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1.
China Journal of Chinese Materia Medica ; (24): 1927-1935, 2023.
Artigo em Chinês | WPRIM | ID: wpr-981412

RESUMO

This study aims to explore the neuroprotective mechanism of ginsenoside Re(GS-Re) on drosophila model of Parkinson's disease(PD) induced by rotenone(Rot). To be specific, Rot was used to induce PD in drosophilas. Then the drosophilas were grouped and respectively treated(GS-Re: 0.1, 0.4, 1.6 mmol·L~(-1); L-dopa: 80 μmol·L~(-1)). Life span and crawling ability of drosophilas were determined. The brain antioxidant activity [content of catalase(CAT), malondialdehyde(MDA), reactive oxygen species(ROS), superoxide dismutase(SOD)], dopamine(DA) content, and mitochondrial function [content of adenosine triphosphate(ATP), NADH:ubiquinone oxidoreductase subunit B8(NDUFB8) Ⅰ activity, succinate dehydrogenase complex, subunit B(SDHB) Ⅱ activity] were detected by enzyme-linked immunosorbent assay(ELISA). The number of DA neurons in the brains of drosophilas was measured with the immunofluorescence method. The levels of NDUFB8 Ⅰ, SDHB Ⅱ, cytochrome C(Cyt C), nuclear factor-E2-related factor 2(Nrf2), heme oxygenase-1(HO-1), B-cell lymphoma/leukemia 2(Bcl-2)/Bcl-2-assaciated X protein(Bax), and cleaved caspase-3/caspase-3 in the brain were detected by Western blot. The results showed that model group [475 μmol·L~(-1) Rot(IC_(50))] demonstrated significantly low survival rate, obvious dyskinesia, small number of neurons and low DA content in the brain, high ROS level and MDA content, low content of SOD and CAT, significantly low ATP content, NDUFB8 Ⅰ activity, and SDHB Ⅱ activity, significantly low expression of NDUFB8 Ⅰ, SDHB Ⅱ, and Bcl-2/Bax, large amount of Cyt C released from mitochondria to cytoplasm, low nuclear transfer of Nrf2, and significantly high expression of cleaved caspase-3/caspase-3 compared with the control group. GS-Re(0.1, 0.4, and 1.6 mmol·L~(-1)) significantly improved the survival rate of PD drosophilas, alleviated the dyskinesia, increased DA content, reduced the loss of DA neurons, ROS level, and MDA content in brain, improved content of SOD and CAT and antioxidant activity in brain, maintained mitochondrial homeostasis(significantly increased ATP content and activity of NDUFB8 Ⅰ and SDHB Ⅱ, significantly up-regulated expression of NDUFB8 Ⅰ, SDHB Ⅱ, and Bcl-2/Bax), significantly reduced the expression of Cyt C, increased the nuclear transfer of Nrf2, and down-regulated the expression of cleaved caspase-3/caspase-3. In conclusion, GS-Re can significantly relieve the Rot-induced cerebral neurotoxicity in drosophilas. The mechanism may be that GS-Re activates Keap1-Nrf2-ARE signaling pathway by maintaining mitochondrial homeostasis, improves antioxidant capacity of brain neurons, then inhibits mitochondria-mediated caspase-3 signaling pathway, and the apoptosis of neuronal cells, thereby exerting the neuroprotective effect.


Assuntos
Animais , Espécies Reativas de Oxigênio/metabolismo , Antioxidantes/farmacologia , Estresse Oxidativo , Fator 2 Relacionado a NF-E2/metabolismo , Caspase 3/metabolismo , Doença de Parkinson/genética , Proteína X Associada a bcl-2/metabolismo , Fármacos Neuroprotetores/farmacologia , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Drosophila/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Apoptose , Superóxido Dismutase/metabolismo , Trifosfato de Adenosina/farmacologia
2.
China Journal of Chinese Materia Medica ; (24): 2184-2192, 2023.
Artigo em Chinês | WPRIM | ID: wpr-981349

RESUMO

To investigate the antidepressant mechanism of Shenling Kaixin Granules(SLKX) in treating chronic unpredictable mild stress(CUMS) model rats. Ninety male SD rats were randomly divided into control group, model group, Shugan Jieyu Capsules(110 mg·kg~(-1)) group and SLKX low-(90 mg·kg~(-1)), medium-(180 mg·kg~(-1)), and high-dose(360 mg·kg~(-1)) groups. Depression rat model was replicated by CUMS method. After treatment, the behavioral changes of rats were evaluated by sugar preference, open field, elevated cross maze and forced swimming experiments. The contents of interleukin 1 beta(IL-1β), tumor necrosis factor α(TNF-α), brain-derived neurotrophic factor(BDNF) and 5-hydroxytryptamine(5-HT) in serum were determined by enzyme linked immunosorbent assay(ELISA), and the activities of superoxide dismutase(SOD) and catalase(CAT) in hippocampal CA1 region were also detected. Pathological changes in hippocampal CA1 region were detected by hematoxylin-eosin(HE) staining, and Western blot was used to determine the expression of nerve growth factor(NGF), BDNF, phospho-tyrosine kinase receptor(p-TrkB)/TrkB, phospho-cAMP-response element binding protein(p-CREB)/CREB, nuclear factor E2 related factor 2(Nrf2), heme oxygenase 1(HO-1), B-cell lymphoma-2(Bcl-2)/Bcl-2 associated X protein(Bax) and caspase-3 in hippocampal CA1 region. RESULTS:: showed that compared with the control group, the model group had decreased sugar preference, reduced number of entries and time spent in the center of open field and shortened total distance of movement, reduced number of entries and proportion of time spent in open arm, and increased number and time of immobility in forced swimming experiment. Additionally, the serum contents of IL-1β and TNF-α and the expression of caspase-3 were higher, while the contents of BDNF and 5-HT, the activities of SOD and CAT in hippocampal CA1 region, the expressions of NGF, BDNF, p-TrkB/TrkB, p-CREB/CREB, HO-1 and Bcl-2/Bax, and the Nrf2 nuclear translocation were lower in model group than in control group. Compared with the conditions in model group, the sugar preference, the number of entries and time spent in the center of open, total distance of movement, and the number of entries and proportion of time spent in open arm in treatment groups were increased while the number and time of immobility in forced swimming experiment were decreased; the serum contents of IL-1β and TNF-α and the expression of caspase-3 were down regulated, while the contents of BDNF and 5-HT, the activities of SOD and CAT in hippocampal CA1 region, the expressions of NGF, BDNF, p-TrkB/TrkB, p-CREB/CREB, HO-1, Bcl-2/Bax, and Nrf2 nuclear translocation were enhanced. In conclusion, SLKX might regulate the Nrf2 nucleus translocation by activating BDNF/TrkB/CREB pathway, lower oxidative stress damage in hippocampus, inhibit caspase-3 activity, and reduce apoptosis of hippocampal nerve cells, thereby playing an antidepressant role.


Assuntos
Ratos , Masculino , Animais , Proteína X Associada a bcl-2/metabolismo , Caspase 3/metabolismo , Fator de Crescimento Neural/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismo , Serotonina/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Ratos Sprague-Dawley , Antidepressivos/farmacologia , Hipocampo/metabolismo , Superóxido Dismutase/metabolismo , Açúcares/farmacologia , Depressão/genética , Estresse Psicológico/metabolismo
3.
Journal of Southern Medical University ; (12): 1621-1625, 2016.
Artigo em Chinês | WPRIM | ID: wpr-256548

RESUMO

<p><b>OBJECTIVE</b>To explore the inhibitory effect of estrogen against metastasis of human hepatocellular carcinoma MHCC97H cells and explore the molecular mechanism.</p><p><b>METHODS</b>The inhibitory effect of estrogen on the migration and invasion of MHCC97H cells was evaluated with wound healing assay and Transwell assay. Western blotting was used for investigating the expression of MMP-2, MMP-9, AKT and p-AKT in the cells treated with estrogen.</p><p><b>RESULTS</b>Estrogen treatment significantly inhibited the migration and invasion of MHCC97H cells in a dose-dependent manner. Estrogen significantly down-regulated the protein expressions of MMP-2 and MMP-9 and lowered the phosphorylation level of AKT.</p><p><b>CONCLUSION</b>The anti-metastatic effect of estrogen involves inhibition of MMP-2 and MMP-9 in MHCC97H cells probably by regulating AKT signal pathway.</p>

4.
Chinese Journal of Medical Instrumentation ; (6): 445-446, 2002.
Artigo em Chinês | WPRIM | ID: wpr-344232

RESUMO

This paper introduces the design principles of a penetrator for stomach wall, and its operating method. All the experimental results show that it is a very practical, safe and is a useful medical device while used with the GF-I Model Anastomat in esophagogastro-anastomosis. It may prevent the anastotic stoma complication and may be of great importance in clinical applications.


Assuntos
Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Anastomose Cirúrgica , Métodos , Desenho de Equipamento , Junção Esofagogástrica , Cirurgia Geral , Complicações Pós-Operatórias , Estômago , Cirurgia Geral
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