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
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
旨在研究内皮素-1(Endothelin-1,ET-1)对羊驼皮肤黑素细胞(Melanocyte,MC)增殖和黑素合成的影响。本研究中,体外培养正常羊驼皮肤黑素细胞,观察不同浓度ET-1(0、0.1、1、10、100nmol.L-1)对羊驼皮肤黑素细胞增殖、黑素含量、内皮素受体B...旨在研究内皮素-1(Endothelin-1,ET-1)对羊驼皮肤黑素细胞(Melanocyte,MC)增殖和黑素合成的影响。本研究中,体外培养正常羊驼皮肤黑素细胞,观察不同浓度ET-1(0、0.1、1、10、100nmol.L-1)对羊驼皮肤黑素细胞增殖、黑素含量、内皮素受体B(Endothelin recepter B,EDNRB)基因、酪氨酸酶(Tyrosinase,TYR)基因、酪氨酸相关蛋白-1(Tyrosinase related protein 1,TRP-1)基因和表皮黑皮素-1受体(Melanocortin 1receptor,MC1R)基因表达量的影响。结果表明,ET-1处理羊驼皮肤黑素细胞3d后,羊驼皮肤黑素细胞增多,黑素含量、EDNRB、TRP-1和TYR基因表达量都明显增加(P<0.05),以10nmol.L-1组最为显著。ET-1能诱导羊驼皮肤黑素细胞增殖、树突增长,诱导EDNRB、TYR和TRP-1基因表达量增高,使黑素合成增加;同时诱导MC1R基因表达量增高,从而通过α-MSH信号通路对羊驼黑色素的生成产生影响。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.
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.
文摘旨在研究内皮素-1(Endothelin-1,ET-1)对羊驼皮肤黑素细胞(Melanocyte,MC)增殖和黑素合成的影响。本研究中,体外培养正常羊驼皮肤黑素细胞,观察不同浓度ET-1(0、0.1、1、10、100nmol.L-1)对羊驼皮肤黑素细胞增殖、黑素含量、内皮素受体B(Endothelin recepter B,EDNRB)基因、酪氨酸酶(Tyrosinase,TYR)基因、酪氨酸相关蛋白-1(Tyrosinase related protein 1,TRP-1)基因和表皮黑皮素-1受体(Melanocortin 1receptor,MC1R)基因表达量的影响。结果表明,ET-1处理羊驼皮肤黑素细胞3d后,羊驼皮肤黑素细胞增多,黑素含量、EDNRB、TRP-1和TYR基因表达量都明显增加(P<0.05),以10nmol.L-1组最为显著。ET-1能诱导羊驼皮肤黑素细胞增殖、树突增长,诱导EDNRB、TYR和TRP-1基因表达量增高,使黑素合成增加;同时诱导MC1R基因表达量增高,从而通过α-MSH信号通路对羊驼黑色素的生成产生影响。
