反复热性惊厥对大鼠海马区神经元超微结构及突触形态学影响的研究

Study of hippocampal neuronal ultrastructures and synaptic morphology in rats with repeated febrile seizures.

【目的】观察热性惊厥大鼠脑海马区神经元、细胞器超微结构及神经突触形态学参数变化,探讨热性惊厥性学习记忆损害的可能机制。【方法】36只21日龄雄性SD大鼠均分为热性惊厥组(febrile seizures group,FS)、发热对照组(febrile control group,FG)及正常对照组(normal control group,NG)。采用热水浴法建立热性惊厥大鼠模型,应用透射电镜分别观察海马CA1区神经元、细胞器的病理超微结构改变和神经突触参数变化特征。【结果】FS组大鼠脑海马区出现显著病理超微结构改变。FS组在神经元变性坏死(χ2=44.61,P<0.005)、线粒体肿胀(χ2=8 9.5 4,P<0.005)、内质网脱颗粒(χ2=36.96,P<0.005)及高尔基体扩张(χ2=18.82,P<0.05)等方面较对照组程度严重,差异有非常显著性。三组在突触后致密物质厚度[FS、FG、NG组分别为(66.43±19.46)nm(、89.91±25.48)nm及(96.18±26.13)nm,F=11.23,P<0.01]、突触活性带长度[FS、FG、NG组分别为(347.87±124.65)nm(、392.01±147.55)nm及(395.63±149.77)nm,F=10.84,P<0.01]、突触界面曲率[FS、FG、NG组分别为(1.0926±0.1247)、(1.1788±0.1933)及(1.1549±0.1831),F=3.19,P<0.05]及突触间隙[FS、FG、NG组分别为(46.21±6.32)nm(、32.55±5.12)nm及(29.67±5.08)nm,F=7.14,P<0.01]等方面的差异有显著性,提示FS组大鼠脑海马CA1区突触后致密物质厚度减小、突触活性带长度缩短、突触界面曲率下降及突触间隙增宽。FS组与对照组在突触数密度(F=2.46,P>0.05)及面密度(F=1.87,P>0.05)方面差异无显著性。【结论】反复热性惊厥发作可导致大鼠脑海马区严重的神经元和细胞器超微病理改变,同时伴有神经突触可塑性变化,推测热性惊厥性学习记忆损害与以上病理改变有关。

[Objective] To explore the possible mechanism of learning and memory impairment in rats with febrile seizures by observing the ultrastructural pathologic changes of hippocampal neurons and organelles, and the features of synaptic morphological parameters. [Methods] Thirty and six 21-day-old male Sprague-Dawley rats were randomly divided into febrile seizures group（FS）,febrile control group（FG） and normal control group（NG）. Febrile seizures was induced by hyperthermal bath. Transmission electron microscope were used to examine the uhrastructural pathologic changes of neurons and organelles, and the features of synaptic morphological parameters in hippocampal CA1 area. [Results] Severe uhrastructural pathologic changes were found in hippocampal CA1 area of rats with febrile seizures. The changes of neuro- nal degeneration and necrosis（ zx^2 = 44.61 ,P〈0. 005）, mitochondria swelling（ x^2 = 89.54, P〈0. 005）, polyribosomes disaggregation from endoplasmic reticulums（ z ^2= 36.96, P〈0. 005）, and golgiosomes dilation（ x^2 = 18. 82, P〈0. 005） in FS group were more significantly severe than those of the control groups. Compared with the control groups, FS group showed significant decreases of postsynaptic density thickness[ （66.43±19.46）nm for FS, （89.91±25.48）nm for FG, and （96.18±26.13）nm for NG,F= 11.23,P〈0.01], synaptic active zone length[ （347.87± 124.65）nm for FS, （392.01±147.55）nm for FG,and（395.63±149.77）nm for NG,F= 10.84,P〈0.01], and synaptic interface curvature[ （1. 0926±0. 1247） for FS, （1. 1788±0. 1933） for FG, and（1. 1549±0. 1831） for NG, F=3. 19,P〈0.05], as well as significant in creases of synaptic cleft[ （46.21±6.32）nm for FS, （32.55±5.12）nm for FG, and（29.67±5.08）nm for NG,F= 7. 14,P 〈0.013. In addition, FS group showed no significant differences in synaptic numeric density （F = 2. 46, P〉 0.05 ） and synaptic surface density （F=I. 87,P〉0.05） as compared with the control groups. [Conclusion] Multiple febrile seizures could result in severe ultrastructural pathologic chandes of neurons and organells, as well as the significant synaptic plasticity in hippocampal areas of rats with febrile seizures.