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1.
Drug Des Devel Ther ; 14: 3683-3695, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32982175

RESUMO

BACKGROUND: Inflammatory response mediated by microglia plays a key role in cerebral ischemia-reperfusion injury. This study intends to probe the role of lncRNA SNHG4 in regulating the inflammatory response of the microglia during cerebral ischemia reperfusion. MATERIALS AND METHODS: Blood samples and cerebrospinal fluid samples were collected from acute cerebral infarction (ACI) patients and healthy controls. The middle cerebral artery occlusion (MCAO) models were constructed with rats. LPS induction and oxygen-glucose deprivation methods were respectively applied to simulate the activation of microglia in vitro. qRT-PCR was employed to determine the expressions of SNHG4, miR-449c-5p and related inflammatory factors in vivo and in vitro. The inflammatory responses of the microglia subject to the varied expressions of SNHG4 and miR-449c-5p were detected. Luciferase assays were conducted to verify the crosstalk involving SNHG4, miR-449c-5p and STAT6. RESULTS: Compared with the control group, the expression of SNHG4 derived from the samples of ACI patients and the microglia of MCAO group were remarkably down-regulated, but the expression of miR-449c-5p was dramatically up-regulated. Overexpression of SNHG4 and knock-down of miR-449c-5p could inhibit the expression of pro-inflammatory cytokine in the microglia and promote the expression of anti-inflammatory factors. Meanwhile, the phospho-STAT6 was up-regulated, whereas the knock-down of SNHG4 and over-expression of miR-449c-5p in microglia had the opposite effects. Luciferase assay confirmed that SNHG4 could target miR-449c-5p, while miR-449c-5p could target STAT6. CONCLUSION: SNHG4 can regulate STAT6 and repress inflammation by adsorbing miR-449c-5p in microglia during cerebral ischemia-reperfusion injury.


Assuntos
Isquemia Encefálica/metabolismo , Inflamação/metabolismo , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Traumatismo por Reperfusão/metabolismo , Animais , Isquemia Encefálica/patologia , Células Cultivadas , Humanos , Inflamação/patologia , Masculino , MicroRNAs/genética , Microglia/metabolismo , Microglia/patologia , RNA Longo não Codificante/genética , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/patologia , Fator de Transcrição STAT6/genética , Fator de Transcrição STAT6/metabolismo , Regulação para Cima
2.
J Neurosurg Anesthesiol ; 29(3): 211-218, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26859547

RESUMO

BACKGROUND: Control of emergence hypertension and pain is important after craniotomy for monitoring the neurological status. This prospective double-blinded study investigated the hemodynamics after a single bolus of dexmedetomidine (DEX) infusion administered to the patient undergoing craniotomy under general anesthesia, and its effect on emergence hypertension and postsurgical pain. METHODS: Adult patients scheduled for elective surgery for supratentorial tumors were randomized to receive a 10-minute intraoperative DEX infusion of 0.4 µg/kg (small dose, n=43) or 0.8 µg/kg (medium dose, n=46), or normal saline (vehicle control, n=45), ∼60 minutes before the end of anesthesia. RESULTS: A transient increase in the blood pressure associated with DEX was observed; 53.5% and 91.3% of the patients in the small-dose and the medium-dose groups, respectively, required treatment. Emergence mean arterial pressure and heart rates were significantly lower in the DEX groups compared with the control group. Incidence rates of postoperative hypertension in the small-dose (16.3%) and the medium-dose groups (15.2%) were significantly lower relative to that of the control group (35.6%). Patients who received DEX had a lower Verbal Numerical Rating Scale (VNRS) score in the neurosurgical ICU than the control group, and postsurgical pain (VNRS≥4) was lower in the medium-dose group (41.3%) than in the control group (71.1%). No shivering was observed in the medium-dose group, which was significantly less than that of the other 2 groups. CONCLUSIONS: An intraoperative bolus of DEX risks a transient increase in mean arterial pressure, but controls emergence hypertension effectively. Dose-related reductions in postsurgical pain and shivering were observed.


Assuntos
Analgésicos não Narcóticos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Craniotomia/efeitos adversos , Dexmedetomidina/uso terapêutico , Cuidados Intraoperatórios/métodos , Dor Pós-Operatória/prevenção & controle , Neoplasias Supratentoriais/cirurgia , Adulto , Idoso , Analgésicos não Narcóticos/administração & dosagem , Analgésicos não Narcóticos/efeitos adversos , Pressão Arterial/efeitos dos fármacos , Dexmedetomidina/administração & dosagem , Dexmedetomidina/efeitos adversos , Método Duplo-Cego , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipertensão/epidemiologia , Incidência , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória/epidemiologia , Complicações Pós-Operatórias/induzido quimicamente , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos , Estremecimento/efeitos dos fármacos
3.
J Transl Med ; 11: 179, 2013 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-23890086

RESUMO

BACKGROUND: Adipose-derived stromal cells (ADSCs) are a good alternative to multipotent stem cells for regenerative medicine. Low tidal volume (LVT) has proved to be an effective ventilation strategy. However, it is not known if ADSCs and LVT can protect against ventilator-induced lung injury (VILI). This study was aimed to determine the potential of ADSCs and LVT to repair following VILI and to elucidate the mechanisms responsible for this section. METHODS: A total of 72 rats were randomly assigned into group I (sham group, n=18), group II (1 h of high tidal volume-ventilated (HVT) 40 mL/kg to peak airway pressures of approximately 35 cm H2O and 100% oxygen, n=18), group III (1 h of HVT followed by 6 h LVT 6 mL/kg to peak airway pressures of approximately 6 cm H2O and 100% oxygen, n=18) and group IV (1 h of HVT followed by intravenous injection of 5 × 106 ADSCs, n=18). All animals were sacrificed 7 after the experiments lasted for 7 hours. Bronchoalveolar lavage fluid (BALF) was collected and lungs were harvested for analysis. RESULTS: High tidal volume-ventilated (HVT) rats exhibited typical VILI features compared with sham rats. Lung edema, histological lung injury index, concentrations of total protein, total cell counts, number of neutrophils in bronchoalveolar lavage fluid (BALF), tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, IL-10 and transforming growth factor-ß1 in BALF were significantly increased in HVT rats. Additionally, gene and protein levels of Na+ channel subunits, Na-K-ATPase pump activity and alveolar fluid clearance were significantly decreased in HVT rats. All these indices of VILI were significantly improved in rats treated with ADSCs. However, compared with ADSCs treatment, LVT strategy had little therapeutic effect in the present study. CONCLUSION: These results may provide valuable insights into the effects of ADSCs in acute lung injury.


Assuntos
Tecido Adiposo/citologia , Lesão Pulmonar Induzida por Ventilação Mecânica/terapia , Animais , Biomarcadores/metabolismo , Líquido da Lavagem Broncoalveolar , Diferenciação Celular , Membrana Celular/metabolismo , Forma Celular , Quimiocinas/metabolismo , Canais Epiteliais de Sódio/genética , Canais Epiteliais de Sódio/metabolismo , Regulação da Expressão Gênica , Pulmão/enzimologia , Pulmão/patologia , Pulmão/fisiopatologia , Masculino , Infiltração de Neutrófilos , Ratos Sprague-Dawley , ATPase Trocadora de Sódio-Potássio/metabolismo , Células Estromais/transplante , Volume de Ventilação Pulmonar , Transplante Autólogo , Lesão Pulmonar Induzida por Ventilação Mecânica/fisiopatologia
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