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

发布时间：2018-08-02 18:34

【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。
[Abstract]:Objective to investigate the neuroprotective effect of COX-2 inhibitor NS398 on retinal injury induced by N-methyl-D-aspartate in rats. Methods Twenty-five rats were randomly divided into five groups: normal group (n = 10), NS-398 (1 ng ml -1) 10 ng mL-1100ng mL-1. NMDA group was given 5 渭 L NMDA (40 nmol L -1 intravitreous injection of 5 渭 L NMDA (40 nmol L -1 and NS-398 (1 ng ml -1 10 ng mL-1100 ng mL-1) .7 days after intravitreous injection of 5 渭 L NMDA (40 nmol L -1 and 1 ng ml -1 10 ng mL-1100 ng mL-1. The number of (retinal ganglion cell layerus neurons in retinal ganglion cell layer was counted. The apoptosis of RGCL neurons and the expression of caspase-3 COX-2 in retinal tissue were determined by TUNEL and immunohistochemical staining, respectively. Results the number of RGCL neurons in NMDA group was (47 卤3) that of normal rats. Compared with NMDA group, the number of RGCL neurons in NMDA NS-398 group was significantly increased, low and moderate. The number of RGCL neurons was (63 卤5), (82 卤7), (73 卤3) in the normal group, (327 卤21) and (327 卤21) in the normal group respectively. The expression of caspase-3 in the three dose groups was (223 卤14), (197 卤18) and (261 卤16) respectively. The expression of COX-2 was significantly decreased in the normal group (315 卤11). The expression of COX-2 in the middle and middle dose groups was (280 卤20), (233 卤16), (255 卤19) respectively. Conclusion inhibiting the expression of COX-2 can inhibit the apoptosis of RGCL cells induced by NMDA and protect the retina.
【作者单位】：中南民族大学药学院;
【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)~~
【分类号】：R774.1

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