Early Intervention of Gastrodin Improved Motor Learning in Diabetic Rats Through Ameliorating Vascular Dysfunction
Early Intervention of Gastrodin Improved Motor Learning in Diabetic Rats Through Ameliorating Vascular Dysfunction
复制标题
天麻素的早期干预通过改善血管功能障碍改善糖尿病大鼠的运动学习
DOI：
10.1007/s11064-020-03039-6
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发表时间：
2020-05-15
影响因子：
4.4
通讯作者：
Zou, Ying-Ying
中科院分区：
文献类型：
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作者：
Zhang, Fan;Deng, Cheng-Kun;Zou, Ying-Ying
糖尿病认知功能障碍的机制尚不清楚。最近，研究表明小脑参与认知。此外，糖尿病引起的小脑改变与血管变化有关。因此，我们的目的是探讨血管功能在糖尿病引起的小脑损害和运动学习障碍中的作用。通过单次注射链脲佐菌素在Sprague-Dawley大鼠中诱导1型糖尿病。通过平衡木行走测试和平衡木平衡测试评估运动学习能力。HE染色和尼氏染色观察小脑的病理变化。通过抗caspase-3免疫染色评价细胞凋亡。蛋白质表达通过蛋白质印迹和双重免疫荧光进行评估。我们的研究结果表明，糖尿病大鼠的运动学习能力受损，再加上浦肯野细胞受损和小脑毛细血管密度下降。此外，小脑中神经元型NOS、诱导型NOS、内皮型NOS、总一氧化氮、血管内皮生长因子及其同源受体Flk-1的蛋白表达均降低。天麻素治疗可改善神经元损伤，恢复相关因子的蛋白表达。提示小脑血管功能障碍和NO信号转导障碍可能是糖尿病认知功能损害的早期表现，天麻素干预可改善糖尿病认知功能损害。
The mechanism of cognitive dysfunction in diabetes is still unclear. Recently, studies have shown that the cerebellum is involved in cognition. Furthermore, diabetes-induced cerebellar alterations is related to vascular changes. Therefore, we aimed to explore the roles of vascular function in diabetes-induced cerebellar damage and motor learning deficits. Type 1 diabetes was induced by a single injection of streptozotocin in Sprague–Dawley rats. Motor learning was assessed by beam walk test and beam balance test. The pathological changes of the cerebellum were assessed by Hematoxylin and eosin staining and Nissl staining. Apoptosis was evaluated by anti-caspase-3 immunostaining. Protein expression was evaluated by western blotting and double immunofluorescence. Our results have shown that motor learning was impaired in diabetic rats, coupled with damaged Purkinje cells and decreased capillary density in the cerebellum. In addition, the protein expression of neuronal NOS, inducible NOS, endothelial NOS, total nitric oxide, vascular endothelial growth factor and its cognate receptor Flk-1 was decreased in the cerebellum. Gastrodin treatment ameliorated neuronal damage and restored protein expression of relevant factors. Arising from the above, it is suggested that vascular dysfunction and NO signaling deficits in the cerebellum may be the underlying mechanism of early manifestations of cognitive impairment in diabetes, which could be ameliorated by gastrodin intervention.