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1.
Neuroscience ; 356: 193-206, 2017 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-28528966

RESUMO

Nicotinamide phosphoribosyltransferase (NAMPT) is an important neuroprotective factor in cerebral ischemia, and it has been reported that NAMPT inhibitors can aggravate neuronal injury in the acute phase. However, because it is a cytokine, NAMPT participates in many inflammatory diseases in the peripheral system, and its inhibitors have therapeutic effects. Following cerebral ischemia, the peripheral and resident inflammatory and immune cells produce many pro-inflammatory mediators in the ischemic area, which induce neuroinflammation and impair the brain. However, the effects of NAMPT inhibitors in the neuroinflammation after ischemic brain injury remain unknown. Here, we found that FK866, a potent NAMPT inhibitor, decreased the level of TNF-α, NAMPT and IL-6 in the ischemic brain tissue one day after middle-cerebral-artery occlusion and reperfusion (MCAO/R), improved neurological dysfunction, decreased infarct volume and neuronal loss, and inhibited microgliosis and astrogliosis 14days after MCAO/R. The expression of NAMPT protein was induced in Iba1-positive microglia/macrophages in the ischemia core 14days after MCAO/R. In vitro studies show that oxygen-glucose deprivation and recovery (OGD/R) activate microglia. Activated microglia increased the activity of NF-κB, increased the mRNA synthesis of TNF-α, NAMPT and IL-6, and increased the secretion of TNF-α, NAMPT and IL-6. On the other hand, NAMPT can act synergistically with other cytokines and activate microglia. FK866 strongly inhibited these changes and alleviated OGD/R-induced activation of microglia. As such, NAMPT is a crucial determinant of cellular inflammation after cerebral ischemia. NAMPT inhibitors are novel compounds to protect neuronal injury from ischemia via anti-inflammatory effects.


Assuntos
Encéfalo/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Nicotinamida Fosforribosiltransferase/efeitos dos fármacos , Animais , Encéfalo/metabolismo , Modelos Animais de Doenças , Isquemia/tratamento farmacológico , Isquemia/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Microglia/efeitos dos fármacos , NF-kappa B/metabolismo , Neurônios/metabolismo , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo
2.
Shanghai Kou Qiang Yi Xue ; 23(5): 561-5, 2014 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-25543598

RESUMO

PURPOSE: To observe the stimulating effect of pure traditional Chinese medical mouth rinse (PTCMMR) on skin and mucosa and to evaluate the efficacy of PTCMMR on inhibiting and killing oral common bacteria. METHODS: PTCMMR and normal saline (NS) were separately dripped onto 14 five-month rabbits' left and right eyes for 7 days, and were smeared on the left and right side of buttocks, abdomens, back of 10 seven-month guinea pigs (after hair removal) once a day for comparison between the two sides. Five animals were sacrificed after 3 and 7 days of smearing to make pathological sections. Bacterium suspension with Staphylococcus aureus, Escherichia coli, Candida albicans, Pseudomonas aeruginosa and Streptococcus B were dropped to nutrient solution containing different concentrations of PTCMMR or compound Borax solution to observe the growth situation of bacteria. Inhibition zone diameters were measured after 18h of incubation within 37 degrees centigrade incubator. The data was statistically analyzed using SPSS 17.0 software package. RESULTS: There was no obvious change such as redness, dermatitis between rabbits' left eye conjunctiva and the control group. The bacteriostatic and bactericidal effect of anaerobe and aerobe with dropping of PTCMMR was stronger than that of control group. CONCLUSIONS: PTCMMR has no stimulation to skin and mucosa, while it has strong efficacy to inhibit and kill oral common bacteria.


Assuntos
Antibacterianos , Staphylococcus aureus , Animais , Candida albicans , Cobaias , Boca , Mucosa , Pseudomonas aeruginosa , Coelhos
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