缓释胶原在豚鼠听泡内的降解过程及其生物相容性

Degradation of collagen in acoustic vesicles of guinea pigs and its biocompatibility

目的:观察可降解的胶原基材料在豚鼠听泡内的降解过程及其生物相容性情况。方法:实验于2005-03/05在解放军海军总医院完成。选取白豚鼠20只,随机分为5组:假手术组、胶原基植入1,2,3,4周组,4只/组。全部白豚鼠腹腔麻醉后,无菌条件下取左侧耳后切口,打开听泡。除假手术组外,其余各组均植入BME-10X医用胶原膜,缝合手术切口,待豚鼠全麻清醒后观察其行为学变化。胶原基植入1,2,3,4周组分别于胶原基植入1,2,3,4周时,麻醉后在手术显微镜下打开听泡,观察胶原材料的大体变化。处死动物,取其左侧听泡,切片苏木精-伊红染色后对胶原基材料在听泡内的降解及生物相容性进行观察。结果:实验选用白豚鼠20只,全部进入结果分析。①胶原基材料植入后各组动物行为学观察结果:各组动物全麻后均清醒,未出现死亡。胶原基材料植入后未出现瘫痪、抽搐、呕吐、尿便失禁、原地打转等不良反应,行为活跃,反应敏捷。②各组胶原基材料在听泡内降解及生物相容性的大体观察:胶原基植入1周组植入的胶原材料大致保持了植入前形状,无新生血管长入,听泡内黏膜无明显新生血管增生;胶原基植入2,3周组无肉眼可见的新生组织及血管长入;胶原基植入4周组听泡内的胶原材料已完全溶解吸收,听泡内无新生纤维组织条索,无积液。③各组胶原基材料在听泡内降解及生物相容性的病理检查:胶原基植入1周组可见少量淋巴细胞浸润,未见异物巨细胞,听泡内黏膜无肉芽组织增生;胶原基植入2周组的淋巴细胞浸润继续减轻;至胶原基植入3周组仅见少量淋巴细胞。结论:随着植入时间的延长,胶原材料在豚鼠听泡内逐渐被降解吸收,周围黏膜无结节和肉芽组织形成。提示可降解的胶原基材料具有良好的生物相容性,可以做为中耳控释给药的载体材料。

AIM： To observe the degradation of the collagen material and its biocompatible in acoustic vesicles of guinea-pigs. METHODS： The study was conducted in Navy General Hospital of Chinese PLA from March to May 2005. Twenty white guinea pigs were selected and divided into 5 groups randomly, which were feigned operation group and collagen implantation 1, 2, 3, 4-week groups with 4 animals in each group. All animals were general anaesthesia through abdomen cavity. Their acoustic vesicles were open through retroauricular sterile incision. BME-10X collagen membrane was implanted into every acoustic vesicle except these in the feigned operation group. The incision was closed, and the changes of praxiology of the animal action were observed after wakefulness. After 1, 2, 3, 4 weeks, the guinea-pigs were given general anaesthesia, the acoustic vesicles were opened again to observe the changes of the collagen membrane, then the animals were killed, the left acoustic vesicles were sliced to observe the degradation of collagen membrane and biocompitable with hematoxylin-eosin staining RESULTS： All the 20 experimental white guinea pig animals were involved in the result analysis. ①Observational result of animal ethology of every group after the collagen membrane implanted： All animals waked up after anaesthesia, no death. No animal paralyzed, twitched, vomited, incontinence of urine and feces or rotated, etc. The actions of the animals were active, and the response of the animals was agile. ②General observation of the degradation and biocompatible in the acoustic vesicles of guinea pigs： The collagen material was keeping its original shape after 1- week implantation and no neo-vessel grown into. Also, no neo-vessel was observed in the collagen material in auditory vesticle. No new tissue and vessel in the 2, 3-week group. In the 4-week group, the collagen material was dissolved and absorbed, there weren＇t any neo-tissue grown or liquid existed.③Pathology examination on degradation and biocompatible of the collagen material in acoustic vesicles： There were some lymphocytes in collagen material in 1-week group, no foreign body giant cells. No granulation tissue grew in the acoustic vesicles; the lymphocytes were decreased in the 2-week group, and there were only a few lymphocytes in collagen material in the 3-week group. CONCLUSION： The collagen material is degraded and absorbed slowly along with the horary extension, and the vesicle membrane is normal, no node or granulation tissue forming. It indicates that the degradable collagen material has good biocompatibility, and can be used for controlled drugrelease carrier in middle ear.