中国中医药信息杂志2025，Vol.32Issue(4)：120-127,8.DOI:10.19879/j.cnki.1005-5304.202404457
丹龙醒脑方对血管性痴呆大鼠海马组织小胶质细胞活化及HMGB1/RAGE/NF-κB通路的影响
Effects of Danlong Xingnao Prescription on the Activation of Microglial Cells in Hippocampal Region and HMGB1/RAGE/NF-κB Pathway in Vascular Dementia Model Rats
摘要
Abstract
Objective To investigate the effects of Danlong Xingnao Prescription on learning and memory ability and microglia activation in rats with vascular dementia(VD)based on HMGB1/RAGE/NF-κB pathway.Methods Ten rats were randomly selected from 72 rats as a sham-operation group.The remaining rats were treated with modified bilateral common carotid artery ligation method to prepare the VD model.The 50 successful model rats were randomly divided into model group,nimodipine group(10.8 mg/kg)and Danlong Xingnao Prescription low-,medium-and high-dosage groups(3.7,7.4,14.8 g/kg),with 10 rats in each group.The administration groups were given relevant solution for gavage,the sham-operation group and model group were given the same amount of normal saline for consecutive 28 d.Morris water maze test was performed to evaluate learning and memory abilities of rats,the morphology in the hippocampus were observed by HE staining,the contents of interleukin(IL)-1β,IL-6 and tumor necrosis factor(TNF)-α in hippocampal tissue were detect by ELISA,RT-PCR was used to detect high mobility group protein B1(HMGB1),receptor of advanced glycation end product(RAGE),nuclear factor(NF)-κB p65 and regulatory RNase-1(Regnase-1)mRNA expression in hippocampal tissue,immunohistochemistry and Western blot were used to detect the protein expressions of ion calcium binding adapter molecule 1(Iba1),HMGB1,RAGE,NF-κB p65 and Regnase-1 in hippocampal tissue.Results Compared with the sham-operation group,the escape latency of rats was prolonged,and the number of crossings through the original platform was increased in the model group(P<0.01),the pyramidal cells in the hippocampus were reduced and irregularly shaped,with unclear cell and nuclear membranes,and a significant number of necrotic neurons were visible,the contents of IL-1β,IL-6 and TNF-α in hippocampal tissue increased(P<0.01),the mRNA expressions of HMGB1,RAGE and NF-κB p65 in hippocampal tissue increased(P<0.01),while the mRNA expression of Regnase-1 decreased(P<0.01),the protein expressions of Iba1,HMGB1,RAGE and NF-κB p65 increased(P<0.01),while the protein expression of Regnase-1 decreased(P<0.01).Compared with the model group,the escape latency of rats was shortened in Danlong Xingnao Prescription groups,the number of crossings through the original platform was reduced(P<0.05,P<0.01),the neuronal structure of hippocampal tissue was significantly improved,the number of necrotic neurons was reduced,and the contents of IL-1β,IL-6 and TNF-α in hippocampal tissue reduced(P<0.05,P<0.01),the mRNA expressions of HMGB1,RAGE and NF-κB p65 in hippocampal tissue decreased,the mRNA expression of Regnase-1 increased(P<0.05,P<0.01),the protein expression of Iba1,HMGB1,RAGE and NF-κB p65 decreased,the protein expression of Regnase-1 increased(P<0.05,P<0.01).Conclusion Danlong Xingnao Prescription can improve the learning and memory ability of VD rats,and its mechanism may be related to inhibiting the activation of HMGB1/RAGE/NF-κB pathway and increasing Regnase-1 expression,thereby inhibiting the activation of microglia.关键词
丹龙醒脑方/血管性痴呆/学习记忆/HMGB1/RAGE/NF-κB通路/小胶质细胞/大鼠Key words
Danlong Xingnao Prescription/vascular dementia/learning and memory/HMGB1/RAGE/NF-κB pathway/microglia/rats分类
医药卫生引用本文复制引用
张运辉,杨梦琳,周小青,伍大华,刘霞,秦建设,黄玉静..丹龙醒脑方对血管性痴呆大鼠海马组织小胶质细胞活化及HMGB1/RAGE/NF-κB通路的影响[J].中国中医药信息杂志,2025,32(4):120-127,8.基金项目
国家自然科学基金面上项目(81874462) （81874462）
重庆市教委科学技术研究计划项目(KJQN202302708) （KJQN202302708）
重庆市中医药传承创新团队(三峡库区道地药材保护与利用多学科交叉创新团队)(2022年) （三峡库区道地药材保护与利用多学科交叉创新团队）
重庆市中医药重点学科(中医基础理论)建设项目(2021年) （中医基础理论）
重庆市乡村振兴对口帮扶科技项目(2023TIAD-ZXX0010) （2023TIAD-ZXX0010）
重庆三峡医药高等专科学校校级创新团队-中医药防治呼吸和老年病团队(TIG202302) （TIG202302）
万州区博士直通车项目(wzst20230415) （wzst20230415）
重庆三峡医药高等专科学校自然科学校级重点项目(2019XZZ005) （2019XZZ005）
