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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

The Experimental Study on Tissue Adhesive Application for Corneal and Sclerotic Pentrating Wounds

【作者】 王蕊

【导师】 王一;

【作者基本信息】 第三军医大学 , 眼科学, 2008, 硕士

【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。

【Abstract】 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 woundObjective: 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 woundObjective: 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.

【关键词】 a-氰基丙烯酸正辛酯缝线巩膜角膜伤口
【Key words】 rabbit2-octyl Cyanoacrylatesuturescleracorneawound
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