Nogo受体在早期糖尿病大鼠视网膜神经节细胞凋亡中的作用

Role of NgR on the apoptosis of retinal ganglion cell in the early stage of diabetic rats

目的:探讨Nogo受体(nogo receptor,NgR)在糖尿病(diabetes mellitus,DM)大鼠视网膜神经节细胞凋亡中的作用及机制。方法:链脲佐菌素诱导SD大鼠DM模型,实验分4组,对照组;DM组;siNgR组:DM大鼠玻璃体内给予NgR反义核苷酸序列;siRNA空白组:DM大鼠玻璃体内给予阴性核苷酸序列。1mo后TUNEL染色检测视网膜神经节细胞(retinal ganglion cell,RGC)凋亡,试剂盒检测视网膜丙二醛(malondialdehyde,MDA)含量,Western-blot检测视网膜NgR及caspase-3含量。结果:对照组、DM组、siRNA空白组及siNgR组MDA含量分别为3.74±0.49,7.21±0.96,6.41±1.34及4.02±0.53nmol/mg prot。与对照组相比,DM组及siRNA空白组视网膜RGC凋亡增加,NgR及caspase-3表达上调,MDA含量升高(P<0.05),而siNgR组视网膜RGC数量、NgR及caspase-3表达、MDA含量较对照组均无明显变化(P>0.05)。结论:NgR表达增加是糖尿病RGC凋亡的重要原因之一,其机制可能与NgR诱导视网膜氧化应激、上调caspase-3表达有关。

AIM ： To explore the role and underlying mechanisms of nogo receptor（NgR） on the apoptosis of retinal ganglion cell in rats with diabetes mellitus（DM）. METHODS： SD rats were used for inducing DM models by administrating streptozotocin. Studies were performed with control group, DM group, siNgR group： DM rats intravitreal administration of anti- NgR nucleotide, and siRNA control group： DM rats intravitreally administrated with negative nucleotide. One month later, TUNEL staining was conducted to detect apoptosis of retinal ganglion cell （RGC）, level of retinal malondialdehyde （MDA） were detected with kit, and expression of NgR and caspase-3 were observed with Western blot. RESULTS： The level of retinal MDA in control group, DM group, siNgR group and siRNA control group were 3.74±0.49, 7.21±0.96, 6.41 ±1.34 and 4.02±0.53nmol/mg prot respectively. A significant increase in the number of TUNEL-positive RGC, the expression of retinal NgR andcaspase-3, and the level of retinal MDA were detected in DM and siNgR groups compared with control group （ P〈 0. 05）. However, the number of TUNEL-positive RGC, the expression of retinal NgR and caspase-3, and the level of retinal MDA showed no difference between control group and siNgR group （P〉0.05）. CONCLUSION： NgR induces retinal oxidative stress and up-regulation of retinal caspase-3, playing an important role in the apoptosis of diabetic RGC.