Ischemic stroke(IS) is a disease caused by deficiency of blood and oxygen in focal or complete brain,followed by inflammation cascade and other pathological reactions,which finally lead to irreversible damage to the c...Ischemic stroke(IS) is a disease caused by deficiency of blood and oxygen in focal or complete brain,followed by inflammation cascade and other pathological reactions,which finally lead to irreversible damage to the cerebrum.For the inflammation is a key progress at the initiation of ischemia and poststroke,and chemokines work as vital cytokines in inflammation,we focus the roles of chemokines in IS.Studies have shown cerebral ischemia is associated with marked induction of both CXC and CC chemokines which resulting in extensive leukocyte infiltration in the ischemic brain,and neutrophil infiltration may increase cerebral edema inducing injury in the ischemic area.In addition,chemokines also shows other functions such as promote neuroblast migration,hematogenous cell recruitment and functional brain repair.Thus,a similar chemokine ligand/chemokine receptor pair can mediate both beneficial and detrimental effects depending on the window of observation and pathophysiological conditions.This manuscript reviews the studies about chemokine-mediated effects in cerebral ischemia/reperfusion and discusses the potential significance of these interactions in injury and repair of ischemic tissues.We also refer drug development based on the chemokines and clinical applications using chemokines as diagnostic or prognostic biomarkers in ischemic stroke.展开更多
OBJECTIVE To investigate the role of chemokine-like factor 1(CKLF1),a novel C-C chemokine,on brain-blood barrier(BBB)integrity in rat focal cerebral ischemia and reperfusion model.METHODS Antibodies against CKLF1 was ...OBJECTIVE To investigate the role of chemokine-like factor 1(CKLF1),a novel C-C chemokine,on brain-blood barrier(BBB)integrity in rat focal cerebral ischemia and reperfusion model.METHODS Antibodies against CKLF1 was applied to the rightcerebral ventricle immediately after transient middle cerebral artery occlusion.Brain water content,Evans blue leakage and the expression of aquaporin-4(AQP-4),matrix metalloproteinase-9(MMP-9),zonula occludens-1(ZO-1)and occludin were measured.RESULTS After treatment with antiCKLF1 antibody,brain water content and Evans blue leakage in ipsilateral hemisphere were decreased in a dose-dependent manner at 24 h after reperfusion,but not changed in contralateral hemisphere.Anti-CKLF1 antibody reduced the expression of AQP-4 and MMP-9,and upregulated the expression of ZO-1 and Occludin.These results suggest that CKLF1 is involved in BBB disruption after reperfusion.CONCLUSION Inhibition of CKLF1 protects against cerebral ischemia by maintaining BBB integrity,possibly via inhibiting the expression of AQP-4 and MMP-9,and increasing the expression of tight junction protein.展开更多
消栓通络方临床上主治脑血栓引起的精神呆滞、言语迟涩等症状,疗效显著,但其作用机制尚不明确。本文通过搜集消栓通络方中的化学成分和治疗脑卒中相关靶点,获得1251个化学成分和10个脑卒中相关靶点,采用朴素贝叶斯和递归分割等机器学习...消栓通络方临床上主治脑血栓引起的精神呆滞、言语迟涩等症状,疗效显著,但其作用机制尚不明确。本文通过搜集消栓通络方中的化学成分和治疗脑卒中相关靶点,获得1251个化学成分和10个脑卒中相关靶点,采用朴素贝叶斯和递归分割等机器学习算法,基于分子指纹和分子描述符,结合分子对接方法,构建了脑卒中10个相关靶点的18个化合物-靶点相互作用预测模型。应用这些模型预测了消栓通络方的活性化学成分及其作用靶点,发现了153个潜在活性化学成分,其中22个可以与2个以上脑卒中药物靶点相互作用。在此基础上,利用网络构建专业软件,构建了化学成分-靶点网络,并通过Gene-Ontology(GO)富集分析,确证了靶点重要的生物过程,如凝血(blood coagulation)、血管生成正调控(positive regulation of angiogenesis)和离子转运正调控(positive regulation of ion transport)等。在此基础上,构建了靶点-通路网络。本研究利用机器学习、分子对接、虚拟筛选、数据挖掘及网络构建等技术方法,探索并部分揭示了消栓通络方抗脑卒中的活性物质基础及其化学成分-靶点-通路的网络作用机制,为消栓通络方的深入研究提供重要信息依据。展开更多
基金National Natural Science Foundation of China(U140222181373997+6 种基金81573640815736368160331581603316)Beijing Natural Science Foundation (7161011)CAMS Innovation Fundfor Medical Sciences (CIFMS) ( 2016-I2M-1-004)Key Research and Development Project of Hun
文摘Ischemic stroke(IS) is a disease caused by deficiency of blood and oxygen in focal or complete brain,followed by inflammation cascade and other pathological reactions,which finally lead to irreversible damage to the cerebrum.For the inflammation is a key progress at the initiation of ischemia and poststroke,and chemokines work as vital cytokines in inflammation,we focus the roles of chemokines in IS.Studies have shown cerebral ischemia is associated with marked induction of both CXC and CC chemokines which resulting in extensive leukocyte infiltration in the ischemic brain,and neutrophil infiltration may increase cerebral edema inducing injury in the ischemic area.In addition,chemokines also shows other functions such as promote neuroblast migration,hematogenous cell recruitment and functional brain repair.Thus,a similar chemokine ligand/chemokine receptor pair can mediate both beneficial and detrimental effects depending on the window of observation and pathophysiological conditions.This manuscript reviews the studies about chemokine-mediated effects in cerebral ischemia/reperfusion and discusses the potential significance of these interactions in injury and repair of ischemic tissues.We also refer drug development based on the chemokines and clinical applications using chemokines as diagnostic or prognostic biomarkers in ischemic stroke.
基金The project supported by National Natural Science Foundation of China(81302760)the Chinese Postdoctoral Science Foundation Project(2013M542510)
文摘OBJECTIVE To investigate the role of chemokine-like factor 1(CKLF1),a novel C-C chemokine,on brain-blood barrier(BBB)integrity in rat focal cerebral ischemia and reperfusion model.METHODS Antibodies against CKLF1 was applied to the rightcerebral ventricle immediately after transient middle cerebral artery occlusion.Brain water content,Evans blue leakage and the expression of aquaporin-4(AQP-4),matrix metalloproteinase-9(MMP-9),zonula occludens-1(ZO-1)and occludin were measured.RESULTS After treatment with antiCKLF1 antibody,brain water content and Evans blue leakage in ipsilateral hemisphere were decreased in a dose-dependent manner at 24 h after reperfusion,but not changed in contralateral hemisphere.Anti-CKLF1 antibody reduced the expression of AQP-4 and MMP-9,and upregulated the expression of ZO-1 and Occludin.These results suggest that CKLF1 is involved in BBB disruption after reperfusion.CONCLUSION Inhibition of CKLF1 protects against cerebral ischemia by maintaining BBB integrity,possibly via inhibiting the expression of AQP-4 and MMP-9,and increasing the expression of tight junction protein.
文摘消栓通络方临床上主治脑血栓引起的精神呆滞、言语迟涩等症状,疗效显著,但其作用机制尚不明确。本文通过搜集消栓通络方中的化学成分和治疗脑卒中相关靶点,获得1251个化学成分和10个脑卒中相关靶点,采用朴素贝叶斯和递归分割等机器学习算法,基于分子指纹和分子描述符,结合分子对接方法,构建了脑卒中10个相关靶点的18个化合物-靶点相互作用预测模型。应用这些模型预测了消栓通络方的活性化学成分及其作用靶点,发现了153个潜在活性化学成分,其中22个可以与2个以上脑卒中药物靶点相互作用。在此基础上,利用网络构建专业软件,构建了化学成分-靶点网络,并通过Gene-Ontology(GO)富集分析,确证了靶点重要的生物过程,如凝血(blood coagulation)、血管生成正调控(positive regulation of angiogenesis)和离子转运正调控(positive regulation of ion transport)等。在此基础上,构建了靶点-通路网络。本研究利用机器学习、分子对接、虚拟筛选、数据挖掘及网络构建等技术方法,探索并部分揭示了消栓通络方抗脑卒中的活性物质基础及其化学成分-靶点-通路的网络作用机制,为消栓通络方的深入研究提供重要信息依据。
