摘要
目的:将雷帕霉素溶于药用蓖麻油中制成滴眼剂,观察雷帕霉素滴眼剂对大鼠角膜的毒性作用,了解其用药安全性及适宜剂量,为雷帕霉素滴眼剂在角膜移植中的应用奠定基础。方法:实验于2006-06/10在南方医科大学珠江医院中心实验室完成。选用SD大鼠15只,按随机数字表法分为5组,即生理盐水组、蓖麻油滴眼组、5g/L,10g/L及20g/L雷帕霉素滴眼组,每组3只。适应性培养1周后开始实验。各组大鼠均双眼用药,分别滴用不同滴眼剂,6次/d,1滴/次,连续7d。每日对大鼠角膜行裂隙灯显微镜检查并进行临床分级,0级:角膜透明无水肿,光源镜面反射清晰;1级:角膜透明度稍低,镜面反射像边界尚清。用药7d后麻醉大鼠摘取角膜行组织学检查,并于透射电镜下观察角膜超微结构的变化。结果:15只大鼠全部进入结果分析,无脱失。①角膜临床分级:生理盐水组、蓖麻油滴眼组、5g/L,10g/L雷帕霉素滴眼组大鼠角膜临床分级为0级,未见角膜有明显变化;20g/L雷帕霉素滴眼组大鼠在用药第4日角膜临床分级为1级,角膜轻度水肿增厚,继续用药未见损害加重。②角膜组织学结构:20g/L雷帕霉素滴眼组大鼠角膜上皮层未见缺损,基底细胞排列紊乱,细胞极性消失,基质层、内皮层未见明显异常。其他4组大鼠角膜角膜结构完整,上皮层细胞排列整齐,角膜基质层厚度正常,内皮层无断裂。③角膜超微结构:20g/L雷帕霉素滴眼组大鼠角膜上皮细胞间隙扩大,细胞肿胀;内皮细胞线粒体肿胀,内质网扩张,糖原颗粒大量增加。其他4组大鼠角膜上皮及内皮细胞未见异常。结论:以蓖麻油为基质的10g/L及其以下剂量雷帕霉素滴眼剂对大鼠角膜无明显毒性作用;蓖麻油作为滴眼剂基质是安全的。
AIM： Rapamycin is dissolved in castor oil for medicine. To observe the toxicity of rapamycin eye drops in rat comeas, understand the medical safety and suitable dosage and provide basis for cornea transplantation. METHODS： The experiment was conducted from June to October 2006 in the Central Laboratory of Zhujiang Hospital, Southern Medical University. Totally 15 SD rats were selected and randomly divided into 5 groups： saline group, castor oil eye drops group, 5 g/L,10 g/L and 20 g/L rapamycin eye drops group with 3 in each group. After adaptive culture for 1 week, the trail was conducted. The medicine was treated in double eyes of the rats, with different eye drops, 6 times a day, 1 drop once, for 7 days. Rat corneas were checked by slit lamp microscope everyday, and graded in clinic： 0 grade as clearing corneas without dropsy, with clear specular reflection; 1 grade as low cornea clarity, clear specular reflection. 7 days later, histopathological method was carded out on corneas. Ultrastructural change of corneas was observed by transmission electron microscope. RESULTS： Totally 15 rats were involved in the result analysis, no drop-out. （1）Clinical grading of corneas： Corneas were 0 grade and no cornea was changed in saline group, castor oil eye drops group and 5 g/L and 10 g/L rapamycin eye drops group. Corneas were 1 grade 20 g/L rapamycin eye drops group on the 4^th day, and corneas were mild dropsy and thickening but did not become severe. （2）Histological structure of corneas： No defect in corneal epithelium, stroma cells arranged disorderedly, cell polarity disappeared, no obvious abnormity appeared in substantia propria layer and endothelial layer. In other 4 groups, the corneal structure was complete, upper cortical cells arranged well, the depth of corneal stroma was normal, and no breaking in endothelial layer.（3）Comeal ultramicrostructure： Interstitial space of corneal epithelium enlarged, swelled, chondrosome swelled, endoplasmic reticulum expanded and glycogenosome was greatly increased in the 20 g/L rapamycin eye drops group. In other 4 groups, there was no abnormity in corneal endothelial cells and endotheliocytes. CONCLUSION： 5 g/L and 10 g/L rapamycin eye drops do no harm to rat corneas. Castor oil is a good kind of ophthalmic solution solvent.
出处
《中国组织工程研究与临床康复》
CAS
CSCD
北大核心
2007年第21期4101-4104,共4页
Journal of Clinical Rehabilitative Tissue Engineering Research
