COX-2抑制剂对NMDA损伤视网膜神经节细胞层神经元的保护机制研究  

Neuroprotective mechanism of cyclooxygenase-2 inhibitor on rat retinal ganglion cell layer neurons damage induced by N-methyl-D-aspartate

作　　者：徐露[1] 田晗[1] 李玉桑[1] 姚光强[1] 唐和斌[1] 奉黎静[1] 刘敏[1] 

机构地区：[1]中南民族大学药学院,湖北省武汉市430074

出　　处：《眼科新进展》2014年第4期301-305,共5页Recent Advances in Ophthalmology

基　　金：国家自然科学基金资助(编号:81202942);中南民族大学科研基金资助(编号:XTZ10001;GCX12073)~~

摘　　要：目的探讨COX-2抑制剂NS398对N-甲基-D天冬氨酸(N-methyl-D-aspartate,NMDA)诱导的大鼠视网膜损伤模型的神经保护作用。方法 25只大鼠随机分成5组:正常组、NMDA组、NMDA+不同剂量NS-398(1 ng·mL-1、10 ng·mL-1、100ng·mL-1)组。NMDA组于大鼠双眼玻璃体内注射5μL NMDA(40 nmol·L-1),NMDA+不同剂量NS-398组于大鼠双眼玻璃体内注射5μL NMDA(40 nmol·L-1)及NS-398(1 ng·mL-1,10 ng·mL-1,100 ng·mL-1)。7 d后,取眼球组织,并对视网膜神经节细胞层(retinal ganglion cell layer,RGCL)神经元数目进行计数,采用TUNEL法和免疫组织化学染色分别测定RGCL神经元的凋亡以及视网膜组织中caspase-3、COX-2的表达。结果 NMDA组大鼠RGCL神经元数目为正常大鼠的(47±3)%,与NMDA组比较,NMDA+NS-398组的RGCL神经元数目明显增多,低、中、高三种剂量组RGCL神经元数目依次为正常组的(63±5)%、(82±7)%、(73±3)%;NMDA组caspase-3的表达为正常组的(327±21)%,NMDA+NS-398组caspase-3的表达显著下调,低、中、高三种剂量组caspase-3的表达依次为正常组的(223±14)%、(197±18)%、(261±16)%;NMDA组COX-2的表达为正常组的(315±11)%,NMDA+NS-398组的表达显著下调,低、中、高三种剂量组COX-2的表达依次为正常组的(280±20)%、(233±16)%、(255±19)%。结论抑制COX-2表达能够抑制NMDA导致的RGCL细胞凋亡,对视网膜产生保护作用。Objective To investigate the protection mechanisms of COX-2 inhibi- tor （ NS398 ） on the rat retinal damage induced by n-methyl-D-aspartate （NMDA）. Methods Twenty-five Sprague-Dawley rats were divided into five groups： control group, NMDA group and NMDA ＋ NS-398 with different concentrations （ 1 ng. mL-1, 10 ng . mL-1 , 100 ng.mL-1 ）group. Rats in the NMDA group were given 5 μL NMDA （40 nmol . L-1 ）. Rats in NMDA ＋ NS-398 with different concentration groups were giv- en with an intravitreal injection （5 μL）of NMDA （40 nmol . L-1 ）and NS-398 （1 ng.mL-1 , 10 ng .mL-1, 100 ng. mL-1 ）. Seven days after NMDA treatment, the eye tis- sues were taken from those rats. The neuron numbers of retinal ganglion cell layer （RGCL） were counted, the apoptosis of RGCL cell was determined by TUNEL assay, and the expressions of caspase-3 and COX-2 in the rats＇ retinas were measured by im- munohistochemical staining. Results Neuron numbers in RGCL of NMDA group ＋ low-, middle-, high- concentration NS-398 groups were greater （63% ± 5% , 82% ± 7% , 73% ± 3% of control, respectively） than that in NMDA group （47%± 3% of control）. The protein expressions of caspase-3 in the NMDA ＋ low-, middle-, high-concentration NS- 398 groups were significantly lower （223%± 14% , 197% ±18% , 261%± 16% of control, respectively）as compared with those in NMDA group （327% _＋21% of control）. Also the expressions of COX-2 in the NMDA ＋ low-, middle-, high-concentration NS-398 groups were significantly lower （280%±20%, 233%± 16% , 255%± 19% of control, respective-ly）as compared with NMDA group （315%± 11% of control）. Conclusion Inhibition of COX-2 can inhibit the NMDA-in- duced apoptosis of RGCL cells in the rats＇ retina, which may have a protective effect on the retina.

关 键 词：视网膜 N-甲基-D天冬氨酸 COX-2抑制剂 细胞凋亡 神经保护 

分 类 号：R775[医药卫生—眼科]