冻干血小板用于动物创面治疗的初步安全性评价  

Preliminary safety evaluation of freeze-dried platelets for wound treatment in animals

作　　者：唐艳姣 单桂秋[1,2] 马静[1] 吕品[2] 周谋[2] 林放[2] 张爽[2] 

机构地区：[1]南方医科大学研究生院,广东广州510515 [2]广州军区广州总医院

出　　处：《中国输血杂志》2016年第4期364-367,共4页Chinese Journal of Blood Transfusion

基　　金：国家科技重大专项(2011ZXJ09104-07C)

摘　　要：目的对冻干血小板FDP用于动物创面愈合的治疗做初步安全性评价。方法 FDP单次皮肤刺激试验选择10只SD大鼠,采用自身对照,背部左侧皮肤为实验组:用棉签涂抹0.6 m L复水化FDP;右侧为空白对照组:涂抹0.6 m L生理盐水;于涂抹后1、24、48及72 h观察2组大鼠涂敷区皮肤是否出现红斑、水肿等刺激反应。重复给药毒性试验选择32只新西兰白兔建立皮损模型,随机均分为实验组与空白对照组,前者每天涂抹复水化FDP 0.6 m L/次,后者每天涂抹生理盐水0.6 m L/次,连续涂抹28 d,观察1次/d,测体重1次/周,于涂敷前及涂敷d7、d14、d21、d28分别采集动物血样检测血常规和相关生化指标,并取涂敷区皮肤组织行组织病理学检查。结果单次皮肤刺激试验:2组大鼠皮肤均未出现水肿、红斑等刺激反应。重复给药毒性试验:试验周期中2组动物均未出现体重减轻、一般行为异常及死亡,体重、血常规及生化指标检测结果相近(P>0.05),FDP组动物在实验d7 d14、d21及d28的WBC(×109/L)分别为12.20±1.28 vs 8.63±1.71 vs 6.90±1.21 vs 7.60±1.36(P<0.05);2组动物组内不同时间点的Cr波动明显(P<0.01)。组织病理学检查:2组受试动物涂敷区局部皮肤未见明显组织病理学改变。结论FDP对实验动物没有明显的刺激反应,对动物局部损伤皮肤连续涂敷28 d未见明显毒性反应,其作为外敷生物制剂的初步安全性评价合格。Objective To determine the toxicity profile of freeze-dried platelets（ FDP） following single or multiple skin recovery therapy,and to evaluate the safety of FDP in wound healing. Methods 10 SD rats were used in the single-dose skin stimulation study. The dorsal aspect of the rats was prepared. Skin stimulation was conducted on one side of back in group FDP,and conducted on the other side on group blank control（ group BC）. The appearance of erythema and edema was observed in the skin on 1st,24 th,48th and 72 nd hour after single application of FDP and sterile saline. In the multiple dose toxicity study,32 New Zealand rabbits were divided into two groups： group FDP and group BC. FDP and sterile saline were applied daily to rabbits for 28 days. The general behavior of the rabbits was observed every day. The weight of the rabbits was tested every week. The hematological and blood biochemical parameters and histopathology were assessed before the experiment and on 7th day,14 th day,21 st day and 28 th day. Results From the single-dose skin stimulation study,FDP and sterile saline did not induce erythema and edema. In the multiple dose toxicity study on rabbits,the two groups did not experience a reduction of body weight,abnormal behavior or death. There was no significant difference（ P 0. 05） in rabbits＇ body weight,routine blood work and biochemical detection between the two groups. On day 7,the WBC of rabbits from group FDP was higher than that on day 14,21 and 28（ P 0. 05）. The Cr was fluctuated in two group. Histologically,there was no histopathological change on the skin of all experiment animals. Conclusion FDP did not induce obvious skin stimulation in SD rats and New Zealand rabbits. It exhibited no significant toxicity to rabbits after 28 days of use. These results indicate that FDP is qualified in preliminary safety evaluation as a kind of novel biological agent.

关 键 词：冻干血小板 创面治疗 安全性评价 动物实验 皮肤刺激 毒性试验 

分 类 号：R457[医药卫生—治疗学] R331.143[医药卫生—临床医学]