米诺环素对急性视神经炎视神经轴突及Caspase-3表达的影响

Effects of minocycline on optic nerve axons and Caspase-3 expression of experimental optic neuritis in rats

目的:探讨米诺环素对急性视神经炎的影响,并与甲基强的松龙比较。方法:雌性Wistar大鼠22只随机分为正常组、EAE组、米诺环素组、甲基强的松龙组(MP组)。观察视神经病理改变,免疫组织化学法检测视网膜神经节细胞(retinal ganglion cells,RGCs)中Caspase-3蛋白表达。结果:EAE组视神经光镜下表现为神经纤维空泡样变性,轴突不规则肿胀,大量炎性细胞浸润。EAE组、米诺环素组、MP组与正常组视神经轴突占横切面积比例相比,差异均有显著统计学意义(P<0.01),米诺环素组、MP组与EAE组间的差异均有统计学意义(P<0.05)。正常大鼠视网膜几乎未见Caspase-3蛋白表达,EAE组、MP组与米诺环素组间的差异均有统计学意义(P<0.05),MP组与EAE组间的差异有统计学意义(P<0.05)。结论:甲基强的松龙可减轻脱髓鞘性视神经炎轴突损伤,但不能减少RGCs中Caspase-3的表达。米诺环素可下调Caspase-3在视网膜中表达,提示米诺环素可通过抑制RGCs中Caspase-3活性,介导对脱髓鞘性视神经炎RGCs的保护作用。

AIM： To investigate the effects of minocycline on optic nerve axons and Caspase-3 expression of experimental optic neuritis in Wistar rats. METHODS： Twenty-two female experimental Wistar rats were assigned to four groups randomly： normal group and experimental autoimmue encephalomyelitis group （EAE group）, minocycline group, methlprednisolone group（MP group）. The pathological changes of optic nerve were observed and the expression of Caspase-3 in retinal ganglion cells （ RGCs ） was detected by immunohistochemistry. RESULTS： In EAE group, the optic nerve fibers showed bulb-like degeneration, the axis irregular swelling, a quantity of inflammatory cell infiltrating under light microscope. The axons showed bulb-like degeneration, myelin sheaths were loose, microtubule and microfilament disappeared under electron microscopy. The area percentage of axons：there was very significant difference（ P〈 0.01 ） ,when EAE group , minocycline group and MP group compared with normal group. There was significant difference（ P 〈 0.05）, when minocycline group and MP group compared with EAE group. In normal rats , there was little expression of Caspase-3 in retina. There was significant difference（ P〈 0.05）, when EAE group and MP group compared with minocycline group. There was significant difference（ P 〈 0. 05）, when MP group compared with EAE group CONCLUSION： Methlprednisolone can reduce demyelinating optic nerve axons injury, but can not reduce the expression of Caspase-3 in RGCs. Minocycline can downregulate the expression of Caspase-3 in retina, which show that minocycline has a marked protection of RGCs in demyelinating optic neuritis by inhibiting the expression of Caspase-3.