TLR4/NF-κB信号转导途径在视神经损伤中的作用及意义  

Effect and significance of TLR4/NF-κB signaling pathway in optic nerve injury

作　　者：杨澎[1] 赵尚峰[1] 康军[1] 张家亮[1] 孙思[1] 傅继弟[1] 

机构地区：[1]首都医科大学附属北京同仁医院神经外科,北京100730

出　　处：《中国卫生检验杂志》2015年第20期3423-3425,共3页Chinese Journal of Health Laboratory Technology

基　　金：973计划项目资助(2005CB724302);北京市科委首都临床特色应用研究项目(Z131107002213085)

摘　　要：目的研究大鼠视神经夹挫伤后视神经和视网膜节细胞形态学变化,以及TLR4/NF-κB信号转导途径在视神经中的表达及作用。方法制作大鼠球后视神经夹挫伤动物模型,分别于伤后1 d、7 d、14 d处死,通过HE染色观察视神经组织以及视网膜RGCs的变化,Western bolt方法监测TLR4和NF-κB在视神经表达的动态变化,并观察Myd88抑制肽抑制该信号转导途径后的相应变化。结果视神经损伤后,RGCs数量随着损伤时间的推移,呈进行性减少,给予Myd88抑制剂治疗后能够明显缓解视神经损伤导致的RGCs数量减少(P<0.05);TRL4表达伤后第1 d即显著增加,并在14 d后达到高点;NF-κB的表达在损伤后7 d没有明显变化,14 d表达明显增加,而给予Myd88抑制剂治疗后,能够明显减少视神经损伤后TLR4和NF-κB的表达。结论视神经损伤后,TLR4/NF-κB信号途径参与了视网膜节细胞的凋亡过程,抑制该信号转导途径能够有效地缓解损伤后视神经功能障碍。Objective To observe the morphological changes in optic nerve and retinal gangliocytes（ RGCs）,as well as the expression and effect of TLR4 / NF-κB signaling pathway in rats with optic nerve contusion. Methods Intraorbital optic nerve contusion models in rats were established,and the animals were executed on the 1st,7thand 14^th day after injury. The morphological changes in optic nerve and RGCs were observed through HE staining; the expression of TLR-4 and NF-κB protein were evaluated through Western Blot; and these changes were compared with those of intravitreal injection of Myd88 inhibiting peptide（ MIP）. Results After the injury of optic nerve injury,the number of RGCs decreased with the injury time. After treatment with Myd88 inhibitor,the number of RGCs in optic nerve injury can be relieved obviously（ P 0. 05）. TRL4 expression was significantly increased after the first Day,and reached the peak after the 14thday; the expression of NF-κBwas not significantly changed after injury,and the expression of the 14 thday was significantly increased; while after treatment with Myd88 inhibitor,expression of TLR 4 and NF-κBcan significantly reduce after optic nerve injury. Conclusion After optic nerve injury,TLR4 / NF-κB signaling pathway participated in the retinal ganglion cell apoptosis,and inhibiting the signal transduction pathway could effectively alleviate the damage of optic nerve dysfunction.

关 键 词：视神经损伤 视神经节细胞 TOLL样受体4 核转录因子kappa B(NF-κB) 髓样分化因子抑制剂 

分 类 号：R774.1[医药卫生—眼科]