RESUMO
Severe acute pancreatitis (SAP) accounts for up to 20% of acute pancreatitis (AP) cases. The absence of effective treatment options has resulted in a high rate of morbidity and mortality. Emodin is a major component of the Chinese herb rhubarb, which has been widely used in the treatment of numerous diseases, including inflammation and cancer. There are a limited number of studies however, that have investigated the effectiveness of emodin in the treatment of SAP. The present study used a rat model of SAP, to investigate the effect and molecular mechanisms of emodin treatment. Administration of emodin was identified to significantly attenuate SAP, as determined by serum amylase analysis and histological assessment of edema, vacuolization, inflammation and necrosis (P<0.01). Furthermore, treatment with emodin markedly inhibited nuclear factor (NF)κB DNAbinding activity (P<0.01) and the serum expression levels of tumor necrosis factorα, interleukin (IL)6 and IL1ß (P<0.05). This attenuation was associated with decreased malondialdehyde and increased superoxide dismutase levels in the pancreatic tissues and serum (P<0.05). This study indicated that administration of exogenous emodin had therapeutic effects on the severity of SAP. The mechanism may be due to inhibition of NFκB activation resulting in an antioxidation response, which can subsequently suppress the expression of cytokines.
Assuntos
Antioxidantes/farmacologia , Emodina/farmacologia , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Pancreatite/patologia , Doença Aguda , Amilases/sangue , Animais , Antioxidantes/uso terapêutico , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Emodina/uso terapêutico , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Estimativa de Kaplan-Meier , Masculino , Malondialdeído/análise , Malondialdeído/sangue , NF-kappa B/antagonistas & inibidores , Pancreatite/tratamento farmacológico , Pancreatite/mortalidade , Ratos , Ratos Sprague-Dawley , Rheum/química , Rheum/metabolismo , Índice de Gravidade de Doença , Superóxido Dismutase/análise , Superóxido Dismutase/sangue , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Pancreatic cancer (PC) is the fourth leading cause of cancer-related mortality in the United States. There is no effective serum biomarker for the early diagnosis of PC at present. Although serum UL16-binding protein 2 (ULBP2) and macrophage inhibitory cytokine-1 (MIC-1) levels are reported to be elevated in PC patients, the diagnostic and prognostic value of ULBP2 and MIC-1 alone or in combination remains unknown. The aim of the present case-control study was to compare the diagnostic value of ULBP2, MIC-1 and carbohydrate antigen 19-9 (CA19-9) in 359 serum samples, consisting of 152 cases of PC, 20 cases of pre-pancreatic cancer, 91 cases of chronic pancreatitis (CP) and 96 normal controls (NC). All patients were followed up for a median of 2 years. It was found that the serum levels of ULBP2, MIC-1 and CA19-9 were significantly higher in the PC patients compared with those in the NC group. In distinguishing PC from the CP, the highest sensitivity and specificity were ULBP2 (0.878) and CA19-9 (0.816), respectively. The area under the receiver operating characteristic curve of ULBP2 was 0.923, which was the highest of the three biomarkers. MIC-1 was the optimal choice for the diagnosis of early-stage PC (area under the curve, 0.831). Overall, MIC-1 in combination with ULBP2 improved the diagnostic accuracy in differentiating PC from CP and NC. In addition, a higher level of MIC-1 was correlated with a poorer prognosis, as calculated by the Kaplan-Meier test (P=0.039). Patients with serum MIC-1 levels of ≥1,932 ng/ml had a median survival time of 15.62±2.44 months (mean ± standard deviation) vs. 18.66±2.43 months in patients with a lower level of MIC-1. Overall, combined detection of serum MIC-1 and ULBP2 improved the diagnostic accuracy in differentiating PC from CP and NC, and serum MIC-1 level alone was a predictor of survival in the patients with PC.
RESUMO
A 62-year-old woman was admitted to our hospital in 2011 because of recurrent abdominal pain, nausea and constipation for six months. Computed tomography enterography (CTE) showed tortuous thread-like calcifications in the ileocolic vein and right colic vein, while colonoscopy revealed purple-blue mucosa extending from the cecum to the splenic flexure. Based on the results of these tests, the patient was diagnosed with idiopathic mesenteric phlebosclerosis (IMP). She had a history of Chinese medical liquor intake for one and a half years and her symptoms subsided after conservative treatment. In 2013, a 63-year-old male patient who presented with recurrent lower right abdominal pain, bloating, melena and diarrhea for fifteen months was admitted to our institution. Colonoscopy and CTE led to the diagnosis of IMP. He also used Chinese medical liquor for approximately 12 years. The patient underwent total colectomy and the postoperative course was uneventful. We searched for previously published reports on similar cases and analyzed the clinical data of 50 cases identified in PubMed. As some of these patients admitted use of Chinese medicines, we hypothesize that Chinese medicines may play a role in the pathogenesis of IMP.
Assuntos
Medicamentos de Ervas Chinesas/efeitos adversos , Mesentério/irrigação sanguínea , Calcificação Vascular/induzido quimicamente , Colonoscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Flebografia/métodos , Valor Preditivo dos Testes , Fatores de Risco , Esclerose , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Calcificação Vascular/diagnóstico , Calcificação Vascular/terapia , Veias/efeitos dos fármacos , Veias/patologiaRESUMO
Based on the function of chemokine fractalkine (FKN), acting as both adhesion and chemoattractant, FKN plays a role in acute inflammatory response. In this study, we investigated the mechanism of FKN mediated upregulation inflammation in severe acute pancreatitis (SAP) rat models. Western blot, reverse transcriptase-polymerase chain reaction, and immunofluorescence demonstrated that FKN and its receptor CX3CR1 were overexpressed in cerulein-stimulated AR42J cells. AG490 and FKN-siRNA inhibited activation of Janus kinase/signal transducers and activators of transcription (Jak/Stat) in cerulein-stimulated AR42J cells. Following exposure AG490 and FKN-siRNA inhibited tumor necrosis factor-alpha expression by enzyme-linked immunosorbent assay and immunohistochemistry in vivo the SAP rat models. These results showed FKN and CX3CR1 were involved inflammatory response in cerulein-stimulated AR42J cells. FKN upregulates inflammation through CX3CR1 and the Jak/Stat pathway in SAP rat models.