目的运用质谱分析、网络药理学和动物实验探讨健脑固本方治疗脑小血管病性认知障碍(cerebral small vessel disease,CSVCI)的作用机制。方法通过质谱分析得出主要活性成分,TCMSP检索其相应作用靶点;通过GeneCards、OMIM数据库检索CSVCI...目的运用质谱分析、网络药理学和动物实验探讨健脑固本方治疗脑小血管病性认知障碍(cerebral small vessel disease,CSVCI)的作用机制。方法通过质谱分析得出主要活性成分,TCMSP检索其相应作用靶点;通过GeneCards、OMIM数据库检索CSVCI疾病靶点;通过String数据库和Cytoscape软件构建药物疾病作用靶点网络可视化;利用DAVID数据库对交集靶点进行GO功能和KEGG信号通路富集分析。结果健脑固本方的有效活性成分有山奈酚、薯蓣皂苷,作用于丝裂原活化蛋白激酶8、蛋白激酶B1等核心靶点,可能通过磷脂酰肌醇3-激酶/蛋白激酶B等信号通路涉及炎症反应。蛋白免疫印迹法检测结果表明健脑固本方抑制Notch-1、RBP-Jκ以及Hes-1的表达。结论本研究初步表明健脑固本方能够通过多靶点、多通路、多途径治疗CSVCI,具体作用机制可能是抑制Notch-1信号通路,进而抑制炎症反应。展开更多
目的系统评价疏血通注射液辅助治疗血管性痴呆(VD)的效果和安全性。方法检索CNKI、SinoMed、万方、维普、PubMed、EMbase、Cochrane Library、Web of Science数据库,纳入疏血通注射液治疗VD的随机对照试验(RCT)。检索时限为建库至2019年...目的系统评价疏血通注射液辅助治疗血管性痴呆(VD)的效果和安全性。方法检索CNKI、SinoMed、万方、维普、PubMed、EMbase、Cochrane Library、Web of Science数据库,纳入疏血通注射液治疗VD的随机对照试验(RCT)。检索时限为建库至2019年5月,由2名研究者独立进行文献检索和提取资料,并对纳入文献进行质量评价,使用RevMan5.3软件进行meta分析。结果纳入8项RCT,共622例患者。meta分析结果显示,与对照组比较,疏血通辅助治疗VD能改善简易精神状态检查量表(MMSE)评分[MD=1.81,95%CI(1.35,2.27),P<0.00001]、日常生活能力量表(ADL)评分[MD=3.23,95%CI(2.03,4.42),P<0.00001],缩短P300潜伏期[MD=23.51,95%CI(16.99,30.03),P<0.00001]和增高波幅[MD=1.40,95%CI(0.71,2.08),P<0.0001]。各研究均未发生严重不良反应。结论疏血通辅助治疗VD能更好地改善患者的认知功能和日常生活能力,且安全性好,无严重不良反应。限于随访时间短、质量偏低、样本量少等因素,仍需开展更多高质量、大样本量、多中心、较长随访时间的RCT。展开更多
OBJECTIVE:To explore the neuroprotective mechanisms of Tongluo Huatan capsule(THC)in a rat model of vascular dementia(VD).METHODS:A rat model of VD was established by repeated clamping of bilateral common carotid arte...OBJECTIVE:To explore the neuroprotective mechanisms of Tongluo Huatan capsule(THC)in a rat model of vascular dementia(VD).METHODS:A rat model of VD was established by repeated clamping of bilateral common carotid arteries with the intraperitoneal injection of sodium nitroprusside solution.VD rats were administered THC,memantine hydrochloride,or distilled water daily for 14 d after operation.Learning and memory abilities were assessed using the step-down passive avoidance test,novel object recognition(NOR)test,and Morris water maze(MWM)test.Pathological changes in the hippocampus were observed through hematoxylin and eosin and Nissl staining.The expression levels of clathrin,RAB5 B,andN-methyl-D-aspartic acid receptor 1(NMDAR1)were measured by immunohistochemistry staining,real-time quantitative polymerase chain reaction and Western blot.RESULTS:Rats in VD group showed impaired learning and memory abilities(step-down passive avoidance,NOR,and MWM)and abnormalities in neuronal morphology(light microscopy)in the hippocampus.The m RNA or protein expression levels of clathrin and RAB5 B were decreased,and NMDAR1 was increased in hippocampal tissues(P<0.05).Administration of THC promoted the learning and memory abilities and the morphological structure of hippocampal neurons in VD rats.Besides,THC enhanced m RNA or protein expression levels of clathrin and RAB5 B,and decreased NMDAR1(P<0.05).CONCLUSION:THC may improve cognitive functions by regulating the endocytosis of NMDA receptors mediated by clathrin.展开更多
文摘目的运用质谱分析、网络药理学和动物实验探讨健脑固本方治疗脑小血管病性认知障碍(cerebral small vessel disease,CSVCI)的作用机制。方法通过质谱分析得出主要活性成分,TCMSP检索其相应作用靶点;通过GeneCards、OMIM数据库检索CSVCI疾病靶点;通过String数据库和Cytoscape软件构建药物疾病作用靶点网络可视化;利用DAVID数据库对交集靶点进行GO功能和KEGG信号通路富集分析。结果健脑固本方的有效活性成分有山奈酚、薯蓣皂苷,作用于丝裂原活化蛋白激酶8、蛋白激酶B1等核心靶点,可能通过磷脂酰肌醇3-激酶/蛋白激酶B等信号通路涉及炎症反应。蛋白免疫印迹法检测结果表明健脑固本方抑制Notch-1、RBP-Jκ以及Hes-1的表达。结论本研究初步表明健脑固本方能够通过多靶点、多通路、多途径治疗CSVCI,具体作用机制可能是抑制Notch-1信号通路,进而抑制炎症反应。
文摘目的系统评价疏血通注射液辅助治疗血管性痴呆(VD)的效果和安全性。方法检索CNKI、SinoMed、万方、维普、PubMed、EMbase、Cochrane Library、Web of Science数据库,纳入疏血通注射液治疗VD的随机对照试验(RCT)。检索时限为建库至2019年5月,由2名研究者独立进行文献检索和提取资料,并对纳入文献进行质量评价,使用RevMan5.3软件进行meta分析。结果纳入8项RCT,共622例患者。meta分析结果显示,与对照组比较,疏血通辅助治疗VD能改善简易精神状态检查量表(MMSE)评分[MD=1.81,95%CI(1.35,2.27),P<0.00001]、日常生活能力量表(ADL)评分[MD=3.23,95%CI(2.03,4.42),P<0.00001],缩短P300潜伏期[MD=23.51,95%CI(16.99,30.03),P<0.00001]和增高波幅[MD=1.40,95%CI(0.71,2.08),P<0.0001]。各研究均未发生严重不良反应。结论疏血通辅助治疗VD能更好地改善患者的认知功能和日常生活能力,且安全性好,无严重不良反应。限于随访时间短、质量偏低、样本量少等因素,仍需开展更多高质量、大样本量、多中心、较长随访时间的RCT。
基金Supported by the National Natural Science Foundation:The Research of Shenzhi Jiannao formula Regulation on Clathrin-mediated NMDA Receptors Endocytosis of Vascular Dementia(No.81673910)。
文摘OBJECTIVE:To explore the neuroprotective mechanisms of Tongluo Huatan capsule(THC)in a rat model of vascular dementia(VD).METHODS:A rat model of VD was established by repeated clamping of bilateral common carotid arteries with the intraperitoneal injection of sodium nitroprusside solution.VD rats were administered THC,memantine hydrochloride,or distilled water daily for 14 d after operation.Learning and memory abilities were assessed using the step-down passive avoidance test,novel object recognition(NOR)test,and Morris water maze(MWM)test.Pathological changes in the hippocampus were observed through hematoxylin and eosin and Nissl staining.The expression levels of clathrin,RAB5 B,andN-methyl-D-aspartic acid receptor 1(NMDAR1)were measured by immunohistochemistry staining,real-time quantitative polymerase chain reaction and Western blot.RESULTS:Rats in VD group showed impaired learning and memory abilities(step-down passive avoidance,NOR,and MWM)and abnormalities in neuronal morphology(light microscopy)in the hippocampus.The m RNA or protein expression levels of clathrin and RAB5 B were decreased,and NMDAR1 was increased in hippocampal tissues(P<0.05).Administration of THC promoted the learning and memory abilities and the morphological structure of hippocampal neurons in VD rats.Besides,THC enhanced m RNA or protein expression levels of clathrin and RAB5 B,and decreased NMDAR1(P<0.05).CONCLUSION:THC may improve cognitive functions by regulating the endocytosis of NMDA receptors mediated by clathrin.
