小续命汤对光化学法诱导脑卒中小鼠神经炎症反应和血脑屏障损伤的作用及机制OA
Effects and Mechanisms of Xiaoxuming Decoction on Neuroinflammation and Blood-Brain Barrier Injury in the Mouse Model of Ischemic Stroke Induced by the Photochemical Method
目的:本研究旨在探讨小续命汤提取物对脑卒中小鼠神经炎症反应和血脑屏障损伤的作用及机制.方法:应用光化学法诱导缺血性脑卒中小鼠模型.将小鼠随机分为假手术对照组、模型对照组、小续命汤提取物75、150、300 mg/kg组及银杏叶提取物100 mg/kg组.采用改良神经功能缺损评分(mNSS)评估神经功能损伤;抓握力测试和肢体扣合试验检测小鼠肌肉力量;TTC染色法检测脑梗死体积;ELISA法检测脑组织中白介素-1(IL-1β)、IL-6、IL-18、肿瘤坏死因子(TNF-α)、单核细胞趋化蛋白-1(MCP-1)、细胞间黏附分子-1(ICAM-1)的含量;伊文思蓝染色检测血脑屏障完整性;免疫荧光法检测离子钙结合适配器分子1(IBA1)、胶质纤维酸性蛋白(GFAP)、闭合蛋白(Occludin)、紧密连接蛋白-5(Claudin-5)的表达水平.结果:与正常对照组比较,模型对照组小鼠mNSS评分、肢体扣合数量明显增加,脑梗死体积、脑组织IL-1β、IL-6、IL-18、TNF-α、MCP-1、ICAM-1 的含量升高,IBA1和GFAP表达明显升高(P<0.05 或P<0.01),伊文思蓝渗漏量显著升高(P<0.01),梗死周围及梗死核心区域Oc-cludin、Claudin-5 的表达水平明显降低(P<0.05 或P<0.01);与模型对照组比较,小续命汤提取物各组小鼠mNSS评分、肢体扣合数量、脑梗死体积明显降低,脑组织IL-1β、IL-6、IL-18、MCP-1、ICAM-1 含量以及伊文思蓝渗漏量明显降低(P<0.05 或P<0.01),小续命汤提取物75、300 mg/kg组小鼠脑组织TNF-α含量降低(P<0.05),小续命汤提取物各组脑组织GFAP的表达水平降低(P<0.05 或P<0.01),梗死核心区域Occludin的表达水平明显增加,梗死周围与梗死核心区域的Claudin-5 的表达水平明显增加(P<0.05 或P<0.01).结论:小续命汤能够减轻神经炎症反应及保护血脑屏障完整性而发挥抗脑卒中作用.
Objective:To investigate the effects and mechanisms of Xiaoxuming Decoction(小续命汤)extract(XXM)on the neuroinflammation and blood-brain barrier(BBB)injury in the mouse model of ischemic stroke.Meth-ods:A mouse model of ischemic stroke was established by the photochemical method.Mice were randomly grouped as follows:normal control,model control,XXM(75,150,and 300 mg/kg),and Ginkgo biloba extract(100 mg/kg).Neu-rological deficits were assessed via the modified Neurological Severity Score(mNSS).Muscle strength was evaluated through the grip strength test and hind-limb clasping test.Cerebral infarct volume was measured by TTC staining.Levels of interleukin-1β(IL-1β),interleukin-6(IL-6),interleukin-18(IL-18),tumor necrosis factor-α(TNF-α),monocyte chemoattractant protein-1(MCP-1),and intercellular adhesion molecule-1(ICAM-1)in the brain tissue were quantified by enzyme-linked immunosorbent assay(ELISA).Blood-brain barrier integrity was examined via Evans Blue staining.Expression levels of ionized calcium-binding adapter molecule 1(IBA1),glial fibrillary acidic protein(GFAP),OCCLU-DIN,and CLAUDIN-5 were measured by immunofluorescence.Results:Compared with the normal control group,the model control group showed increases in mNSS scores,clasping scores,cerebral infarct volume,levels of IL-1β,IL-6,IL-18,TNF-α,MCP-1,ICAM-1,Iba1,and GFAP(P<0.05 or P<0.01),Evans Blue leakage(P<0.01),while it show-cased down-regulated expression levels of OCCLUDIN and CLAUDIN-5 in the peri-infarct and infarct core regions(P<0.05 or P<0.01).Compared with the model control group,all the XXM groups exhibited reductions in mNSS scores,clasping scores,cerebral infarct volume,levels of IL-1β,IL-6,IL-18,MCP-1,and ICAM-1 in the brain tissue,and Evans Blue leakage(P<0.05 or P<0.01).XXM at 75 mg/kg and 300 mg/kg reduced the TNF-α level in the brain tissue(P<0.05).The expression level of GFAP was down-regulated in all the XXM groups(P<0.05 or P<0.01).The OC-CLUDIN expression in the infarct core region and CLAUDIN-5 expression in both peri-infarct and infarct core regions were up-regulated in all the XXM groups(P<0.05 or P<0.01).Conclusion:Xiaoxuming Decoction exerts anti-stroke effects by alleviating neuroinflammation and protecting the integrity of the blood-brain barrier.
张文芳;刘冬妮;冯琬迪;冯丹虹;徐双;赵闻乐;杜冠华;王月华
中国医学科学院药物研究所 脑血管病新药发现及晶型研究北京市重点实验室,北京 100050中国医学科学院药物研究所 脑血管病新药发现及晶型研究北京市重点实验室,北京 100050中国医学科学院药物研究所 脑血管病新药发现及晶型研究北京市重点实验室,北京 100050中国医学科学院药物研究所 脑血管病新药发现及晶型研究北京市重点实验室,北京 100050中国医学科学院药物研究所 脑血管病新药发现及晶型研究北京市重点实验室,北京 100050中国医学科学院药物研究所 脑血管病新药发现及晶型研究北京市重点实验室,北京 100050中国医学科学院药物研究所 脑血管病新药发现及晶型研究北京市重点实验室,北京 100050中国医学科学院药物研究所 脑血管病新药发现及晶型研究北京市重点实验室,北京 100050
小续命汤缺血性脑卒中神经炎症血脑屏障离子钙结合适配器分子1闭合蛋白胶质纤维酸性蛋白紧密连接蛋白-5
Xiaoxuming DecoctionIschemic strokeNeuroinflammationBlood-brain barrierIonized calcium-binding a-dapter molecule 1(IBA1)OCCUDINGlial fibrillary acidic protein(GFAP)CLAUDIN-5
《中药药理与临床》 2026 (1)
15-21,7
北京市自然科学基金面上项目资助(编号:7232299)中国医学科学院医学与健康科技创新工程项目资助(编号:2021-I2M-1-069).
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