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1.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 47(5): 660-664, 2016 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-28598075

RESUMO

OBJECTIVES: To investigate the protective effect of Tanshinone IIA (TSA) on oxygen-glucose deprivation and reperfusion (OGD/R) injury of BV-2 cell and its NLRP3 inflammatory signaling pathway. METHODS: The highest expression level of NLPR3 in BV-2 cells was detected by Western blot after oxygen-glucose deprivation (OGD) for 3 h and reperfusion for different time, to determine the most suitable reperfusion time. Cell viability of TSA (0-2.5 ug/mL) treatment was detected by CCK8 assay to determine the maximum effect concentration of TSA. In TSA 0 (also called OGD group), 0.5, 1.0, 2.0 ug/mL groups, expression levels of NLRP3 and caspase-1 were detected by Western blot, while IL-1ß and IL-18 in culture medium of those groups were detected by ELISA assay. RESULTS: The highest expression level of NLRP3 came to 12 h of reperfusion. The maximum effective concentration of TSA was 2.0 ug/mL. The expression levels of NLRP3, caspase-1, IL-1ß and IL-18 decreased with the increase of TSA concentration. CONCLUSIONS: TSA can inhibit the expression of protein and cytokines of NLRP3 inflammatory signaling pathway in OGD/R BV-2 cells, which may be one of the molecular mechanisms of the protective effect of TSA on OGD/R cells.


Assuntos
Abietanos/farmacologia , Microglia/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Traumatismo por Reperfusão/metabolismo , Transdução de Sinais , Animais , Linhagem Celular , Citocinas/metabolismo , Glucose , Camundongos , Oxigênio
2.
Neuromolecular Med ; 16(1): 191-204, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24197755

RESUMO

Inhalational anesthetic preconditioning can induce neuroprotective effects, and the notch signaling pathway plays an important role in neural progenitor cell differentiation and the inflammatory response after central nervous system injury. This study evaluated whether the neuroprotective effect of isoflurane preconditioning is mediated by the activation of the notch signaling pathway. Mice were divided into two groups consisting of those that did or did not receive preconditioning with isoflurane. The expression levels of notch-1, notch intracellular domain (NICD), and hairy and enhancer of split (HES-1) were measured in mice subjected to transient global cerebral ischemia-reperfusion injury. The notch signaling inhibitor DAPT and conditional notch-RBP-J knockout mice were used to investigate the mechanisms of isoflurane preconditioning-induced neuroprotection. Immunohistochemical staining, real-time polymerase chain reaction assays, and Western blotting were performed. Isoflurane preconditioning induced neuroprotection against global cerebral ischemia. Preconditioning up-regulated the expression of notch-1, HES-1, and NICD after ischemic-reperfusion. However, these molecules were down-regulated at 72 h after ischemic-reperfusion. The inhibition of notch signaling activity by DAPT significantly attenuated the isoflurane preconditioning-induced neuroprotection, and similar results were obtained using notch knockout mice. Our results demonstrate that the neuroprotective effects of isoflurane preconditioning are mediated by the pre-activation of the notch signaling pathway.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/fisiologia , Proteínas de Homeodomínio/fisiologia , Ataque Isquêmico Transitório/tratamento farmacológico , Isoflurano/uso terapêutico , Proteínas do Tecido Nervoso/fisiologia , Fármacos Neuroprotetores/uso terapêutico , Pré-Medicação , Receptor Notch1/fisiologia , Traumatismo por Reperfusão/prevenção & controle , Transdução de Sinais/efeitos dos fármacos , Animais , Apoptose , Ataxia/etiologia , Ataxia/prevenção & controle , Fatores de Transcrição Hélice-Alça-Hélice Básicos/biossíntese , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Região CA1 Hipocampal/irrigação sanguínea , Região CA1 Hipocampal/patologia , Artéria Carótida Primitiva , Circulação Cerebrovascular/efeitos dos fármacos , Dipeptídeos/farmacologia , Avaliação Pré-Clínica de Medicamentos , Proteínas de Homeodomínio/biossíntese , Proteínas de Homeodomínio/genética , Ataque Isquêmico Transitório/fisiopatologia , Isoflurano/administração & dosagem , Isoflurano/farmacologia , Ligadura , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas do Tecido Nervoso/biossíntese , Proteínas do Tecido Nervoso/genética , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/farmacologia , Nitrogênio/administração & dosagem , Nitrogênio/farmacologia , Estrutura Terciária de Proteína , Distribuição Aleatória , Receptor Notch1/antagonistas & inibidores , Receptor Notch1/biossíntese , Receptor Notch1/deficiência , Receptor Notch1/genética , Traumatismo por Reperfusão/etiologia , Transdução de Sinais/fisiologia , Fatores de Transcrição HES-1 , Regulação para Cima
3.
Acta Pharmacol Sin ; 33(1): 11-8, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22158106

RESUMO

AIM: To investigate the neuroprotective effect of glycyrrhizin (Gly) against the ischemic injury of rat spinal cord and the possible role of the nuclear protein high-mobility group box 1 (HMGB1) in the process. METHODS: Male Sprague-Dawley rats were subjected to 45 min aortic occlusion to induce transient lumbar spinal cord ischemia. The motor functions of the animals were assessed according to the modified Tarlov scale. The animals were sacrificed 72 h after reperfusion and the lumbar spinal cord segment (L2-L4) was taken out for histopathological examination and Western blotting analysis. Serum inflammatory cytokine and HMGB1 levels were analyzed using ELISA. RESULTS: Gly (6 mg/kg) administered intravenously 30 min before inducing the transient lumbar spinal cord ischemia significantly improved the hind-limb motor function scores, and reduced the number of apoptotic neurons, which was accompanied by reduced levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) in the plasma and injured spinal cord. Moreover, the serum HMGB1 level correlated well with the serum TNF-α, IL-1ß and IL-6 levels during the time period of reperfusion. CONCLUSION: The results suggest that Gly can attenuate the transient spinal cord ischemic injury in rats via reducing inflammatory cytokines and inhibiting the release of HMGB1.


Assuntos
Citocinas/sangue , Ácido Glicirrízico/uso terapêutico , Proteína HMGB1/sangue , Fármacos Neuroprotetores/uso terapêutico , Traumatismos da Medula Espinal/tratamento farmacológico , Animais , Citocinas/imunologia , Ácido Glicirrízico/farmacologia , Humanos , Vértebras Lombares , Masculino , Atividade Motora/efeitos dos fármacos , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Fármacos Neuroprotetores/farmacologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Traumatismos da Medula Espinal/patologia
4.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 27(8): 865-7, 2011 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-21806882

RESUMO

AIM: To explore the protective mechanism of LPS pretreatment in a rat model of cerebral ischemia-reperfusion injury. METHODS: Sixty-six male Spraque-Dawley rats were randomly divided into a sham group (n=22), a control group (n=22) and a LPS group (n=22).The control group and the LPS group were subjected to focal cerebral isehmia induced by middle cerebral artery occlusion (MCAO) for 2 hours. The LPS group was pretreated with LPS for five consecutive days with the last pretreatment at 24 hours before the surgery, while the control group and the sham group were pretreated similarly with normal saline. Seventy-two hours after reperfusion, the rats were examined for neurological behavior scores and then killed to measure the infarct volumes and the brain levels of TNF-α, IL-1ß, IL-6 and IL-10. RESULTS: The brain levels of LRG and IL-10 in the LPS group were significantly higher than those in the control group, while obvious decrease of TNF-α, IL-1ß and IL-6 was observed in the brains of the LPS group. Accordingly, the neurological behavior scores in the LPS group were better than those in the control group, whereas the infarct volumes in the LPS group were significantly smaller than those in the control group (P<0.05). CONCLUSION: LPS pretreatment has neuroprotective effect, which involves LRG upregulation and interference in the dynamic balance of inflammatory reactions.


Assuntos
Encéfalo/metabolismo , Encéfalo/patologia , Endotoxinas/metabolismo , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Modelos Animais de Doenças , Endotoxinas/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Mediadores da Inflamação/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/fisiopatologia , Traumatismo por Reperfusão/prevenção & controle
5.
Anesthesiology ; 114(2): 340-54, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21239965

RESUMO

BACKGROUND: Recent studies suggest that the novel neuropeptide orexin-A may play an essential role during neuronal damage. However, the function of orexin-A during brain ischemia remains unclear. Recently, hypoxia-inducible factor-1α (HIF-1α) was shown to be activated by orexin-A. The aim of the current study is to test the hypothesis that administration of exogenous orexin-A can attenuate ischemia-reperfusion injury through the facilitation of HIF-1α expression. METHODS: Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion for 120 min. Rats were treated with different doses of orexin-A or vehicle before the ischemia and at the onset of reperfusion. To investigate the action of HIF-1α in the neuroprotective effects of orexin-A, the HIF-1α inhibitor YC-1 was used alone or combined with orexin-A. Neurologic deficit scores and infarct volume were assessed. Brains were harvested for immunohistochemical staining and western blot analysis. RESULTS: Orexin-A significantly ameliorated neurologic deficit scores and reduced infarct volume after cerebral ischemia reperfusion. Administration of 30 µg/kg orexin-A showed optimal neuroprotective effects. This effect was still present 7 days after reperfusion. Furthermore, orexin-A decreased the number of apoptotic cells and significantly enhanced HIF-1α expression after cerebral ischemia reperfusion. Moreover, the facilitation of HIF-1α expression was accompanied with inhibition of von Hippel-Lindau expression. Administration of HIF-1α inhibitor suppressed the increase of HIF-1α and reversed the neuroprotective effects of orexin-A. CONCLUSIONS: Orexin-A has a neuroprotective effect against cerebral ischemia-reperfusion injury. These effects may be mediated through the HIF-1α pathway.


Assuntos
Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/farmacologia , Neuropeptídeos/farmacologia , Fármacos Neuroprotetores/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Análise de Variância , Animais , Apoptose/efeitos dos fármacos , Western Blotting , Isquemia Encefálica/metabolismo , Isquemia Encefálica/prevenção & controle , Subunidade alfa do Fator 1 Induzível por Hipóxia/efeitos dos fármacos , Marcação In Situ das Extremidades Cortadas , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Masculino , Neuropeptídeos/metabolismo , Fármacos Neuroprotetores/metabolismo , Neurotransmissores/metabolismo , Neurotransmissores/farmacologia , Orexinas , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo
6.
Anesth Analg ; 111(2): 506-14, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20610552

RESUMO

BACKGROUND: In this study, we sought to clarify the role of inhibiting ubiquitin-conjugated protein aggregation in the formation of a neuroprotective effect after isoflurane preconditioning using a transient global cerebral ischemia-reperfusion injury mouse model. METHODS: C57BL/6 mice were randomly assigned to 3 groups (isoflurane preconditioning [IsoPC] group, control [Con] group, and sham group, n = 24 in each group). Mice in the IsoPC group and sham group were placed in a chamber and pretreated with isoflurane (1.2% isoflurane, 98% O(2), 1 hour/day) for 5 days. Mice in the Con group were placed in the same chamber but pretreated with oxygen only (98% O(2), 2% N(2), 1 hour/day) for 5 days. Twenty-four hours after the last preconditioning day, bilateral common carotid artery occlusion was performed as a model of global cerebral ischemia for 20 minutes in the IsoPC group and Con group. The total motor scores, number of viable neurons in the CA1 region of the hippocampus, and expression levels of conjugated ubiquitin or free ubiquitin were assessed by neurological assessment, immunohistochemistry, and Western blotting (at 24 and 72 hours) after reperfusion, respectively. RESULTS: The total motor scores in the IsoPC group were better than the Con group (P < 0.05). Morphological observations showed that the IsoPC group had better neuron structure than in the Con group. The numbers of viable neurons in the CA1 region were significantly increased by isoflurane preconditioning compared with those in the Con group (P < 0.05). The numbers of TUNEL-positive neurons in the CA1 region were significantly decreased after isoflurane preconditioning. The density of conjugated ubiquitin staining in the CA1 region of the IsoPC group was significantly lower than in the Con group (P < 0.05) and the expression of conjugated ubiquitin in the IsoPC group was lower than in the Con group (P < 0.05). CONCLUSION: Inhibition of ubiquitin-conjugated protein aggregation may have an essential role in inducing cerebral ischemic tolerance by isoflurane preconditioning in a transient global cerebral ischemia-reperfusion injury mouse model.


Assuntos
Região CA1 Hipocampal/efeitos dos fármacos , Ataque Isquêmico Transitório/tratamento farmacológico , Isoflurano/administração & dosagem , Fármacos Neuroprotetores/administração & dosagem , Processamento de Proteína Pós-Traducional , Células Piramidais/efeitos dos fármacos , Traumatismo por Reperfusão/prevenção & controle , Proteínas Ubiquitinadas/metabolismo , Animais , Apoptose/efeitos dos fármacos , Western Blotting , Região CA1 Hipocampal/irrigação sanguínea , Região CA1 Hipocampal/metabolismo , Região CA1 Hipocampal/patologia , Sobrevivência Celular , Circulação Cerebrovascular/efeitos dos fármacos , Modelos Animais de Doenças , Regulação para Baixo , Esquema de Medicação , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Ataque Isquêmico Transitório/metabolismo , Ataque Isquêmico Transitório/fisiopatologia , Fluxometria por Laser-Doppler , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Atividade Motora/efeitos dos fármacos , Exame Neurológico , Células Piramidais/metabolismo , Células Piramidais/patologia , Fluxo Sanguíneo Regional/efeitos dos fármacos , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/fisiopatologia , Fatores de Tempo , Ubiquitinação
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