摘要
目的研究两色金鸡菊总黄酮(total flavones of Coreopsis tinctoria Nutt,CF)改善血管性痴呆(vascular dementia,VD)认知障碍的作用及机制。方法采用改良的双侧颈总动脉永久性结扎法建立VD大鼠模型,实验分为假手术组、模型组、阳性对照药尼麦角林组、CF低、中、高剂量组。给药8周后,使用跳台、避暗及Morris水迷宫评价短期记忆、空间学习记忆能力,采用HE和尼氏染色观察海马组织病理改变;采用ELISA法检测海马组织中TNF-α、IL-1β的含量;采用Western blot法检测海马组织中TLR4、MyD88、NF-κB p65、NF-κB p-p65蛋白表达水平;采用qRT-PCR法检测海马组织中miR-93及TLR4、MyD88、NF-κB p65 mRNA表达水平。结果CF能明显改善VD大鼠短期记忆、空间学习记忆能力;减轻海马组织的病理性损伤;降低海马组织中TNF-α、IL-1β的含量;降低海马组织TLR4、MyD88、NF-κB p-p65的蛋白表达水平;降低海马组织miR-93及TLR4、MyD88 mRNA表达水平。结论CF可能通过抑制miR-93介导的TLR4信号通路降低VD大鼠的神经炎症反应,改善认知障碍。
Aim To investigate the effect of total flavones of Coreopsis tinctoria Nutt(CF)on cognitive impairment in vascular dementia(VD).Methods The VD rat models were established by modified bilateral common carotid arteries ligation method.SD rats were divided into the sham operation group,model group,positive control group(nicergoline),and low,medium,and high dose CF groups.After eight weeks of administration,the short term memory and spatial learning and memory abilities were evaluated by the platform jumping test,dark avoidance test and Morris water maze test.The pathological changes of the hippocampal tissues were inspected by HE and Nissl staining.The contents of TNF-αand IL-1βin the hippocampal were examined by ELISA.The protein expression levels of TLR4,MyD88,NF-κB p65,and p-NF-κB p65 in the hippocampal were detected by Western blot.The mRNA expression levels of miR-93,TLR4,MyD88,and NF-κB p65 in the hippocampal were determined by qRT-PCR.Results CF obviously improved the short term memory and spatial learning and memory abilities of VD rats,and alleviated the pathological damage of the hippocampus.CF also obviously decreased the levels of TNF-αand IL-1β,declined the protein expression levels of TLR4,MyD88,and p-NF-κB p65,and reduced the miR-93,TLR4,and MyD88 mRNA expression in the hippocampus.Conclusion CF has a notable protective effect on the neuroinflammation and cognitive impairments in VD rats by inhibiting the miR-93-mediated TLR4 signaling pathway.
作者
胡梦颖
杨冬梅
朱毅忠
梁钦兰
努尔巴合提·候瓦提
杨晓君
哈木拉提·哈斯木
HU Meng-ying;YANG Dong-mei;ZHU Yi-zhong;LIANG Qin-lan;Nuerbaheti Houwati;YANG Xiao-jun;Hamulati Hasimu(Xinjiang Institute of Materia Medica,Urumqi 830034,China;College of Food Science and Pharmacy,Xinjiang Agricultural University,Urumqi 830052,China;Xinjiang Uygur Autonomous Region Institute for Drug Control,Urumqi 830000,China)
出处
《中国药理学通报》
北大核心
2025年第7期1237-1244,共8页
Chinese Pharmacological Bulletin
基金
国家自然科学基金资助项目(No 82060789)
新疆维吾尔自治区自然科学基金面上项目(No 2022D01A133)。
关键词
两色金鸡菊总黄酮
血管性痴呆
miR-93
TLR4通路
认知障碍
炎症反应
total flavones of Coreopsis tinctoria Nutt
vascular dementia
miR-93
TLR4 signaling pathway
cognitive impairment
inflammatory response
