长春胺对非动脉炎性前部缺血性视神经病变大鼠模型视神经保护作用及其机制  

Protective effect and mechanism of Vincamine on the optic nerve of a rat model of non-arteritic anterior ischemic optic neuropathy

作　　者：付梅 李璐[1] 梁超群[1] 苏钰[1] 刘珏君 陈长征[1] FU Mei;LI Lu;LIANG Chaoqun;SU Yu;LIU Juejun;CHEN Changzheng(Eye Center,Renmin Hospital of Wuhan University,Wuhan 430060,Hubei,China)

机构地区：[1]武汉大学人民医院眼科中心,湖北武汉430060

出　　处：《武汉大学学报（医学版）》2022年第1期34-39,共6页Medical Journal of Wuhan University

基　　金：国家自然科学基金青年基金资助项目(编号:81600740);武汉大学自主科研基金资助项目(编号:2042019kf0071)。

摘　　要：目的:研究长春胺对非动脉炎性前部缺血性视神经病变(NAION)大鼠模型的潜在神经保护作用。方法:90只SD大鼠随机分为正常组、单纯模型组、造模羧甲基纤维素钠灌胃组(NaCMC)组、长春胺组、造模PI3K抑制剂LY294002玻璃体腔注射(IVT LY)+长春胺组、造模DMSO玻璃体腔注射(IVT DMSO)+长春胺组。对各组进行眼底照相,眼底荧光血管造影,血清一氧化氮(NO)浓度检测,HE染色观察视网膜形态,甲苯胺蓝染色观察视神经轴突形态,免疫荧光染色计数视网膜神经节细胞(RGCs),实时定量PCR检测p-AKT、eNOS含量。结果:rNAION大鼠(rNAION)造模成功后第1天即可见大鼠视盘水肿,边界模糊。造模后第28天,长春胺组的NO浓度显著高于正常对照组、单纯模型组及NaCMC组。与单纯模型组相比,长春胺组RGCs数量明显增加(P<0.05),p-AKT、eNOS含量明显增加(P<0.05)。IVT LY+长春胺组RGCs数量及p-AKT、eNOS含量较长春胺组明显减少(P<0.05)。结论:长春胺可能通过PI3K/AKT/eNOS信号通路发挥视神经保护作用,有望成为NAION的有效治疗药物。Objective:To study the potential neuroprotective effect of Vincamine in a rat model of non-arteritic anterior ischemic optic neuropathy(NAION).Methods:Ninety SD rats were randomly divided into six groups,including normal control group,simple model group,carboxymethylcellulose sodium(NaCMC)group,Vincamine group,intravitreal injection of PI3K inhibitor LY294002(IVT LY)+Vincamine group,and intravitreal injection of DMSO(IVT DMSO)+Vincamine group.Fundus photography,fundus fluorescein angiography,measurement of serum nitric oxide(NO)concentration,hematoxylin and eosin(HE)staining to observe the morphology of the retina,toluidine blue staining to observe the morphology of optic nerve axons,flat-mount immunofluorescence to count retinal ganglion cells(RGCs),and real-time quantitative PCR to detect the expression of p-AKT and eNOS were performed in all the six groups.Results:Optic disc edema and blurred optic disc borders were seen in the rat model of NAION(rNAION)on the first day after photodynamic induction.28 days after induction,the Vincamine group had a higher NO concentration than the normal control group,simple model group,and NaCMC group,respectively.Compared with that respectively in simple model group,the number of RGCs in Vincamine group increased significantly(P<0.05),and the expression of p-AKT and eNOS increased significantly(P<0.05).The number of RGCs and the expression of p-AKT and eNOS in IVT LY+Vincamine group were significantly reduced as com-pared with those in Vincamine group(P<0.05).Conclusion:Vincamine may exert optic neuroprotection through the PI3K/AKT/eNOS signaling pathway and may become an effective drug for NAION.

关 键 词：非动脉炎性前部缺血性视神经病变 长春胺 视网膜神经节细胞 神经保护 

分 类 号：R774.6[医药卫生—眼科]