加味益气聪明汤对VD大鼠行为学变化及海马神经元突触结构的影响

Influence of the Modified Yiqi Congming Decoction over Behavioral Changes and Synaptic Structure of the Hippocampus of VD Rats

目的观察加味益气聪明汤对血管性痴呆(VD)大鼠行为学变化及海马神经元突触结构的影响。方法将60只实验大鼠随机分为假手术组及手术组,手术组包括模型组、尼莫地平组(简称"对照1组")、复方苁蓉益智胶囊组(简称"对照2组")、加味益气聪明汤组(简称"治疗组")。假手术组只分离出双侧颈总动脉,使之充分暴露,不结扎,手术组采用永久性结扎双侧颈总动脉(2-VO)法制备VD模型,对照1组给予尼莫地平以6.25 mg·kg-1·d-1给药,对照2组给予复方苁蓉益智较囊以0.375 g·kg-1·d-1给药,治疗组给予加味益气聪明汤以14.58 g·kg-1·d-1给药,模型组、假手术组予以2m L/d同体积蒸溜水灌胃,持续30天;选用Morris水迷宫实验检测大鼠的行为学变化,在电镜下观察各组海马区神经元突触超微结构的变化。结果水迷宫实验结果:与假手术组比较,模型组大鼠逃避潜伏期(EL)明显延长(P<0.01),经过有效区及平台的次数显著减少,停留在平台及有效区的时间显著缩短(P<0.01);与模型组比较,对照1组、对照2组、治疗组EL明显缩短(P<0.05或P<0.01),经过平台及有效区的次数增多显著,平台及有效区停留时间明显延长(P<0.05或P<0.01)。电镜结果:假手术组大鼠海马区突触密集度高,结构清晰,突触的各组成成分可被清楚辨认,在突触后致密区可见较深的染色,密度高。模型组突触前膜内的线粒体嵴变得模糊、肿胀明显,突触结构模糊欠清,突触数目减少甚多,在突触后致密区可见较浅的染色,密度不高。与假手术组相比,模型组大鼠海马区突触数目减少明显,突触间隙增宽,突触后致密区染色变浅;与模型组相比,对照1组、对照2组和治疗组大鼠海马区突触显著增多,突触间隙宽度变小,突触后致密区染色变深、突触活性区长度变长;假手术组与对照1组、对照2组、治疗组之间两两比较,上述突触结构参数之间的变化较小。结论加味益气聪明汤能改善VD大鼠海马神经元突触的超微结构,从而改善其学习记忆功能,作用与尼莫地平、复方苁蓉益智胶囊相当。

Objective： To observe the effect of the modified Yiqi Congming Decoction on behavior changes and the synaptic structure of hippocampus neurons of VD （vascular dementia） rats. Method： The 60 laboratory rats were randomly divided into sham - operated and operation group and the latter one includes the model group, the nimodipine （the 1st control group）, the compound Congrong Yizhi Capsule group （the 2nd control group） and the modified Yiqi Congming group （the treatment group）. The models in sham -operated group were just to completely expose carotid artery of both sides but not ligated, while VD models were to permanently conduct a ligation. The 1 st control group received Nimodipine （6.25 mg·kg^-1·d^-1）, the 2nd one the compound Congrong Yizhi Capsule （0. 375 g ·kg^-1·d^-1）, the treatment one the modified Yiqi Congming group （14.58 g ·kg^-1·d^-1） and the model and sham -operated ones were given lavage with same volumed distilled water for 30 days, 2 mL/d. Morris water maze test could be used to check rats＇ behavior change and the electron microscope to observe synaptic ultrastructure changes of hippocampus neurons in all groups. Results ： Water maze experimental results ： Compared with the sham - operated group, rats ＇ EL period obviously extended in model group （ P 〈 0.01 ） and passing numbers and residence time of effective district as well as the platform were markedly reduced and shortened （ P 〈 0.01 ）. Compared with sham - operated group, EL period of the 1 st and 2nd group as well as the treatment group remarkablely shortened （P 〈 0.05 or P 〈 0.01 ） and passing numbers and residence time of effective district as well as the platform were significantly increased and prolonged （ P 〈 0.05 or P 〈 0.01 ）. Electron microscopy results： In sham -operated group, rats＇ hippocampal synapse was highly dense and its structure was clear, its components and deep staining as well as high density in post - synapse dense area clearly identified. In the model group, mitochondrial cristae was becoming blurred and swelling within the presynaptic membrane, its structure lost of clarity, numbers reduced and light staining as well as low density in post - synapse dense area obvoiously seen. Compared with sham - operated group, synaptic numbers in rats＇ hippocampus district visibly reduced, its gap widened and its color in post - synapse dense area lightened in the model group ; Compared with model group, in the 1 st and 2nd group as well as the treatment group, synaptic numbers in rats＇ hippocampus district visibly increased, its gap narrowed, its color in post - synapse dense area darkened and the activity district lengthened. In comparison of two groups among the sham -operated, the 1 st and 2nd as well as the treatment group, the above parameters changed a little. Conclusion ： The modified Yiqi Congming Decoction can improve synaptic ultrastructure of hippocampus neurons in VD rats, thus improving the ability of learning and memory, which is similar to Nimodipine and the compound Congrong Yizhi Capsules.