涤痰汤对血管性痴呆大鼠兴奋性氨基酸毒性作用相关miRNAs表达的影响研究  

Effect of Ditan Decoction on Expression of miRNAs Related to Excitatory Amino Acid Toxicity for Rats with Vascular Dementia

作　　者：杨怡然 全毅红[1] 郭明星 YANG Yiran;QUAN Yihong;GUO Mingxing(Department of Traditional Chinese Medicine,Wuhan Central Hospital Affiliated to Tongji Medical College,Huazhong University of Science and Technology,Wuhan Hubei 430014,China)

机构地区：[1]华中科技大学同济医学院附属武汉中心医院中医科,湖北武汉430014

出　　处：《四川中医》2022年第5期39-44,共6页Journal of Sichuan of Traditional Chinese Medicine

基　　金：武汉市中心医院学科基金(编号:2021XK027)

摘　　要：目的:探究涤痰汤对血管性痴呆大鼠兴奋性氨基酸毒性作用相关miRNAs表达的影响。方法:72只SD大鼠随机分为6组:对照组、模型组、涤痰汤低、中、高剂量组及易倍申组(阳性对照组),每组12只。除对照组外,其余大鼠采用高脂饲料结合双侧颈动脉结扎法构建血管性痴呆大鼠模型,涤痰汤低、中、高剂量组分别灌胃5、10、20g/kg涤痰汤,易倍申组灌胃2mg/kg易倍申。采用Morris水迷宫实验评价大鼠学习记忆能力,HE染色和TUNEL染色观察海马组织病理学形态变化及细胞凋亡,化学比色法测定大鼠海马组织谷氨酸(Glu)和天门冬氨酸(Asp)含量,定量RT-PCR法检测海马组织miR-107、miR-132及miR-223表达水平。结果:与模型组比较,涤痰汤中、高剂量组和易倍申组大鼠逃避潜伏期、海马组织CA1区细胞凋亡率、Glu、Asp含量、miR-107及miR-132表达水平显著降低,穿越平台次数和miR-223表达水平显著升高(P<0.05),海马组织CA1区病理学变化明显改善,且涤痰汤高剂量组与易倍申组上述指标的比较,无显著性差异(P>0.05)。结论:涤痰汤可提高血管性痴呆大鼠学习记忆能力,减轻海马组织病理损伤并减少神经细胞凋亡,可能通过调节miR-107、miR-132及miR-223水平降低兴奋性氨基酸毒性。Objective:To explore the effect of Ditan Decoction on expression of miRNAs related to excitatory amino acid toxicity for rats with vascular dementia.Methods:Seventy-two SD rats were randomly divided into a controlled group,a model group,a low-dose,a medium-dose and a high-dose Ditan Decoction group,and a Memantine group(positive controlled group),12 cases in each group.Except for the controlled group,rats in the other groups were given high-fat diet combined with bilateral carotid artery ligation to construct models of vascular dementia rats.The low-dose,medium-dose and high-dose Ditan Decoction groups were administered intragastrically with 5,10 and 20 g/kg Ditan Decoction,the Memantine group was administered intragastrically with 2 mg/kg Memantine.The learning and memory ability of rats were evaluated by Morris water maze test.The pathological morphology changes and apoptosis of hippocampus were observed by HE staining and TUNEL staining.The levels of glutamate(Glu)and aspartate(Asp)in hippocampus were detected by chemical colorimetry.The expression levels of miR-107,miR-132 and miR-223 in hippocampus were detected by quantitative RT-PCR.Results:Compared with the model group,escape latency,apoptosis rate in hippocampal CA1 area,levels of Glu and Asp,expressions of miR-107 and miR-132 were significantly decreased,times of crossing platform and miR-223 were significantly increased(P<0.05),and pathological changes in hippocampal CA1 area were significantly improved in the medium-dose and high-dose Ditan Decoction groups,and the Memantine group.There was no significant difference in the above indexes between the high-dose Ditan Decoction group and the Memantine group(P>0.05).Conclusion:Ditan Decoction can improve learning and memory ability of rats with vascular dementia,reduce pathological damage and apoptosis of nerve cells in hippocampus.It may reduce excitatory amino acid toxicity by regulating levels of miR-107,miR-132 and miR-223.

关 键 词：血管性痴呆 涤痰汤 兴奋性氨基酸毒性 miR-107 miR-132 miR-223 

分 类 号：R285.5[医药卫生—中药学]