RESUMEN
Although enteric glial cells (EGCs) have been demonstrated to play a key role in maintaining intestinal epithelial barrier integrity, it is not known how EGCs regulate this integrity. We therefore hypothesized that glial-derived neurotrophic factor (GDNF) produced by EGCs might be involved in this regulation. Here we investigated the role of GDNF in regulating epithelial barrier function in vivo. Recombinant adenoviral vectors encoding GDNF (Ad-GDNF) were administered intracolonically in experimental colitis induced by dextran sulphate sodium (DSS). The disease activity index (DAI) and histological score were measured. Epithelial permeability was assayed using Evans blue dye. The anti-apoptotic potency of GDNF in vivo was evaluated. The expression of tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and myeloperoxidase (MPO) activity were measured by ELISA assay and/or RT-PCR. The expression of ZO-1, Akt, caspase-3, and NF-kappaB p65 was analysed by western blot assay. Our results showed that GDNF resulted in a significant reduction in enhanced permeability, inhibited MPO activity, IL-1beta and TNF-alpha expression, and increased ZO-1 and Akt expression. Moreover, GDNF strongly prevented apoptosis in vivo and significantly ameliorated experimental colitis. Our findings indicate that GDNF participates directly in restoring epithelial barrier function in vivo via reduction of increased epithelial permeability and inhibition of mucosal inflammatory response, and is efficacious in DSS-induced colitis. These findings support the notion that EGCs are able to regulate intestinal epithelial barrier integrity indirectly via their release of GDNF in vivo. GDNF is namely an important mediator of the cross-talk between EGCs and mucosal epithelial cells. GDNF may be a useful therapeutic approach to the treatment of inflammatory bowel disease.
Asunto(s)
Colitis/terapia , Factor Neurotrófico Derivado de la Línea Celular Glial/fisiología , Absorción Intestinal/fisiología , Adenoviridae/genética , Animales , Apoptosis , Colitis/patología , Colitis/fisiopatología , Colon/metabolismo , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos/métodos , Femenino , Terapia Genética/métodos , Vectores Genéticos , Factor Neurotrófico Derivado de la Línea Celular Glial/genética , Factor Neurotrófico Derivado de la Línea Celular Glial/metabolismo , Mediadores de Inflamación/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/fisiopatología , Proteínas de la Membrana/metabolismo , Ratones , Ratones Endogámicos BALB C , FN-kappa B/metabolismo , Permeabilidad , Peroxidasa/metabolismo , Fosfatidilinositol 3-Quinasas/fisiología , Fosfoproteínas/metabolismo , Transducción de Señal/fisiología , Proteína de la Zonula Occludens-1RESUMEN
BACKGROUND: Resistin level is high in patients with severe acute pancreatitis (SAP), and resistin is expected to be a new marker for evaluating the severity of acute pancreatitis. OBJECTIVE: To explore the influence of integrated traditional Chinese and Western medicine therapy on serum resistin levels in SAP patients. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: Twenty-eight SAP patients meeting inclusion criteria from Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University were included, and the patients were randomly divided into treatment group and placebo group. There were 13 patients in the treatment group and 15 patients in the placebo group. Patients in the treatment group were given traditional Chinese herbal medicine in addition to the conventional treatment. Patients in the placebo group were given placebo in addition to the conventional treatment. MAIN OUTCOME MEASURES: The serum resistin levels on admission, and days 1, 3, 5, and 7 after the admission were detected. RESULTS: The serum resistin levels on admission in all the patients were higher than normal level, and there was no significant difference between the two groups (P>0.05). On days 1, 3, 5, and 7 after admission, the resistin levels in the treatment group were (3.29 + or - 1.66) microg/L, (3.71 + or - 1.05) microg/L, (3.08 + or - 1.47) microg/L and (3.62 + or - 1.67) microg/L, and in the control group (5.16 + or - 1.93) microg/L, (5.07 + or - 1.53) microg/L, (4.88 + or - 1.47) microg/L and (5.12 + or - 1.48) microg/L, respectively. The resistin levels were lower in the treatment group than in the control group (P<0.05). CONCLUSION: Serum resistin level in SAP patients can be decreased by integrated traditional Chinese medicine and Western medicine therapy.
Asunto(s)
Medicina Tradicional China , Pancreatitis/sangre , Pancreatitis/tratamiento farmacológico , Resistina/sangre , Biomarcadores , Medicamentos Herbarios Chinos/uso terapéutico , Humanos , Resultado del TratamientoRESUMEN
OBJECTIVE: To study the risk factors for severe acute pancreatitis (SAP) complicated by pancreatic encephalopathy (PE). METHODS: Clinical data from 255 patients with SAP from January 2005 to December 2006 were reviewed. Thirty-one SAP patients had PE, and 224 SAP patients did not. Clinical characteristics of SAP patients in both PE group and non-PE group were analyzed. RESULTS: Ranson scale and the incidence rates of acute respiratory distress syndrome (ARDS), renal failure, hypoproteinemia, hypocalcemia and hyperglycosemia in PE group were higher than those in non-PE group (P<0.05). There were no significant differences in acute physiology and chronic health evaluation II and CT severity index scales, the activities of amylase and lipase, the incidence rate of liver function failure, the infection rate and the operability between the PE group and the non-PE group (P>0.05). Multivariate logistic regression analysis showed that ARDS and hyperglycosemia were high risk factors. Cure rate in PE group was higher than that in non-PE group. CONCLUSION: Nosogenesis of PE is the result of multiple factors. ARDS and hyperglycosemia may be the high risk factors for PE.
Asunto(s)
Encefalopatías/etiología , Hiperglucemia/etiología , Pancreatitis Aguda Necrotizante/complicaciones , Síndrome de Dificultad Respiratoria/etiología , Adulto , China/epidemiología , Femenino , Humanos , Hiperglucemia/epidemiología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Síndrome de Dificultad Respiratoria/epidemiología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
OBJECTIVE: To explore the mechanism of Chaiqin Chengqi Decoction (CQCQD) in treatment of rats with acute necrotizing pancreatitis (ANP). METHODS: Thirty SD rats were randomly divided into 3 groups: sham-operated (SO) group, ANP group and CQCQD-treated group. ANP was induced by retro-pumping 3.5% sodium cholate to common bile duct. Blood sample was collected from abdominal vein for examination and the pancreatic tissue samples were taken for making pathology section 6 hours later. The pancreatic tissue (HE staining) was observed by light microscope. The content of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) was detected with the method of enzyme-linked immunosorbent assay, and the activation of nuclear factor-kappaB (NF-kappaB) in pancreas was detected by immunohistochemical method. RESULTS: Compared with the SO group, there was dramatic increase in the white blood cell (WBC) counts and AMY level in the ANP group (P<0.05, P<0.01). Compared with the ANP group, the WBC counts and AMY level in CQCQD-treated group were significantly reduced (P<0.05). The edema, inflammatory infiltration, haemorrhage and necrosis scores and total pathological score in the ANP group were obviously higher than those in the SO group (P<0.01). The edema, haemorrhage and inflammatory infiltration scores and the total pathological score in CQCQD-treated group were decreased (P<0.05). The integral optical density of NF-kappaB p65 positive cells of pancreas in CQCQD-treated group was lower than that in the ANP group (P<0.05). CONCLUSION: CQCQD can reduce the content of serum TNF-alpha and IL-6, depress the activation of NF-kappaB, and lessen the pancreatic lesions.