S14G-humanin对β-淀粉样蛋白所致小鼠海马CA1区长时程增强抑制效应的影响  

Effect of S14G-humanin on long-term potentiation inhibition induced by β-amyloid protein in mouse hippocampal CA1 region

作　　者：赵波[1] 苗建亭[1] 李柱一[1] 刘睿[1] 赵振宇[2] 陈雪峰[2] 张巍[1] 

机构地区：[1]第四军医大学唐都医院神经内科,710038 [2]第四军医大学唐都医院功能性脑疾病研究所,710038

出　　处：《中国神经免疫学和神经病学杂志》2010年第2期123-126,共4页Chinese Journal of Neuroimmunology and Neurology

基　　金：国家自然科学基金资助项目(30801215;30870842)

摘　　要：目的探讨S14G-humanin(HNG)对β-淀粉样蛋白(Aβ)在突触网络水平导致的海马CA1区突触长时程增强(LTP)抑制作用的影响。方法常规制备小鼠海马脑片并分为健康对照组、Aβ25-35(400 nmol/L)组、HNG(400 nmol/L)组、Aβ25-35 400 nmol/L+HNG 100 nmol/L组(Aβ25-35+HNG 100组)、Aβ25-35 400nmol/L+HNG 200 nmol/L组(Aβ25-35+HNG 200组)、Aβ25-35 400 nmol/L+HNG 400 nmol/L组(Aβ25-35+HNG 400组)6组,各组分别使用含相应药物的人工脑脊液(ACSF)持续灌流1 h,健康对照组仅用ACSF灌流。应用平面多电极阵列技术记录各组LTP情况。结果 (1)Aβ25-35组LTP幅度值为(115.8±2.3)%,与健康对照组[(169.5±8.0)%]相比有统计学差异(P<0.01)。Aβ25-35+HNG 100组[(118.3±6.1)%]与Aβ25-35组相比无统计学差异(P>0.05),Aβ25-35+HNG 200组[(136.8±5.9)%]、Aβ25-35+HNG 400组[(165.4±5.4)%]及HNG组[(168.2±1.7)%]与Aβ25-35组相比均有统计学差异(分别P<0.05、P<0.01、P<0.01)。Aβ25-35+HNG 100组、Aβ25-35+HNG 200组与健康对照组比较均有统计学差异(分别P<0.01、P<0.05);Aβ25-35+HNG 400组及HNG组与健康对照组比较均无统计学差异(均P>0.05)。(2)各组记录到LTP的电极数,Aβ25-35组为(3.7±2.1)个,Aβ25-35+HNG 100组为(7.5±2.2)个,均少于健康对照组[(14.2±1.2)个,均P<0.01)];Aβ25-35+HNG 200组为(11.7±2.3)个,Aβ25-35+HNG 400组为(12.6±1.7)个,HNG组为(14.5±1.2)个,与Aβ25-35组相比均有统计学差异(分别P<0.05、P<0.01、P<0.01),与健康对照组相比均无统计学差异(均P>0.05)。Aβ25-35+HNG 100组与Aβ25-35组比较无统计学差异(P>0.05),Aβ25-35+HNG 200组、Aβ25-35+HNG 400组及HNG组与Aβ25-35组比较均有统计学差异(分别P<0.05、P<0.01、P<0.01)。结论 HNG能够有效减轻Aβ25-35对海马CA1区LTP的抑制作用,提示HNG对Aβ25-35所致的突触可塑性损害具有保护作用。Objective To investigate the effect of S14G-humanin （HNG） on the inhibition of long-term potentiation （LTP） induced by β3-amyloid protein （Aβ） in hippoeampal CA1 region at the level of synaptic network with planar multi-electrode arrays. Methods Conventional method was used to prepare the mouse hippocampal slices and they were divided into control group, Aβ25-35 （400 nmol/L） group, HNG （400 nmol/ L） group, Aβ25-35 400 nmol/L ＋ HNG 100 nmol/L group, Aβ25-35 400 nmol/L＋ HNG 200 nmol/L group （Aβ25-35 ＋ HNG 200 group） and Aβ25-35 400 nmol/L ＋ HNG 400 nmol/L group （Aβ25-35＋ HNG 400 group）. The control group was perfused with artificial cerebrospinal fluid （ACSF） for 1 h. The other groups were perfumed with ACSF containing different drugs. Planar multi-electrode arrays was used to record the LTP of all groups. Results （1） In contrast to the control group [ （169.5 ± 8.0）%] [percentage of the baseline excitatory postsynaptic potnetial （EPSP） slope], Aβ25-35 group significantly reduced the slope of LTP [ （115.8 ± 2.3）%, P〈 0.01 ]. Aβ25-35 ＋ H NG 100 group [ （ 118.3 ± 6.1 ） % ] shows no significant difference （P〉 0.05 ） compare with Aβ25-35 group. Aβ25-35 group shows significant difference in comparison with Aβ25-35 ＋ HNG 200 group [ （β6.8±5.9）%, P〈0.05], Aβ25-35＋HNG 400 group [ （165.4±5.4）G, P〈0.01] and HNG group [ （168.2± 1.7）%, P〈0.01]. Compared with normal controls, both Aβ25-35 ＋ HNG 100 group （P〈 0.01） and Aβ25-35 ＋ HNG 200 group （P 〈 0.05） showed significant difference （P 〈 0.01, P 〈 0.05, respectively）, but A125-35＋ HNG 400 group and HNG group showed no significant difference （P〉0. 05）. （2） Compared with normal controls （14.2±1.2）, the propagation of LTP was significantly reduced in Aβ25-35 group （3.7±2.1, P〈0.01） and Aβ25-35＋HNG 100 group （7.5±2.2, P〈0.01）. The propagation of LTP in Aβ25-35＋HNG 200 group （11.7±2.3） was significantly

关 键 词：S14G-humanin 淀粉样Β蛋白 平面多电极阵列 海马 长时程增强 

分 类 号：R742.89[医药卫生—神经病学与精神病学]