RESUMEN
BACKGROUND/AIMS: Severe acute pancreatitis (SAP) is a sudden inflammation of the pancreas. The traditional Chinese medicine formula Dachengqi decoction (DCQD) is proven to be beneficial in the comprehensive treatment for pancreatitis patients in clinical practice. However, the molecular mechanism of DCQD on SAP remains unclear. High mobility group box 1(HMGB1) that functions as a damage-associated molecular pattern molecule (DAMP) has attracted much interest. METHODS: In this study, we used lipopolysaccharide (LPS) and cerulein to induce severe acute pancreatitis in C57BL/6 mice with subsequent administration with low, medium and high dose (2.3 g/kg, 7 g/kg and 21 g/kg, respectively) of DCQD. RESULTS: DCQD treatment improved the pathological score and decreased serum amylase and lipase in a dose-dependent manner. In addition, it suppressed the immune cell-induced secretion of HMGB1 and its translocation from the nucleus to the cytoplasm, thus repressing the expression of IL-6 and TNF-α. Further, pretreatment with DCQD decreased responses of TLRs, and suppressed the activation of NF-κB and p38 MAPK pathway. CONCLUSION: Decreasing the secretion of HMGB1 could reduce pro-inflammatory cytokines, which may help cutting down the risks of development from localized pathological changes to a systemic inflammatory response syndrome and even lead to multiple organ failure.
Asunto(s)
Proteína HMGB1/metabolismo , FN-kappa B/metabolismo , Extractos Vegetales/farmacología , Transducción de Señal/efectos de los fármacos , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Enfermedad Aguda , Amilasas/sangre , Animales , Ensayo de Inmunoadsorción Enzimática , Interleucina-6/sangre , Lipasa/sangre , Masculino , Ratones , Ratones Endogámicos C57BL , Microscopía Fluorescente , Páncreas/metabolismo , Páncreas/patología , Pancreatitis/metabolismo , Pancreatitis/patología , Receptor Toll-Like 4/metabolismo , Receptor Toll-Like 9/metabolismo , Factor de Necrosis Tumoral alfa/sangreRESUMEN
Proliferation and migration of vascular smooth muscle cells (VSMC) are common pathological features of diabetic vascular complications,such as atherosclerosis and hypertension. Phenotypic modulation of VSMC is the basis for VSMC proliferation and migration. Therefore, studies on VSMC phenotypic modulation and its mechanisms in diabetes mellitus were of important significance to the prevention and therapy of diabetic vascular complications. This paper introduces VSMC phenotypic modulation and the underlying mechanisms in diabetes mellitus, and summarizes advance of studies on traditional Chinese medicine intervention upon VSMC phenotypic modulation, so as to provide reference for preventing and treating diabetic vascular complications with traditional Chinese medicines.
