临床传统医学和药理学（英文）2025，Vol.6Issue(1)：93-105,13.DOI:10.1016/j.ctmp.2025.200199
六味地黄丸调节NMDARs/CaMK Ⅱ改善神经精神性狼疮小鼠认知功能障碍研究
Liuwei dihuang pill regulates NMDARs/CaMKⅡ to ameliorate cognitive dysfunction in neuropsychiatric systemic lupus erythematosus mice
摘要
Abstract
Background:As many as 80％of patients with neuropsychiatric lupus develop cognitive dysfunction,yet its diagnosis and treatment are underdeveloped. Objective:This study aimed to investigate the therapeutic effects and underlying mechanisms of Liuwei Dihuang Pill on cognitive dysfunction in mice with neuropsychiatric lupus,utilizing research involving the hippocampal neuronal cell line HT22. Methods:A combination of animal and cellular experiments was employed to investigate the preventive treatment of systemic lupus erythematosus associated with cognitive dysfunction using Liuwei dihuang pill.BALB/c mice were induced with imiquimod and pristane,followed by oral administration of Liuwei Dihuang Pill.Behavioral alterations,levels of anti-dsDNA and anti-ribosomal P protein antibodies,hippocampal indices,changes in hip-pocampal tissue and neurons,and levels of NMDARs and CaMKⅡ in the hippocampus were assessed.Lipopolysac-charide was utilized to induce damage in HT22 cells.The efficacy of serum containing Liuwei Dihuang Pill on these cells was evaluated by observing morphological changes,assessing cell viability,and analyzing protein and mRNA content. Results:Treatment with Liuwei dihuang pill significantly improved levels of autoantibodies,urinary protein,behavioral symptoms,nuclear pyknosis,and apoptosis of hippocampal neurons in mice with neuropsychiatric lupus.Furthermore,there was a notable upregulation in the expression levels of NMDARs and CaMKⅡ.Pretreat-ment with serum containing Liuwei Dihuang Pill markedly increased the survival rate of HT22 cells and elevated both protein and mRNA levels of NMDARs and CaMKⅡ compared to the lipopolysaccharide stimulation group. Conclusion:Liuwei dihuang pill has the potential to improve cognitive function of Pritam and imiquimod induce dysfunction in neuropsychiatric lupus of mice through modulation of CaMKⅡ/NMDAR.关键词
神经精神性系统性红斑狼疮/六味地黄丸/认知功能障碍/N-甲基-D-天冬氨酸受体/钙离子/钙调素依赖的蛋白激酶Ⅱ/HT22细胞Key words
Neuropsychiatric systemic lupus erythematosus/Liuwei dihuang pill/Cognitive dysfunction/N-methyl-D-aspartic acid receptors/Ca2+/calmodulin-dependent protein kinase Ⅱ/HT22 cells引用本文复制引用
张梦格,张晶晶,金艺波,项莎特,钱苏海,刘婷,秦文胜,丁兴红..六味地黄丸调节NMDARs/CaMK Ⅱ改善神经精神性狼疮小鼠认知功能障碍研究[J].临床传统医学和药理学（英文）,2025,6(1):93-105,13.基金项目
This research was supported by Zhejiang Provincial Natural Science Foundation of China under Grant No.ZCLMS25H2705,the National Natural Science Foundation of China(No.81973778),2024 Zhejiang Province College Students Science and Technology Innovation Activity Plan(No.2024R410C067)and the China Postdoctoral Science Founda-tion(2024M762959). （No.81973778）
