充血情况、眼前后节情况,并测量眼球抗球内压力,行光镜、电镜观察伤口组织愈合过程。
     结果:
     1、CA组所用手术时间少于缝线组,两组有显著性差异。
     2、CA组和缝线组在各观察点伤口均闭合,未见眼前、后节炎性反应;两组睑球结膜充血无明显差异。
     3、CA组和缝线组眼球抗球内压力在术后3天大于正常眼压,并随着巩膜伤口的愈合,抗眼球内压力逐渐升高,缝线组和CA组无显著差异。
     4、光镜示CA组术后早期巩膜伤口组织成纤维细胞从巩膜内层向外层愈合,缝线组成纤维细胞从外层向内层愈合,术后30天两组巩膜伤口成纤维母细胞和炎细胞均明显减少,纤维细胞增多。术后90天两组伤口组织均愈合。CA组未引起视网膜及脉络膜的异常改变。电镜观察,CA组和缝线组巩膜超微结构未见明显差异。
     结论:
     1、CA能在术中迅速闭合巩膜全层裂伤伤口,并产生足够的抗张力,支持伤口愈合。
     2、CA用于修复巩膜全层裂伤伤口,具有较好的组织相容性,不引起巩膜的毒性及病理学改变。
     3、CA粘合巩膜伤口愈合与缝线法有差异,但不影响伤口愈合的速度和抗张力。
     4、CA粘合巩膜伤口方便、快捷、经济,并能避免缝线医源性二次损伤。
Background and Aims 2-Octyl Cyanoacrylate is a kind of chemical tissue adhesive, it have many functions in adhesive capacity, mechanics and biology. When exposed to water or blood, it can have powerful adhesion instantly. With the technical advancement of tissue adhesive, the adhesive used by 2-Octyl Cyanoacrylate have been devlopped quickly.Because its nice biocompatibility, it hve been many successful clinical applications in forensic sursery, brain sursery, aural sursery, gynaecology and obstetrics, facial organs, plastic surgery and etc.
     Because the tissue adhesive is convenient, quick, safe and inexpensive than others, it has been used in helcoma, strabotomy, anophthalmic cavity reconstruction, and so on. However, no article is showed that the tissue adhesive has been used in corneal and sclerotic chapped pentrating wounds.
     The experimental study investigated the feasibility of agglutinating corneal and sclerotic chapped pentrating wound with the tisuue adhesive, and evaluated the biocompatibility to ocular surface. Based on these facts, we study the effect of agglutinating corneal and sclerotic chapped pentrating wound. Our study provided experiment foundation for tissue adhesive to apply in ophthalmology, and a new idea of progress in ophthalmology operation and new surgery carried out. The tissue adhesive will have wide prospect in ophthalmology in the future.
     Part 1 the experimental study on the histocompatibility of tissue adhesive and application for corneal chapped petrating wound
     Objective: To investigate the biocompatibility to ocular surface with CA and the application for corneal chapped petrating wound.
     Methods:
     1. 45 Japanese white rabbits are random divided 5 groups. Each groups had 9 rabbits.
     2. all the rabbits’s left eyes are sutural group, Right eyes are CA group. On days 3, 7, 14, 30, 90 after surgery operation, rabbits are executed by mainline, then take their eyeballs and corneas to observe the experimental targets.
     3. on the time after operation, we observe the two groups of corneal wound, nubecula, new blood vessels of cornea, anterior chamber, degradation of CA, protein content of aqueous humor, corneal endothelial cell by Microscope, tension of eyeball, light microscope, transmission electron microscope.
     Results:
     1. Surgury time of CA group less than sutural group.
     2. On day 3 after operation, two groups have part of corneal turbidity.on day 7, new blood vessels of CA group more than sutural group. On day 30, the vessels of sutural group are disappeared, CA group have 2-3 blood vessels. On day 90, all of blood vessels have been absorbed, CA have fall out, sutural group have been seen white sutural trail.
     3. After operation, no difference has been observed with two groups by protein content of aqueous humor and corneal endothelial cell by Microscope. On each observing point, tension of two groups’eyeball more than the normal, and the tension increase gradually with increasing time after surgery.
     4. Forepart after surgery operation, by light microscope, corneal wound of sutural group have inflammatory cell infiltration and corneal epithelium implantation; corneal wound of CA group have infalmmatory cell infiltration a little, and no corneal epithelium implantation. on day 30, fibroblasts and inflammatory cells of two groups decrease distinctly, and fiber cells increase. On day 90, the wound of two groups cicatrize fully. By transmission electron microscope, the ultrastructures of corneal endothelial cells have no difference between the two groups.
     Conclusion:
     1. CA has better biocompatibility to ocular surface, and don’t bring toxicity to eyes and no pathology change.
     2. CA can quickly close corneal chapped petrating wound, and bring enough tensile force that sustain the wound to close.
     3. When corneal wound closing with CA, cornea can make some new blood vessels. But with the wound closed, the vessels disappeared completely.
     4. CA can agglutinate the corneal wound conveniently, quickly, economically, and avoid the hypo-damnify because of sutural operation.
     Part 2 the experimental study on the application for corneal chapped petrating wound
     Objective: To compare that CA treat the sclerotic chapped pentrating wound with sutural operation, investigate the feasibility of application with CA.
     Methods:
     1. 45 Japanese white rabbits are random divided 5 groups. Each groups had 9 rabbits.
     2. All the rabbits’s left eyes are sutural group, Right eyes are CA group. On days 3, 7, 14, 30, 90 after surgery operation, rabbits are executed by mainline, then take their eyeballs to observe the experimental targets.
     3. On the time after operation, we observe the two groups of sclerotic wound, conjunctiva injection, ocular protomerite and deutomerite, operation time, tension of eyeball, light microscope, transmission electron microscope.
     Results:
     1. Surgury time of CA group is less than sutural group.
     2. On each time after operation, two groups have no inflammation in ocular protomerite and deutomerite, and no difference on the conjunctiva injection.
     3. Each observing point after operation, tension of two groups’eyeball more than the normal, and the tension increase gradually with increasing time after surgery.
     4. Forepart after surgery operation, by light microscope, CA group mechanocyte of sclerotic wound close from inside to outside. Sutural group is contrary. On day 30, fibroblasts and inflammatory cells of two groups decrease distinctly, and fiber cells increase. On day 90, the wound of two groups cicatrize fully. By transmission electron microscope, sclerotic endothelial cells of two groups have no difference.
     Conclusion:
     1. CA can quickly close sclerotic chapped petrating wound, and bring enough tensile force that sustain the wound to close.
     2. CA has better histocompatibility with sclerotic wound, and don’t bring toxicity to sclera andretina. CA doesn’t bring pathology change.
     3. On forepart the phenomenon that CA treat sclerotic wound is different with suture treating, but these don’t affect the rate of wound close.
     4. CA can agglutinate the sclerotic wound conveniently, quickly, economically, and avoid the hypo-damnify because of sutural operation.
引文
1. David C. Ritterband, MD, Seth W. Meskin, MD. Laboratory Model of Tissue Adhesive (2-Octyl Cyanoacrylate) in Sealing Clear Corneal Cataract Wounds. Ophthalmology, 2005 Nov;112(11) :2015-2021.
    2.熊建义,刘建军.医用胶粘剂主体材料α-氰基丙烯酸正辛酯的合成研究.湘潭大学自然科学学报, 2005; 2:102-103.
    3. Gloria Y. S. Leung, MRCS. Preliminary In Vitro Evaluation of 2-Octyl Cyanoacrylate (Dermabond_) to Seal Corneal Incisions. Cornea, 2005;24:998–999.
    4. Toriumi DM, Raslan WF, Friedman M, Tardy ME .Histotoxicity of cyanoacrylate tissue adhesives. A comparative study. Arch Otolaryngol Head Neck Surg, 1990 May;116(5):546-50.
    5. Meskin SW, Ritterband DC. Liquid bandage (2-octyl cyanoacrylate) as a temporary wound barrier in clear corneal cataract surgery. Ophthalmology, 2005 Nov;112(11): 2015-21.
    6.侯振江.房水实验室检查的临床意义.中国实用眼科杂志,1997;15(3) :137-140.
    7.董冰松.兔角膜承受内压力及角膜组织化学的实验研究.眼外伤职业眼病杂志, 1999; 21(2) :86-88.
    8.秦应祥,赵敏.组织粘合剂在眼科中的应用.国际眼科杂志, 2004;4(4) :690-694.
    9. Tonelli E Jr, de Almeida HC, Bambirra EA. Tissue adhesives for a sutureless fadenoperation: an experimental study in a rabbit model. Invest Ophthalmol Vis Sci, 2004 Dec;45(12):4340-5.
    10.夏穗生,田霞.新一代喷涂型福爱乐医用胶(基础研究).临床外科杂志, 2003; 11(2) :120-121.
    11. Ollivier F, Delverdier M, Regnier A. Tolerance of the rabbit cornea to an n-butyl-ester cyanoacrylate adhesive (Vetbond). Vet Ophthalmol,2001;4(4):261-6.
    12.刘祖国.眼表疾病学.人民卫生出版社, 2003;174.
    13.李凤鸣.中华眼科学.北京:人民卫生出版社, 2005;214.
    14. Vote BJ, Elder MJ. Cyanoacrylate glue for corneal perforations: a description of a surgical technique and a review of the literature. Clin Experiment Ophthalmol, 2000 Dec;28(6):437-42.
    15. Francisco Cláudio Dantas Mota1, Duvaldo Eurides1, Patricia Maria Coletto Freitas1. Use of the n-butyl cyanoacrylate adhesive and the polyglactine thread suture for corneal rhaphy in rabbit (Oryctolagus cunicullus) .Journal Of Veterinary Science, 2004;5(3) :267–270.
    16.陈家祺.血管内皮生长因子及其受体在角膜的表达和临床意义的探讨.眼科学报, 2002;18(4) :203-207.
    17. Tetsuo Hida,Sherif M. Retinal toxicity of cyanoacrylate tissue adhesive in the rabbit. Retina, 1988;8:148-153.
    1.秦应祥.组织粘合剂在眼科的应用.国际眼科杂志, 2004;4(4):690-694.
    2. Chan, Stanley M; Boisjoly, Hélène. Advances in the use of adhesives in ophthalmology. Curr Opin Ophthalmol, 2004 Aug;15(4):305-10.
    3. Bloomfield, S., A. H. Bamet, and P. D. Kanter. The use of Eastman 910 monomer as an adhesive in ocular surgery, I, biologic effects on ocular tissues. Am. J. Ophth., 1963;55:742-8,.
    4. Bloomfield, S., A. H. Barnet, and P. D. Kanter. The use of Eastman 910 monomer as an adhesive in ocular surgery, II, effectiveness in closure of limbal wounds in rabbits. Am. J. Ophth, 55:5, 1963.
    5. Macsai MS. The management of corneal trauma: advances in the past twenty-five years. Cornea, 2000 Sep;19(5):617-24.
    6. Chen, Wei-Li, Lin, Chung-Tien. Comparison of the Bacteriostatic Effects, Corneal Cytotoxicity, and the Ability to Seal Corneal Incisions Among Three Different Tissue Adhesives. Cornea, 2007 Dec;26(10):1228-1234.
    7. Roberta Pereira de Almeida Manzano, Sandra Cayres Naufal. Antibacterial Analysis In Vitro of Ethyl-cyanoacrylate Against Ocular Pathogens. Cornea, 2006 Apr;25(3):350-351.
    8. Leung GY, Peponis V. Preliminary in vitro evaluation of 2-octyl cyanoacrylate (Dermabond) to seal corneal incisions. Cornea, 2005 Nov;24(8):998-9.
    9. Meskin SW, Ritterband DC. Liquid bandage (2-octyl cyanoacrylate) as a temporary wound barrier in clear corneal cataract surgery. Ophthalmology, 2005 Nov;112(11): 2015-21.
    10. McKinley SH, Yen MT. Octyl-2-cyanoacrylate tissue adhesive in external dacryocystorhinostomy. Ophthal Plast Reconstr Surg, 2005 May;21(3):197-200.
    11. Naruse S, Mori K. A new technique for removing the inner wall of Schlemm's canal using cyanoacrylate, 2003 Apr;81(2):151-4.
    12. Ricci B, Ricci F. Octyl 2-cyanoacrylate in sutureless surgery of extraocular muscles: an experimental study in the rabbit model. Graefes Arch Clin Exp Ophthalmol, 2000 May;238(5):454-8.
    13. Lucieni Cristina Barbarini Ferraz. 2-octyl-cyanoacrylate in rabbit anophthalmic cavity reconstruction. Ophthal Plast Reconstr Surg. Arq. Bras, 2007 Mar;70(2):264-9.
    14. Donnenfeld ED, Perry HD. Cyanoacrylate temporary tarsorrhaphy in the management of corneal epithelial defects, 1991 Oct;22(10):591-3.
    15. Shepler TR, Seiff SR. Use of isobutyl cyanoacrylate tissue adhesive to stabilize external eyelid weights in temporary treatment of facial palsies. Ophthal Plast Reconstr Surg, 2001 May;17(3):169-73.
    16. Greene D, Koch RJ, Goode RL. Efficacy of octyl-2-cyanoacrylate tissue glue in blepharoplasty. A prospective controlled study of wound-healing characteristics. Arch Facial Plast Surg ,1999;1 (4):292–296.
    17. Donnenfeld ED, Perry HD, Nelson DB. Cyanoacrylate temporary tarsorrhaphy in the management of corneal epithelial defects. Ophthalmic Surg, 1991 Oct;22(10):591-3.
    18. L. Masetti, E. Bellei. Use of Glubran 2 in Ophthalmic Surgery: A Preliminary Study. Veterinary Research Communication, 2007;31 (1):305–307.
    19. Jorge L, M. Emilia Mulet. Evaluation of a New Bioadhesive Copolymer (ADAL_) to Seal Corneal Incisions. Cornea, 2004 Mar;23(2):180-189.
    20. Duffy MT,Bloom JN. Sutureless ophthalmic surgery: a scaffold-enhanced bioadhesive technique. J AAPOS, 2005 Aug;9(4):315-20.
    21. Johann M. G. Reyes, Samantha Herretes. A Modified Chondroitin Sulfate Aldehyde Adhesive for Sealing Corneal Incisions. IOVS, 2005 Apr;46(4):1247-1250.
    22. Miki D, Dastgheib K. A photopolymerized sealant for corneal lacerations. Cornea, 2002 May;21(4):393-399.

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700