熄风止颤合剂对PSI诱导的帕金森病大鼠黑质超微结构的影响

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目的:观察熄风止颤合剂对帕金森病模型大鼠行为学及脑内黑质多巴胺神经元、神经胶质细胞超微结构的影响。方法:雄性SD大鼠背部皮下注射蛋白酶抑制因子(proteasome inhibitorsI,PSI)造模,造模成功的大鼠随机分为三组:模型组、西药组、中药组。造模完毕四周后,连续3周分别灌胃给予生理盐水、美多巴、熄风止颤合剂。灌胃前、后观察各组大鼠行为学改变。各组大鼠以4%多聚甲醛经心脏灌注固定后取黑质,应用透射电镜观察其神经元、神经胶质细胞超微结构的改变。结果:模型组大鼠出现不自主动作增多、颤抖、卷曲姿态、运动迟缓等表现,中药组上述行为学异常明显减轻。电镜下观察到模型组黑质多巴胺神经元胞膜不连续,核内染色质凝集,线粒体空泡样变或髓样变,高尔基复合体囊泡变,核糖体明显减少。神经胶质细胞核异染色质边集,核周隙增宽,多条胞周有髓神经纤维髓鞘明显剥离。上述病理性改变在中药组较模型组明显轻微。结论:熄风止颤合剂能改善帕金森病模型大鼠的行为学异常、减轻黑质多巴胺神经元和神经胶质细胞的超微病理变化。 OBJECTIVE: To observe the effect of Xifeng Zhichan Mixture on the behavior and brain ultrastructure of dopaminergic neurons and glial cells in Parkinson’s disease model rats. METHODS: Male Sprague-Dawley rats were injected subcutaneously with proteasome inhibitors (PSI). Rats with successful modeling were randomly divided into three groups: model group, western medicine group, and traditional Chinese medicine group. Four weeks after the completion of the modeling, the rats were given intragastric administration of physiological saline, medopa, and Xifeng Zhizheng for 3 consecutive weeks. Before and after intragastric administration, the behavioral changes of rats in each group were observed. All rats were perfused with 4% paraformaldehyde and perfused through the heart to remove substantia nigra. Ultrastructural changes of neurons and glial cells were observed by transmission electron microscopy. RESULTS: The rats in the model group showed increased involuntary movements, tremors, curled posture, and sluggish performance. The above-mentioned behavioral abnormalities in the Chinese medicine group were significantly reduced. Under the electron microscope, the dopaminergic neurons in the model group were observed to have discontinuous membranes, nuclear chromatin condensation, mitochondrial vacuolization or myelination, Golgi complex vesicles changed, and ribosomes significantly decreased. The glial cell nuclear heterochromatin marginal set, the perinuclear space widened, and the myelin sheaths of multiple myelinated nerve fibers were significantly exfoliated. The above pathological changes in the Chinese medicine group were significantly smaller than the model group. Conclusion: Xifeng Zhichan Mixture can improve the abnormal behavior of Parkinson’s disease model rats and reduce the ultrastructural pathological changes of substantia nigra dopaminergic neurons and glial cells.
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