摘要
目的探究氟西汀对单眼剥夺弱视大鼠视皮质神经细胞突触可塑性的影响与机制。方法60只SPF级雄性SD大鼠取10只为对照组,余50只构建单眼剥夺弱视大鼠模型。建模成功的50只大鼠依据随机数字表法分为阳性药组,模型组,低、中、高剂量组,每组10只。低、中、高剂量组分别腹腔注射5、10、20 mg/(kg·d)氟西汀;阳性药组灌胃左旋多巴80 mg/(kg·d);模型组、对照组腹腔注射等量生理盐水,各组给药28 d。检测各组大鼠P_(100)潜伏期、P_(100)幅值;观察各组大鼠视皮层神经元细胞突触超微结构变化;检测各组大鼠视皮层组织中ERK1/2、p-ERK1/2、CREB、p-CREB蛋白水平。结果模型组大鼠P_(100)潜伏期、突触间隙与突触致密厚度高于对照组,P_(100)幅值和视皮层组织p-ERK1/2/ERK1/2、p-CREB/CREB低于对照组,差异有统计学意义(P<0.05)。低、中、高剂量组大鼠P_(100)潜伏期、突触间隙与突触致密厚度低于模型组,P_(100)幅值和视皮层组织p-ERK1/2/ERK1/2、p-CREB/CREB高于模型组;中、高剂量组大鼠P_(100)潜伏期、突触间隙与突触致密厚度低于低剂量组,P_(100)幅值和视皮层组织p-ERK1/2/ERK1/2、p-CREB/CREB高于低剂量组;高剂量组大鼠P_(100)潜伏期、突触间隙与突触致密厚度低于中剂量组,P_(100)幅值和视皮层组织p-ERK1/2/ERK1/2、p-CREB/CREB高于中剂量组,差异有统计学意义(P<0.05)。与模型组比较,低、中、高剂量组大鼠视皮层神经元突触和髓鞘板层结构稍清晰。结论氟西汀能重塑单眼剥夺弱视大鼠视皮质神经细胞突触超微结构,激活视皮层结构可塑性,改善大鼠视觉功能,可能是通过激活ERK/CREB通路实现。
Objective To investigate the effect of Fluoxetine on synaptic plasticity of optic cortical neuron cells in monocular deprived amblyopia rats and its related mechanism.Methods Ten of 60 SPF male SD rats were selected as the control group,and the other 50 rats were used to construct the monocular deprived amblyopia rat model.The 50 rats with successful modeling were divided into positive drug group,model group,low,medium,and high dose groups by random number table method,with 10 rats in each group.The low,medium,and high dose groups were intraperitoneally injected with 5,10,and 20 mg/(kg·d)Fluoxetine;the positive drug group was intraperitoneally injected with 80 mg/(kg·d)Levodopa;and the model group and the control group were intraperitoneally injected with the same amount of normal saline.Each group was treated for 28 days.P_(100) latency and P_(100) amplitude in each group were measured;the ultrastructural changes of synapses of neurons in visual cortex in each group were observed;the ERK1/2,p-ERK1/2,CREB,and p-CREB protein in visual cortex in each group were detected.Results The P_(100) latency,synaptic gap,and synaptic density thickness in the model group were higher than those in the control group,and the P_(100) amplitude and p-ERK1/2/ERK1/2,and p-CREB/CREB in visual cortex were lower than those in the control group(P<0.05).The P_(100) latency,synaptic gap,and synaptic density thickness in the low,medium,and high dose groups were lower than those in the model group,and the P_(100) amplitude,p-ERK1/2/ERK1/2,and p-CREB/CREB in the visual cortex were higher than those in the model group;the P_(100) latency,synaptic space,and synaptic density thickness in the middle and high dose groups were lower than those in the low dose group,and the P_(100) amplitude,p-ERK1/2/ERK1/2,and p-CREB/CREB in the visual cortex were higher than those in the low dose group;the P_(100) latency,synaptic gap,and synaptic density thickness in the high-dose group were lower than those in the medium dose group,and the P_(100) amplitude,p-ERK1/2/ERK1/2,and p-CREB/CREB in the visual cortex were higher than those in the medium dose group(P<0.05).Compared with the model group,the synaptic structure of the visual cortex neurons in the low,medium,and high dose groups was slightly clear,and the myelin sheath lamellar structure was clear.Conclusion Fluoxetine can remodel the synaptic ultrastructure of visual cortex neurons in monocular deprived amblyopic rats,activate the structural plasticity of visual cortex,and improve the visual function of rats,which may be achieved by activating ERK/CREB pathway.
作者
罗贤令
吴罗玲
LUO Xianling;WU Luoling(Department of Ophthalmology,the First People’s Hospital of Fuyang District,Zhejiang Province,Hangzhou311400,China)
出处
《中国医药导报》
CAS
2022年第30期17-20,共4页
China Medical Herald
基金
浙江省医药卫生科技面上项目(2021419847)。
关键词
单眼剥夺弱视
氟西汀
视皮质神经细胞
突触可塑性
Monocular deprivation amblyopia
Fluoxetine
Optic cortical nerve cells
Synaptic plasticity
