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Shock ; 35(3): 308-14, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20926985


Various anti-inflammatory agents have been used to treat acute or chronic lung injury-induced pulmonary fibrosis (PF). However, the efficacy of the available treatments is disappointing, and new therapies are urgently needed. In the current study, we investigated the effect of a novel α-melanocyte-stimulating hormone analog, STY39, on bleomycin (BLM)-induced pulmonary inflammation and fibrosis in mice. C57BL/6 mice received an intratracheal injection of BLM before being treated with STY39 (0.625, 1.25, or 2.5 mg/kg, i.p.) once a day for 14 consecutive days. Various parameters, reflecting the inflammatory reaction, metabolism of extracellular matrix, myofibroblast proliferation, and degree of fibrosis in the lung, were evaluated. We found that STY39 significantly improved the survival of mice with lethal BLM-induced lung injury, limited body weight loss and the increase in the lung index, reduced the mRNA expression of types I and III procollagen and the production of hydroxyproline in the lung, diminished myofibroblast proliferation, and ultimately reduced BLM-induced lung damage. Further investigation revealed that, in a dose-dependent manner, STY39 treatment inhibited leukocyte migration into the lung; reduced the production of TNF-α, IL-6, macrophage inflammatory protein 2, and transforming growth factor ß1 in the lung; and altered the ratio of matrix metalloproteinase 1 to tissue inhibitors of metalloproteinase 1. These findings suggest that STY39 attenuates BLM-induced experimental PF by limiting the inflammatory reaction through the inhibition of proinflammatory and profibrosis cytokines and by accelerating the metabolism of extracellular matrix. Therefore, STY39 may be an effective therapy for preventing PF.

Anti-Inflamatórios/uso terapêutico , Bleomicina/toxicidade , Pneumonia/tratamento farmacológico , Fibrose Pulmonar/tratamento farmacológico , alfa-MSH/análogos & derivados , Animais , Imuno-Histoquímica , Interleucina-6/metabolismo , Metaloproteinase 1 da Matriz/metabolismo , Camundongos , Pneumonia/induzido quimicamente , Pneumonia/metabolismo , Reação em Cadeia da Polimerase , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/metabolismo , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
Yao Xue Xue Bao ; 42(3): 269-73, 2007 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-17520825


Binding activity and biologic effect of a novel alpha-melanocyte-stimulating hormone analogue were tested on cells transiently expressing the human melanocortin-1 (MC1), MC3, MC4, and MC5 receptors. The human MC1 and MC5 receptor genes were cloned into the expression vector pcDNA3. 1/ myc-his(-) B. The vectors were transferred to HEK-293 cells by the calcium phosphate method. Stable receptor populations were generated using G418 selection (900 microg x mL(-1)) for subsequent bioassay analysis. K(i) values of the novel alpha-MSH analogue for MC1, MC3, MC4, and MC5 receptors were obtained in competition with [125I]-NDP-MSH for binding studies. The cyclic AMP level was tested by using [3H]-cyclic AMP kit. It is showed that K(i) values of the novel alpha-MSH analogue for MC1, MC3, MC4, and MC5 receptors were (0.159 +/- 0.040), (35.430 +/- 6.743), (19.293 +/- 2.780) and (2.230 +/- 0.670) nmol L(-1), respectively. Its EC50 values for MC1, MC3, MC4, and MC5 receptors were (0.45 +/- 0.07), (7.80 +/- 0.65), (2.55 +/- 0.23) and (0.33 +/- 0.09) nmol L(-1), respectively. In these tests, the novel alpha-MSH analogue is a MC1R and MC5R selective agonist.

Receptores de Melanocortina/metabolismo , alfa-MSH/metabolismo , Sequência de Aminoácidos , Ligação Competitiva , Linhagem Celular , Linhagem Celular Tumoral , AMP Cíclico/metabolismo , Vetores Genéticos , Humanos , Radioisótopos do Iodo , Cinética , Dados de Sequência Molecular , Plasmídeos/genética , Ensaio Radioligante , Receptor Tipo 1 de Melanocortina/agonistas , Receptor Tipo 1 de Melanocortina/genética , Receptor Tipo 1 de Melanocortina/metabolismo , Receptores da Corticotropina/agonistas , Receptores da Corticotropina/genética , Receptores da Corticotropina/metabolismo , Receptores de Melanocortina/agonistas , Receptores de Melanocortina/genética , Transfecção , Trítio , alfa-MSH/análogos & derivados , alfa-MSH/química , alfa-MSH/farmacologia
Wei Sheng Wu Xue Bao ; 45(3): 415-9, 2005 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-15989238


The response of dendritic cells (DCs) plays an essential role in the initiation of immune responses following Mycobacterium tuberculosis (MTB) challenge. Two-dimensional electrophoresis (2-DE) was employed to compare the global protein patterns between human DCs infected and that uninfected with MTB H37Rv ATCC 27294 strains, and 45 protein spots were found to express differentially. Four protein spots which remarkably changed in DCs infected with MTB H37Rv ATCC 27294 strains were measured by matrix assisted laser desorption/ionization tandem time-of-flight (TOF/TOF) mass spectrometry. The data obtained from peptide mass fingerprinting were used in protein database search. Four protein spots in gel were identified as Human Arsenite-stimulated ATPase (hASNA-I), Annexin IV, gamma-actin and Heat shock protein27 (HSP27). These data provide insight into the changed global protein patterns of the DCs after infection and may prove useful for further study in the interaction between MTB and host.

Células Dendríticas/imunologia , Células Dendríticas/microbiologia , Mycobacterium tuberculosis/imunologia , Actinas/análise , Anexina A4/análise , ATPases Transportadoras de Arsenito , Linhagem Celular , Eletroforese em Gel Bidimensional , Proteínas de Choque Térmico/análise , Humanos , Bombas de Íon/análise , Complexos Multienzimáticos/análise , Análise Serial de Proteínas , Proteômica , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
Zhongguo Wei Zhong Bing Ji Jiu Yi Xue ; 16(10): 596-8, 2004 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-15461835


OBJECTIVE: To investigate the effect of alpha-melanocyte stimulating hormone (alpha-MSH) on the apoptosis of the vascular endothelial cells of the lung in acute respiratory distress syndrome (ARDS) reproduced with acute hemorrhagic shock followed by intratracheal lipopolysaccharide (LPS, two-hit model) in rat. METHODS: Ten male Sprague Dawley rats, weighing (33.7+/-2.5) g, were randomly divided into two groups (A and B) with 5 in each group. All rats were anesthesized and ventilated mechanically with fractional concentration of inspired oxygen(FiO(2)) of 0.5, breath rate 100 times/min, tidal volume(V(T)) 12 ml/kg and inspiratory/expiratory ratio (I/E) 1:15. The blood was withdrawn to induce hemorrhagic shock via the carotid artery until blood pressure reached (45+/-5) mm Hg (1 mm Hg=0.133 kPa), which was maintained for 1 hour, and the shed blood and Ringer's lactate in volume equal to the shed blood were reinfused in 2 hours for resuscitation. Afterwards, LPS was given via the tracheal (200 microg/kg, in 500 microl normal saline) to establish the ARDS model. Group A was ARDS control group, group B was alpha-MSH administration group. alpha-MSH was intravenously administrated simultaneously, 3 hours and 6 hours after LPS given, the dosage was 17 mg/kg at each time point. The rats were sacrificed at 9 hours after LPS challenge, and the lung tissue was examined with microscope and electron microscope to observe the pathological changes and apoptosis of the vascular endothelial cells. RESULTS: In ARDS control group, remarkable infiltration of inflammatory cells was found in the alveoli, and the apoptosis of the vascular endothelial cells had developed to late stage. In alpha-MSH treatment group, few inflammatory cells were found in the alveoli, and the apoptosis of the endothelial cells was still in an early stage. CONCLUSION: alpha-MSH could inhibit the apoptosis of the vascular endothelial cells of the lung in the two-hit ARDS in rats. Therefore, it might have a protective effect on the lung after hemorrhagic shock and endotoxin challenge.

Apoptose/efeitos dos fármacos , Células Endoteliais/patologia , Síndrome do Desconforto Respiratório do Adulto/patologia , alfa-MSH/farmacologia , Animais , Modelos Animais de Doenças , Células Endoteliais/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , Pulmão/efeitos dos fármacos , Pulmão/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Síndrome do Desconforto Respiratório do Adulto/etiologia , Choque Hemorrágico/complicações , Choque Hemorrágico/patologia
Acta Pharmacol Sin ; 24(2): 181-6, 2003 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-12546728


AIM: To determine the effects of TCFC (total comarins from the fruits of Cnidium monnieri) on the activity of osteoclasts in vitro. METHODS: Osteoclasts isolated from rat marrow cells were co-cultured with osteoblasts under the 1,25-dihydroxyvitamine D3. The tartrate-resistant acid phosphatase (TRAP) stain was used to identify osteoclast morphology. The activity of TRAP was measured by p-nitrophenyl sodium phosphate assay. The resorption pit area on the bone slices formed by osteoclasts was measured by computer image processing. Calcium concentration in the medium of co-culture of bone slices and osteoclasts was determined by atomic absorption spectra. RESULTS: TCFC 2.5-25 mg/L inhibited osteoclast formation and differentiation. TCFC 0.25-25 mg/L inhibited TRAP activity of osteoclasts and TCFC 25 mg/L decreased the TRAP activity by 26.3 % and 24.1 % after 48 h and 72 h, respectively. TCFC 25 mg/L decreased the osteoclastic bone resorption pit area by 25.05 % and Ca2+ release from bone slices by 41.73 %. CONCLUSION: TCFC reduced the bone lose by decreasing the osteoclast formation, its TRAP activity, and osteoclastic bone resorption.

Reabsorção Óssea , Cnidium , Cumarínicos/farmacologia , Osteoclastos/citologia , Fosfatase Ácida/metabolismo , Animais , Células da Medula Óssea/citologia , Osso e Ossos/metabolismo , Cálcio/metabolismo , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Cnidium/química , Técnicas de Cocultura , Cumarínicos/isolamento & purificação , Frutas/química , Isoenzimas/metabolismo , Osteoblastos/citologia , Osteoclastos/metabolismo , Plantas Medicinais/química , Ratos , Ratos Wistar , Fosfatase Ácida Resistente a Tartarato