中国中西医结合杂志2026，Vol.46Issue(2)：184-191,8.DOI:10.7661/j.cjim.20250704.248
解毒祛瘀滋阴方对醋酸泼尼松致MRL/lpr小鼠海马神经元损伤增效减毒作用
Jiedu Quyu Ziyin Prescription Enhances Therapeutic Efficacy and Attenuates Toxicity in Prednisone Acetate-Induced Hippocampal Neuronal Damage in MRL/lpr Mice
摘要
Abstract
Objective To elucidate the mechanism of hippocampal neuronal damage induced by prednisone acetate(PA)in MRL/lpr mice and to study the efficacy-enhancing and toxicity-attenuating effects of Jiedu Quyu Ziyin Prescription(JP)in mitigating hippocampal neuronal damage.Methods Twenty-four 7-week-old MRL/Ipr lupus-prone mice were acclimatized for 1 week and then randomly divided into the following groups(n=8 per group):model group,PA group(5 mg/kg),PA+JP group(5 mg/kg PA+15.6 g/kg JP),with MRL/MpJ mice serving as the control group.Mice in the control and model groups received double-distilled water(0.1 mL/10 g body weight)by gastrogavage for 4 successive weeks.Hippocampal neuronal injury was assessed by in vivo induction of long-term potentiation(LTP),with the relative amplitude of population spikes(PS)following high-frequency stimulation(HFS)serving as an indicator of LTP induction.Morris water maze tests were conducted to evaluate learning and memory performance.RT-qPCR and Western Blot were performed to detect the gene and protein expressions of N-methyl-D-aspartate receptor subtype 2A(NMDAR2A),a key marker of LTP induction,in hippocampal tissues.The levels of the neurotransmitters glutamate(Glu)and γ-aminobutyric acid(GABA)in hippocampal tissues were quantified by ELISA.HT22 cells in the logarithmic growth phase were divided into three groups:control group(hippocampal neuronal cell model group),PA group,and PA+JP group.Each group was treated with 100 μL of PA solution at various concentrations for 24 h,after which cell viability was assessed using the MTT assay to determine the optimal PA concentration.Cellular morphology was observed under a microscope.The levels of Glu and GABA in the cell supernatant were measured by ELISA,while NMDAR2A expression in HT22 cells was analyzed by Western Blot and RT-qPCR.Results Compared with the model group,both PA and PA+JP interventions significantly reduced the spleen and lymph node indices and anti-dsDNA levels(P＜0.01).The PA group exhibited a decreased relative PS amplitude after HFS(P＜0.01),prolonged escape latency(P＜0.01),reduced platform crossings,and shortened swimming distances in the target quadrant(P＜0.05,P＜0.01).Additionally,hippocampal expressions of Glu,GABA,and NMDAR2A(protein and mRNA)were down-regulated(P＜0.01).Compared with the control group(hippocampal neuronal cell model group),the PA group showed reduced HT22 cell viability(P＜0.01)and decreased expressions of Glu and NMDAR2A(protein and mRNA)(P＜0.05).The PA+JP group demonstrated an increased relative PS amplitude(P＜0.01),longer swimming distances in the target quadrant(P＜0.05),and up-regulated hippocampal NMDAR2A expression(protein and mRNA)(P＜0.01,P＜0.05),as compared with the PA group.Furthermore,HT22 cell viability was enhanced(P＜0.05),GABA expression was up-regulated(P＜0.01),and NMDAR2A expression(protein and mRNA)was up-regulated(P＜0.05).Conclusion The combined treatment of JP and PA improved glucocorticoid-induced hippocampal neuronal damage by regulating the expressions of related neurotransmitters in hippocampal tissue,thereby exerting therapeutic effect enhancing and toxicity attenuating in the treatment of systemic lupus erythematosus.关键词
系统性红斑狼疮/解毒祛瘀滋阴方/醋酸泼尼松/神经元损伤/中药复方Key words
systemic lupus erythematosus/Jiedu Quyu Ziyin Prescription/prednisone acetate/neuronal damage/Chinese herbal compound引用本文复制引用
许小芬,胡超,陈凌峰,王尧,丁兴红..解毒祛瘀滋阴方对醋酸泼尼松致MRL/lpr小鼠海马神经元损伤增效减毒作用[J].中国中西医结合杂志,2026,46(2):184-191,8.基金项目
国家自然科学基金资助项目(No.81973778) （No.81973778）
