RESUMEN
This study investigated the role of perivascular adipose tissue (PVAT) in the beneficial effects of andrographolide on vascular reactivity in endotoxaemic rats. After being challenged by lipopolysaccharide (4 mg/kg intraperitoneally), the rats were treated with andrographolide (1 mg/kg intraperitoneally). The response to phenylephrine of aortic rings with or without PVAT was recorded. Vascular relaxing effect of PVAT was determined by bioassay experiments. Inducible nitric oxide synthase (iNOS) in aortic PVAT was tested by Western blot, immunofluorescence, and quantitative polymerase chain reaction. Lipopolysaccharide injection lowered the contraction force induced by phenylephrine in aortic rings with or without PVAT and andrographolide treatment reversed these effects. In bioassay experiments, transferring bathing solution incubated with a PVAT+ ring to a PVAT- ring induced relaxation in the recipient. This relaxing effect of PVAT from endotoxaemic rats was more potent than the rats treated with vehicles. Andrographolide treatment decreased the relaxing effect of PVAT in endotoxaemic rats. The levels of iNOS protein and messenger RNA in PVAT were significantly higher in endotoxaemic rats than in the rats treated with vehicles. Andrographolide treatment decreased PVAT iNOS protein and messenger RNA levels in endotoxaemic rats. Our results suggest that andrographolide restores vascular reactivity in endotoxaemic rats by downregulation of iNOS in PVAT.
Asunto(s)
Tejido Adiposo Blanco/efectos de los fármacos , Antiinflamatorios no Esteroideos/uso terapéutico , Modelos Animales de Enfermedad , Diterpenos/uso terapéutico , Regulación hacia Abajo/efectos de los fármacos , Endotoxemia/tratamiento farmacológico , Óxido Nítrico Sintasa de Tipo II/antagonistas & inhibidores , Tejido Adiposo Blanco/inmunología , Tejido Adiposo Blanco/metabolismo , Tejido Adiposo Blanco/patología , Animales , Aorta Torácica/efectos de los fármacos , Aorta Torácica/inmunología , Aorta Torácica/patología , Aorta Torácica/fisiopatología , Resistencia a Medicamentos/efectos de los fármacos , Endotoxemia/inmunología , Endotoxemia/metabolismo , Endotoxemia/fisiopatología , Lipopolisacáridos , Masculino , Contracción Muscular/efectos de los fármacos , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/inmunología , Músculo Liso Vascular/patología , Músculo Liso Vascular/fisiopatología , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , ARN Mensajero/metabolismo , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Choque Séptico/etiología , Choque Séptico/prevención & control , Vasoconstrictores/farmacología , Vasodilatadores/farmacologíaRESUMEN
<p><b>OBJECTIVE</b>To investigate the expression of indoleamine 2, 3-dioxygenase (IDO) in breast cancer and its correlation with clinicopathologic factors and prognosis.</p><p><b>METHODS</b>The expression of IDO, CD31, CD105 proteins in 40 specimens of breast cancer were assessed by immunohistochemistry.</p><p><b>RESULTS</b>The overexpression rate of IDO in breast cancer was 67.5% (27/40), and expression of IDO was closely associated with clinical stage and lymph nodes metastasis. The disease-free survival rate in patients with IDO overexpression was not significantly lower than that in patients with negative or low expression of IDO (P > 0.05). Moreover, the expression of IDO was positively correlated with CD105-labeled microvessel density (r = 0.659, P < 0.05).</p><p><b>CONCLUSIONS</b>Expression of IDO is associated with clinical stage and lymph nodes metastasis, and microvessel densitty. IDO expression may promote the growth and metastasis of breast cancer, probably via the increased agiogenesis. A larger sample study is needed to verify whether the prognosis of beast cancer is significantly correlated with IDO expression.</p>