摘要背景 氟西汀(Flx)为一种选择性血清素重吸收抑制剂,腹腔内注射可诱发成年大鼠海马区神经的再生和突触的发生,推测其对视皮层视觉可塑性产生促进作用,但口服Flx与成年大鼠视皮层可塑性的关系、其与双眼形觉剥夺(BFD)逆转成年大鼠视皮层可塑性作用的关系等研究鲜见报道. 目的 采用图形视觉诱发电位(PVEP)的方法研究Flx给药时间与成年大鼠视皮层可塑性逆转的关系,比较Flx与BFD逆转成年大鼠视皮层可塑性的效果.方法 采用完全随机分组区组设计多水平实验设计方法将70日龄(P70)的成年Wistar大鼠56只随机分为对照组、Flx2组、Flx4组、Flx6组、Flx8组、BFD组和Flx+BFD组,Flx各组大鼠均给予0.2 mg/ml Flx溶液喂养大鼠分别至PVEP检查前2、4、6、8周,然后改为正常水饮用,于PVEP检查前1周行左跟上下睑缘缝合制备单眼形觉剥夺(MFD)模型;BFD组大鼠在PVEP检查前3周行双眼缝合2周,同时给予正常饮水3周;Flx+ BFD组先用0.2 mg/ml Flx溶液喂养4周,在Flx溶液喂养1周后双眼缝合2周,再于PVEP记录前1周剪开右眼睑行MFD.各组大鼠均行双跟PVEP记录,测量N75-P100振幅,计算FD跟(左眼)/非FD眼(右眼)(C/I)值,并通过比较FD前后大鼠PVEP振幅值的变化评估眼优势的转移. 结果 FD 1周后,Flx4组、Flx6组、Flx8组、BFD组、Flx+BFD组大鼠PVEP C/I值较FD前均明显下降,差异均有统计学意义(t=2.733,P＜0.05;t=2.981,P＜0.05;t=3.619,P＜0.01;t=2.681,P＜0.05;t=4.550,P＜0.01) oFlx4组、Flx6组和Flx8组大鼠FD后左眼PVEP振幅值较FD前明显降低[(17.71±2.24)μV比(31.09±4.13) lμV;(18.93±2.85) μV比(29.59±4.07) μV;(17.94± 1.92) μV比(28.48±3.09) μV],差异均有统计学意义(t=3.348、3.278、4.447,均P＜0.01),而FD前后右眼PVEP振幅的改变差异均无统计学意义(均P＞0.05).FD后BFD组和Flx4+BFD组大鼠左眼PVEP振幅值明显低于FD前,差异均有统计学意义(t=2.497,P＜0.05;t=3.051,P＜0.01),BFD组和Flx+ BFD组大鼠FD后右眼PVEP振幅值明显高于FD前,差异均有统计学意义(t=-4.009,P＜0.01;t=-4.352,P＜0.01). 结论 采用0.2 mg/ml Flx水溶液喂养成年大鼠4周以上及BFD2周的方法均可有效激活成年大鼠视皮层可塑性,延长Flx喂养时间并不能显著提高视觉可塑性重塑的程度.Flx对视觉可塑性重塑的主要作用机制是抑制FD眼反应,而BFD的作用机制是抑制FD眼反应的同时促进非FD眼反应来实现的.Flx喂养与BFD法在逆转成年大鼠视皮层可塑性方面具有协同作用.

abstractsBackground Fluoxetine (Flx),a selective serotonin reuptake inhibitor,promotes neurogenesis and synaptogenesis in the adult hippocampus.So it is inferred that Flx plays a role in promoting visual plasticity of visual cortex.However,the associations of oral administration of Flx with remodeling of visual plasticity and its difference from binocular form deprivation (BFD) are unelucidated.Objective This study was to investigate the influence of Flx application time to visual plasticity and contrast the mechanism between Flx and BFD in the remodeling of visual cortex plasticity in adult rats by pattern visual evoked potential (PVEP).Methods Fifty-six 70-day-old clean Wistar rats were randomized into control group,Flx2 group,Flx4 group,Flx6 group,Flx8 group,BFD group and Flx+BFD group.Flx was orally used at the dosage of 0.2 mg/ml once per day until 2,4,6 and 8 weeks before record of PVEP in the Flx2 group,Flx4 group,Flx6 group,Flx8 group respectively.The eyelids were binocularly sutured for 2 weeks and opened the right eyes 1 week before the record of PVEP to form the BFD and took the normal water in the rats of the BFD group,and the combination of Flx administration and BFD was performed in the Flx+BFD group.All the left eyes of the rats were sutured for 1 week to form the monocular form deprivation (MFD).No any intervene was conducted in the control group.PVEP was binocularly recorded in the rats to measure the amplitude from N75 wave to P100 wave,and amplitude ratio of left eyes and right eyes (C/I) was calculated.The results between before and after FD were compared to assess the shift of ocular dominance.The use and care of the animals followed ARVO Statement.Results The C/I of PVEP was significantly decreased 1 week after FD in comparison with before FD in the Flx4 group,Flx6 group,Flx8 group,BFD group and Flx+BFD group (t=2.733,P＜0.05;t=2.981,P＜0.05;t =3.619,P ＜ 0.01;t =2.681,P ＜ 0.05;t =4.550,P ＜ 0.01).The amplitudes of PVEP were significantly lower in the left eyes after FD than those before FD in the Flx4 group ([17.71±2.24] μV vs.[31.09±4.13] μV),the Flx6 group ([18.93 ±2.85] μV vs.[29.59±4.07] μV) and the Flx8 group ([17.94± 1.92] μV vs.[28.48±3.09] μV)(t =3.348,3.278,4.447,all at P＜0.01),while there were significant differences in the amplitudes of PVEP in the right eyes between before and after FD (all at P＞0.05).The amplitudes of PVEP were reduced in the left eyes after FD in comparison with before FD in the BFD group and Flx4+BFD group (t=2.497,P＜0.05;t=3.051,P＜0.01),however,they were raised in the right eyes in both BFD group and Flx+BFD group (t=-4.009,P＜0.01;t=-4.352,P＜0.01).Conclusions Both 0.2 mg/ml Flx drinking for over 4 weeks and BFD for 2 weeks can restore visual cortex plasticity in the adult rats.Increasing the dosage time of Flx appears to be incapable to increase the remodeling degree of visual plasticity.Flx and BFD promote visual plasticity primarily by inhibiting the response of FD eyes and BFD can promote the response of non-FD eyes.Flx feeding and BFD play synergy effects in remodeling the visual cortex plasticity in adult rats.