衰老过程中有氧运动干预对海马突触可塑性及PDE-4基因表达的影响

Effects of Aerobic Exercises on Synaptic Plasticity and Expression of PDE-4 in Hippocampus during the Aging Process of Rats

目的:探讨大鼠衰老过程中进行有氧运动干预对海马突触可塑性及磷酸二酯酶-4(Phos-phodiesterase 4,PDE-4)基因表达水平的影响。方法:雄性SD大鼠,45只,随机分为对照组(C组)、D-半乳糖致衰老模型组(A组)、D-半乳糖致衰老+有氧运动干预组(AE组)。进行6周衰老造模,AE组在造模过程中进行中等负荷游泳运动干预。取材后,尼氏染色观察大鼠海马齿状回(dentate gyrus,DG区)神经元形态结构变化;免疫荧光检测大鼠海马DG区突触素(synaptophysin,Syp)、代谢型谷氨酸受体1(metabo-tropi glutamate receptor 1,m Glu R1)数量和密度的变化;Real-Time PCR及Western Blotting检测大鼠海马磷酸二酯酶-4(Phos-phodiesterase 4,PDE-4)m RNA及蛋白的表达。结果:(1)与C组比,A组大鼠出现精神不振、嗜睡、动作迟缓等衰老体征,海马神经元数量明显减少,排列紊乱,细胞间距增大,胞质中尼氏体着色变浅等;(2)Syp和m Glu R1 IOD值变化趋势一致:A组非常显著性低于C组(P<0.01),AE组非常显著性高于A组(P<0.01)。(3)PDE-4 m RNA及蛋白表达变化趋势一致:A组非常显著性高于C组(P<0.01),AE组非常显著性低于A组(P<0.01)。(4)PDE-4 m RNA与Syp、m Glu R1的IOD值呈显著性负相关(P<0.01,P<0.05)。结论:(1)衰老过程中进行有氧运动干预可以修复海马神经元的形态结构,使Syp和m Glu R1数量和密度保持在一定水平上,以维持突触可塑性,进而改善脑功能,延缓脑衰老;(2)运动可能通过下调PDE-4基因的表达影响脑功能。

Objective To explore the effect of aerobic exercises on synaptic plasticity and expressionof PDE-4 in hippocampus during the aging process of rats. Methods Forty-five adult male Sprague-Dawley rats were randomly divided into a control group（group C）,an D-galactose induced aging group（group A） and an D-galactose induced aging aerobic exercise intervention group（group AE）. Allrats were induced aging for 6 weeks and group AE was given swimming exercise intervention of a mod-erate load simultaneously. Then Nissl＇s staining was conducted to observe the neurons in the dentategyrus（DG）. The immunofluorescence was employed to detect the number and density of synaptophysin（Syp） and metabotropi glutamate receptor 1（m Glu R1）. And the expression level of Phos-phodiesterase4（PDE-4） m RNA and protein was observed using the,real-time PCR and Western blotting. Results Compared with group C,senile signs such as mental retardation,lethargy and tardy movement,significant-ly less neurons in the hippocampus,bigger cell spacing and shallower Nissl body in the cytoplasmwere observed in group A. The integrated optical density（IOD） values of Syp and m Glu R1 in group Adecreased significantly compared to group C（P〈0.01）,while those of group AE were significantly higherthan group A（P〈0.01）. The expression of PDE-4 m RNA and protein in Group A increased significant-ly compared with group C（P〈0.01）,but that of group AE was significantly lower than group A（P〈0.01）. The expression of PDE-4 m RNA was negatively correlated to the IOD value of Syp and m Glu R1（P〈0.01,P〈0.05）. Conclusions The aerobic exercises can improve the morphology of hippocampal neu-rons and keep the number and density of Syp and m Glu R1 at a certain level to maintain the synapticplasticity,so as to improve brain function and delay the aging process. Moreover,exercise may affectbrain function through down-regulating the expression of the PDE-4 gene.