Vascular etiology is the second most prevalent cause of cognitive impairment globally.Endothelin-1,which is produced and secreted by endothelial cells and astrocytes,is implicated in the pathogenesis of stroke.However...Vascular etiology is the second most prevalent cause of cognitive impairment globally.Endothelin-1,which is produced and secreted by endothelial cells and astrocytes,is implicated in the pathogenesis of stroke.However,the way in which changes in astrocytic endothelin-1 lead to poststroke cognitive deficits following transient middle cerebral artery occlusion is not well understood.Here,using mice in which astrocytic endothelin-1 was overexpressed,we found that the selective overexpression of endothelin-1 by astrocytic cells led to ischemic stroke-related dementia(1 hour of ischemia;7 days,28 days,or 3 months of reperfusion).We also revealed that astrocytic endothelin-1 overexpression contributed to the role of neural stem cell proliferation but impaired neurogenesis in the dentate gyrus of the hippocampus after middle cerebral artery occlusion.Comprehensive proteome profiles and western blot analysis confirmed that levels of glial fibrillary acidic protein and peroxiredoxin 6,which were differentially expressed in the brain,were significantly increased in mice with astrocytic endothelin-1 overexpression in comparison with wild-type mice 28 days after ischemic stroke.Moreover,the levels of the enriched differentially expressed proteins were closely related to lipid metabolism,as indicated by Kyoto Encyclopedia of Genes and Genomes pathway analysis.Liquid chromatography-mass spectrometry nontargeted metabolite profiling of brain tissues showed that astrocytic endothelin-1 overexpression altered lipid metabolism products such as glycerol phosphatidylcholine,sphingomyelin,and phosphatidic acid.Overall,this study demonstrates that astrocytic endothelin-1 overexpression can impair hippocampal neurogenesis and that it is correlated with lipid metabolism in poststroke cognitive dysfunction.展开更多
目的:探讨针灸在颈性眩晕治疗中的临床效果及对中医症状积分、C反应蛋白(C-reactive protein,CRP)、内皮素-1(Endothelin-1,ET-1)、降钙素基因相关肽(Calcitonin gene related peptide,CGRP)水平及生活质量的影响。方法:选取我院2020年...目的:探讨针灸在颈性眩晕治疗中的临床效果及对中医症状积分、C反应蛋白(C-reactive protein,CRP)、内皮素-1(Endothelin-1,ET-1)、降钙素基因相关肽(Calcitonin gene related peptide,CGRP)水平及生活质量的影响。方法:选取我院2020年3月至2021年11月期间收治的80例颈性眩晕患者作为研究对象。用随机数字法将其分对照组和观察组,每组各40例。对照组接受整脊法治疗,观察组在对照组基础上再接受针灸治疗。分析比较两组的疗效、中医症状积分、CRP、ET-1、CGRP水平以及生活质量。结果:观察组疗效显著高于对照组(P<0.05)。治疗前,两组的中医症状积分比较无显著差异(P>0.05)。治疗后,观察组视物模糊、头痛积分均显著低于对照组(P<0.05)。治疗前,两组的CRP、ET-1、CGRP指标水平比较无显著差异(P>0.05)。治疗后,观察组的CRP、ET-1均显著高于对照组,CGRP水平显著低于对照组(P<0.05)。治疗前,两组的SF-36评分比较无显著差异(P>0.05)。治疗后,观察组的SF-35评分显著高于对照组(P<0.05)。结论:颈性眩晕患者在接受整脊法治疗基础上,再给予针灸治疗,能提高临床疗效,改善CRP、ET-1、CGRP指标水平和临床症状,提高患者的生活质量。展开更多
Objective:To assess whether Veronicastrum axillare(V.axillare)can ameliorate ethanol-induced gastric mucosal lesions in rats,reduce the production of pro-inflammatory cytokines,suppress apoptosis and improve local mic...Objective:To assess whether Veronicastrum axillare(V.axillare)can ameliorate ethanol-induced gastric mucosal lesions in rats,reduce the production of pro-inflammatory cytokines,suppress apoptosis and improve local microcirculation disturbances.Methods:Totally 48 male Sprague-Dawley rats were randomly divided into six groups,eight rats in each group.Rats in the normal group and the model group were administered with 0.9%normal saline respectively.Rats in the positive group and ranitidine group were administered with 0.18%ranitidine suspension by intragastric administration respectively.Those in the high dose V.axillare group,the medium dose V.axillare group and the low dose V.axillare group were administrated with V.axillare at the daily dose of 2.8 g/kg,1.4 g/kg and 0.7 g/kg by intragastric administration.Gastric mucosal lesions were produced by intragastric administration of absolute ethanol.Water extract of V.axillare was successively injected for 14 d and last day was injected 1 h before ethanol administration.Gastric mucosal ulcer index and ulcer inhibitory rate were counted by improved Guth methods.The tissue sections were made for pathological histology analysis.Also,we measured the concentrations of tumor necrosis factor-α(TNF-α)and endothelin-1(ET-1)in gastric mucosal,as an index of the pro-inflammatory cytokines,apoptosis and local microcirculation.Besides,the mRNA contents of TNF-αand ET-1 were measured to verify effects on gene expression by real-time fluorescent quantitative PCR.Results:Water extract of V.axillare significantly ameliorated the gastric mucosal lesions induced by ethanol administration(P【0.01).Pro-inflammatory cytokines,TNF-a and ET-1 were increased after ethanol administration and significantly reduced by water extract of V.axillare.The expressions of TNF-αand ET-1 mRNA were also be inhibited by water extract of V.axillare.Conclusion:Current evidences show water extract of V.axillare is effective for defending against ethanol-induced gastric mucosal lesions,significantly inhibiting the production of proinflammatory cytokines and the expressions of TNF-αand ET-1 mRNA,which may be useful for inhibiting apoptosis and improving local microcirculation.展开更多
基金financially supported by the National Natural Science Foundation of China,No.81303115,81774042 (both to XC)the Pearl River S&T Nova Program of Guangzhou,No.201806010025 (to XC)+3 种基金the Specialty Program of Guangdong Province Hospital of Chinese Medicine of China,No.YN2018ZD07 (to XC)the Natural Science Foundatior of Guangdong Province of China,No.2023A1515012174 (to JL)the Science and Technology Program of Guangzhou of China,No.20210201 0268 (to XC),20210201 0339 (to JS)Guangdong Provincial Key Laboratory of Research on Emergency in TCM,Nos.2018-75,2019-140 (to JS)
文摘Vascular etiology is the second most prevalent cause of cognitive impairment globally.Endothelin-1,which is produced and secreted by endothelial cells and astrocytes,is implicated in the pathogenesis of stroke.However,the way in which changes in astrocytic endothelin-1 lead to poststroke cognitive deficits following transient middle cerebral artery occlusion is not well understood.Here,using mice in which astrocytic endothelin-1 was overexpressed,we found that the selective overexpression of endothelin-1 by astrocytic cells led to ischemic stroke-related dementia(1 hour of ischemia;7 days,28 days,or 3 months of reperfusion).We also revealed that astrocytic endothelin-1 overexpression contributed to the role of neural stem cell proliferation but impaired neurogenesis in the dentate gyrus of the hippocampus after middle cerebral artery occlusion.Comprehensive proteome profiles and western blot analysis confirmed that levels of glial fibrillary acidic protein and peroxiredoxin 6,which were differentially expressed in the brain,were significantly increased in mice with astrocytic endothelin-1 overexpression in comparison with wild-type mice 28 days after ischemic stroke.Moreover,the levels of the enriched differentially expressed proteins were closely related to lipid metabolism,as indicated by Kyoto Encyclopedia of Genes and Genomes pathway analysis.Liquid chromatography-mass spectrometry nontargeted metabolite profiling of brain tissues showed that astrocytic endothelin-1 overexpression altered lipid metabolism products such as glycerol phosphatidylcholine,sphingomyelin,and phosphatidic acid.Overall,this study demonstrates that astrocytic endothelin-1 overexpression can impair hippocampal neurogenesis and that it is correlated with lipid metabolism in poststroke cognitive dysfunction.
文摘目的:探讨针灸在颈性眩晕治疗中的临床效果及对中医症状积分、C反应蛋白(C-reactive protein,CRP)、内皮素-1(Endothelin-1,ET-1)、降钙素基因相关肽(Calcitonin gene related peptide,CGRP)水平及生活质量的影响。方法:选取我院2020年3月至2021年11月期间收治的80例颈性眩晕患者作为研究对象。用随机数字法将其分对照组和观察组,每组各40例。对照组接受整脊法治疗,观察组在对照组基础上再接受针灸治疗。分析比较两组的疗效、中医症状积分、CRP、ET-1、CGRP水平以及生活质量。结果:观察组疗效显著高于对照组(P<0.05)。治疗前,两组的中医症状积分比较无显著差异(P>0.05)。治疗后,观察组视物模糊、头痛积分均显著低于对照组(P<0.05)。治疗前,两组的CRP、ET-1、CGRP指标水平比较无显著差异(P>0.05)。治疗后,观察组的CRP、ET-1均显著高于对照组,CGRP水平显著低于对照组(P<0.05)。治疗前,两组的SF-36评分比较无显著差异(P>0.05)。治疗后,观察组的SF-35评分显著高于对照组(P<0.05)。结论:颈性眩晕患者在接受整脊法治疗基础上,再给予针灸治疗,能提高临床疗效,改善CRP、ET-1、CGRP指标水平和临床症状,提高患者的生活质量。
基金Supported by Traditional Chinese Medicine Project of Zhejiang Province(Grant No.2010ZB025)Founds of Zhejiang Provincial Educational Department(Grant No.Y201121241)
文摘Objective:To assess whether Veronicastrum axillare(V.axillare)can ameliorate ethanol-induced gastric mucosal lesions in rats,reduce the production of pro-inflammatory cytokines,suppress apoptosis and improve local microcirculation disturbances.Methods:Totally 48 male Sprague-Dawley rats were randomly divided into six groups,eight rats in each group.Rats in the normal group and the model group were administered with 0.9%normal saline respectively.Rats in the positive group and ranitidine group were administered with 0.18%ranitidine suspension by intragastric administration respectively.Those in the high dose V.axillare group,the medium dose V.axillare group and the low dose V.axillare group were administrated with V.axillare at the daily dose of 2.8 g/kg,1.4 g/kg and 0.7 g/kg by intragastric administration.Gastric mucosal lesions were produced by intragastric administration of absolute ethanol.Water extract of V.axillare was successively injected for 14 d and last day was injected 1 h before ethanol administration.Gastric mucosal ulcer index and ulcer inhibitory rate were counted by improved Guth methods.The tissue sections were made for pathological histology analysis.Also,we measured the concentrations of tumor necrosis factor-α(TNF-α)and endothelin-1(ET-1)in gastric mucosal,as an index of the pro-inflammatory cytokines,apoptosis and local microcirculation.Besides,the mRNA contents of TNF-αand ET-1 were measured to verify effects on gene expression by real-time fluorescent quantitative PCR.Results:Water extract of V.axillare significantly ameliorated the gastric mucosal lesions induced by ethanol administration(P【0.01).Pro-inflammatory cytokines,TNF-a and ET-1 were increased after ethanol administration and significantly reduced by water extract of V.axillare.The expressions of TNF-αand ET-1 mRNA were also be inhibited by water extract of V.axillare.Conclusion:Current evidences show water extract of V.axillare is effective for defending against ethanol-induced gastric mucosal lesions,significantly inhibiting the production of proinflammatory cytokines and the expressions of TNF-αand ET-1 mRNA,which may be useful for inhibiting apoptosis and improving local microcirculation.