白血病抑制因子对视网膜光感受器细胞光损伤的保护作用及其机制

Protective effect of leukemia inhibitory factor on light induced retinal photoreceptors damage and its mechanisms

目的 探讨白血病抑制因子（LIF）对视网膜光感受器细胞光损伤的保护作用及其机制.方法 选取50只5～6周龄BALB/c小鼠按照随机数字表法随机分为正常对照组10只、光损伤＋LIF组20只和光损伤＋PBS组20只.于光照前4d,光损伤＋LIF组小鼠右眼行玻璃体腔LIF注药,光损伤＋PBS组小鼠右眼行玻璃体腔PBS注药.采用4 000 lx白色冷光源对光损伤＋LIF组和光损伤＋PBS组小鼠持续照射4h建立小鼠视网膜光损伤模型.分别采用闪光视网膜电图（fERG）和组织病理学检查检测视网膜光感受器细胞的功能和形态学变化.应用实时荧光定量PCR法检测小鼠视网膜中Jak3、STAT3及凋亡相关因子Bcl-2、Bax mRNA的相对表达水平. 结果 暗适应ERG检查结果显示,0.01、1、100、200、400 cd·s/m2光强度下光损伤＋PBS组a波振幅较正常对照组和光损伤＋LIF组低,差异均有统计学意义（均P＜0.05）;明适应ERG检查结果显示,在白光、绿光和蓝光刺激下,光损伤＋PBS组b波振幅较正常对照组和光损伤＋LIF组低,差异均有统计学意义（均P＜0.05）.光损伤＋PBS组外核层光感受器细胞数量显著低于正常对照组和光损伤＋LIF组,差异均有统计学意义（均P＜0.05）.与光损伤＋PBS组相比,光损伤＋LIF组Jak3、STAT3、Bcl-2 mRNA的相对表达量显著增加,Bax mRNA的相对表达量显著下降,差异均有统计学意义（均P＜0.05）.结论 LIF对视网膜光感受器细胞光损伤具有保护作用,其可能通过激活Jak3/STAT3信号通道抑制下游Bax/Bcl-2凋亡通道而发挥作用.

Objective To investigate the role of leukemia inhibitory factor （LIF） on retinal photoreceptor cells and the underlying mechanism after light damage.Methods Fifty 5-6 weeks old BALB/c mice were randomly divided into normal control group （10 mice）,light damage＋LIF group （20 mice） and light damage＋PBS group （20 mice）.Four days before exposing to light,the right eye of each animal in light damage＋LIF group and light damage＋PBS group was injected with LIF and PBS,respectively;then the mice in the light damage＋LIF group and light damage＋PBS group were exposed to 4 000 lx intensity of cool white fluorescent light for 4 hours to establish the experimental model of retinal light damage.The function and morphology of retinal photoreceptor cells were detected by flash electroretinogram （fERG） and histopathological examination.Real-time PCR was used to detect the mRNA expression of Jak3,STAT3,and apoptosis-related factor Bcl-2 and Bax.The use of animals is guided by the State Science and Technology Commission＇s regulations on the management of experimental animals.Results The amplitudes of scotopic ERG a wave of 0.01,1,100,200,400 cd · s/m2 light in the light damage ＋ PBS group were significantly lower than those in the normal control group and light damage ＋ LIF group （all at P ＜ 0.05）.The amplitudes of photopic ERG b wave of different color light in the light damage＋PBS group were significantly lower than those in the normal control group and light damage＋LIF group （all at P＜0.05）.The number of photoreceptor nuclei in the light damage＋PBS group was significantly lower than that in the normal control group and light damage＋ LIF group （both at P＜0.05）.Compared with light damage＋PBS group,the relative expression of Jak3,STAT3,Bcl-2 mRNA in light damage＋LIF group were significantly increased （all at P＜0.05）,and the relative expression of Bax mRNA were significantly decreased （P＜0.05）.Conclusions LIF can protect retinal photoreceptor cells from light damage,which may result from the activation of Jak3/STAT3 signaling pathway and inhibition of its downstream Bax/Bcl-2 apoptotic pathway.