胸腺素β4壳聚糖纳米粒的制备及其对NF-κB表达调节治疗兔角膜创伤  

Preparation of thymosin β4 chitosan nanoparticles and its efficiency in treatment of corneal trauma by regulating NF-κB

作　　者：计岩[1] 赵敏[1] 邬桂玉[1] 

机构地区：[1]重庆医科大学附属第一医院眼科,重庆市眼科学重点实验室,重庆400016

出　　处：《第三军医大学学报》2013年第14期1466-1470,共5页Journal of Third Military Medical University

基　　金：重庆市科委科学基金(CSTC2008AC0086);重庆医科大学附属第一医院课题(YXJJ 2009-09)~~

摘　　要：目的考察胸腺素β4壳聚糖(thymosinβ4 chitosan,Tβ4/CS)纳米粒的体外性质及其在兔角膜创伤中通过调节核转录因子NF-κB的表达修复角膜的作用。方法采用离子交联法制备Tβ4/CS纳米粒,考察纳米粒粒径、zeta电位、包封率及体外释放情况。2.0 mg/L的Tβ4/CS纳米粒混悬液滴兔眼,右眼为实验眼,左眼为对照眼,HE染色观察眼表组织学变化,并观察其是否有眼表毒性。建立兔角膜创伤模型,右眼作为实验眼,采用单纯随机抽样法,分为Tβ4/CS纳米粒组(A组)、Tβ4滴眼液组(B组)、损伤对照组(C组),每组20只。治疗后1、3、7、14 d大体观察及HE染色观察角膜修复情况,并使用RT-PCR方法检测角膜核转录因子NF-κB的表达。结果 Tβ4/CS纳米粒大部分呈规则的球型,粒径为(354.0±1.6)nm,zeta电位为(22.5±0.7)mV,包封率为(76.2±2.8)%,体系较为稳定,具有缓释功能。Tβ4/CS纳米粒滴眼液对兔眼睑、结膜、角膜无损害;明显下调兔创伤角膜中的NF-κB的表达促进角膜修复,各时间点各组间差异具有统计学意义(P<0.01)。结论胸腺素β4壳聚糖纳米粒滴眼液通过下调兔创伤角膜中的NF-κB的表达促进角膜修复,对兔眼表无损害。Objective To investigate the in vitro properties of nanoparticles containing thymosin β4 chitosan （Tβ4/CS）, and determine its effect on the repair of rabbit corneal wound by regulating the expression of nuclear transcription factor NF-κB. Methods The ionotropic gelation was employed to produce Tβ4/CS nanoparticles. Then particle size, zeta potential, encapsulation efficiency and release in vitro were studied. Tβ4/CS nanoparticle suspension drops, 2.0 mg/L, was used to drop on the eyes of the rabbit for the toxicity of the particles, while the right eyes were set as normal control. HE staining was used to stain the ocular surface tissue, to observe whether there exists ocular surface toxicity or not. In rabbit corneal trauma model, all rab- bits＇ right eyes were set as the experimental subject, and the rabbits were divided into TI^4/CS nanoparticle group （A） , Tβ4 group （B） and control group （C） , with 20 animals in each group, General observation and HE staining were carried in the corneal wound on 1, 3, 7, and 14 d after treatment, and RT-PCR was used to detect the expression of corneal nuclear transcription factor NF-κB. Results Tβ4/CS nanoparticles were most- ly in round shape, in a diameter of 354.0 ± 1.6 nm, with a zeta potential of 22.5 ± 0.7 mV, and encapsulation efficiency of （76.2 ± 2.8） %. The produced Tβ4/CS nanopartieles were stable, with a sustained-released func- tion. The toxicity test indicated that Tβ4/CS nanoparticles eye drops, 2.0 mg/L, were not harmful for the rab- bit eyelids, conjunctiva, and comea. The Tβ4/CS nanoparticles down-regulated the expression of NF-κB in rabbit traumatic comeal to promote corneal repair significantly, at each time point than the other 2 groups （ P 〈 0. 01 ）. Conclusion The thymosin β4 chitosan nanoparticles eye drops can be used to promote corneal repair in the rabbit traumatic corneal by down-regulating NF-κB, without any harm to the ocular surface.

关 键 词：角膜创伤愈合 胸腺素Β4 纳米粒 药物缓释 核转录因子 

分 类 号：R772.2[医药卫生—眼科] R966[医药卫生—临床医学]