方法：60只新生SD大鼠随机分为6组：正常对照组(Nor)、正常+PBS治疗组(Nor+PBS)、正常+NEP1-40治疗组(Nor+NEP)、模型对照组(MD)、模型+PBS治疗组(MD+PBS)及模型+NEP1-40治疗组(MD+NEP)。模型组大鼠于出生后21d缝合右侧眼睑建立单眼剥夺弱视模型，于45日龄时打开剥夺眼，对各组大鼠行闪光视觉诱发电位(F-VEP)检测，确定单眼剥夺模型建立成功后，对需给药的各组大鼠按组别给予NEP1-40或PBS侧脑室注药治疗7d。于52日龄时对各组大鼠再次行F-VEP检测后处死动物，取左侧视皮层进行透射电镜观察突触超微结构变化。

结果：45日龄时F-VEP检测示，MD组、MD+PBS组及MD+NEP组与Nor组比较，P波潜伏期延长，波幅降低(P<0.05)； 52日龄时F-VEP检测示，MD+NEP组与MD组、MD+PBS组大鼠比较，右眼F-VEP的P波潜伏期及波幅差异有统计学意义(P<0.05)，而与Nor组比较差异无统计学意义(P>0.05)； MD+PBS组与MD组大鼠比较，右眼F-VEP的P波潜伏期及波幅差异无统计学意义(P>0.05)，而与Nor组比较差异有统计学意义(P<0.05)。透射电镜观察视皮层神经元突触界面结构参数：与Nor组比较，MD组大鼠剥夺眼对侧视皮层神经元突触间隙增大，突触活性区长度缩短，突触界面曲率减小，突触后致密物厚度变薄(P<0.05)。MD+NEP组大鼠剥夺眼对侧视皮层神经元突触界面结构参数的各项指标均较MD组、MD+PBS组明显改善(P<0.05)，与Nor组相比除突触间隙外(P<0.05)，其余各项参数差异无统计学意义(P>0.05)。MD+PBS组与MD组大鼠比较剥夺眼对侧视皮层神经元突触界面结构参数的各项指标差异均无统计学意义(P>0.05)，而与Nor组比较差异有统计学意义(P<0.05)。

结论：NEP1-40可使成年单眼剥夺弱视大鼠剥夺眼对侧视皮层神经元的突触界面结构参数得以恢复，F-VEP的P波潜伏期及波幅恢复至正常水平，重新“激活”被抑制的视皮层结构及功能可塑性，为成年弱视患者提供新的治疗途径奠定了理论基础。

METHODS: Totally 60 neonatal rats were randomly allocated into 6 groups: normal animals(Nor), normal animals treated with PBS(Nor+PBS)or NEP1-40(Nor+NEP), MD animals without any treatment(MD), MD animals treated with PBS(MD + PBS)or NEP1-40(MD + NEP). We subjected P21 rats to monocular deprivation model until P45. Then the deprived eyes of MD model rats were reopened and followed by NEP1-40 or PBS administration for 7 days. Ultrastructral modifications of synaptic junctions and objective visual function were examined at P52 to determine the therapeutic effects of NEP1-40.

RESULTS: The objective visual function examined by F-VEP: At P45, F-VEP showed that compared with rats in Nor group, deprived eyes of rats in MD group, MD+PBS group and MD+NEP group displayed a longer latency(P<0.05)and a smaller amplitude(P<0.05); At P52, we could see that comparing with the MD group and MD + PBS group, the latencies of F-VEP in MD+NEP group were shortened and the amplitudes were increased(P<0.05), which were similar with that of in Nor group(Nor vs MD+NEP, P>0.05). The structural modifications of synaptic junctions examined by electromicrographs: All of the structural parameters of the synaptic junction in visual cortex were altered by monocular deprivation in MD group compared with the Nor group, displaying an increased width of synaptic clefts, shortened synaptic active zone, decreased curvature of synaptic interface and decreased thickness of PSD. However, synaptic ultrastructural analysis showed that NEP1-40 treatment could recover the entire structural index in monocular deprivation rats(MD vs MD+PBS vs MD+NEP, P<0.05)but not normal rats(Nor vs Nor+PBS vs Nor+NEP, P>0.05). It was noteworthy that, although the width of synaptic clefts in MD+NEP group decreased remarkably in comparison with that of in MD group, it still had not reach the normal level(Nor vs MD+NEP, P>0.05).

CONCLUSION: NEP1-40 could recover the structural modifications of synaptic junctions of neurons in visual cortex contralateral to deprived eye, as well as the objective visual function of deprived eye, which indicated a new role for NEP1-40 in reactivation of visual cortical plasticity from monocular deprivation in adult rats and offered the theoretical foundation for curing adult patients with amblyopia in the clinic.