RESUMEN
Hepatic ischemia/reperfusion injury (IRI) is an adverse effect for liver transplantation which is characterized by immune response mediated inflammation. Recent studies report that neutrophil extracellular traps (NETs) are implicated in hepatic IRI. The aim of this study was to explore the mechanism of action of tetramethylpyrazine (TMP), the main chemical composition of Ligusticum chuanxiong in treatment of ischemic related diseases. Data showed that hepatic IRI increases the leak of alanine aminotransferase (ALT) and aspartate transaminase (AST), and stimulates formation of NETs. Extracellular DNA/NETs assay, hematoxylin-eosin (HE) staining, immunofluorescence assay, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) and Western blot assay, showed that TMP significantly reduces formation of NETs and alleviates hepatic IRI. Moreover, TMP and Diphenyleneiodonium (DPI) suppressed ROS production in neutrophils. In addition, analysis showed that activation of NADPH oxidase plays a role in formation of NETs triggered by hepatic IRI. Notably, TMP inhibited formation of NETs though inhibition of NADPH oxidase. Additionally, Combination treatment using TMP and DPI was more effective compared with monotherapy of either of the two drugs. These findings show that combination therapy using TMP and DPI is a promising method for treatment hepatic IRI.
Asunto(s)
Antioxidantes/farmacología , Trampas Extracelulares/efectos de los fármacos , Trasplante de Hígado/rehabilitación , Compuestos Onio/farmacología , Pirazinas/farmacología , Daño por Reperfusión/tratamiento farmacológico , Alanina Transaminasa/metabolismo , Animales , Aspartato Aminotransferasas/metabolismo , Ácidos Nucleicos Libres de Células/antagonistas & inhibidores , Ácidos Nucleicos Libres de Células/sangre , Modelos Animales de Enfermedad , Sinergismo Farmacológico , Quimioterapia Combinada/métodos , Trampas Extracelulares/metabolismo , Etiquetado Corte-Fin in Situ , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/cirugía , Trasplante de Hígado/métodos , Masculino , NADPH Oxidasas/antagonistas & inhibidores , NADPH Oxidasas/metabolismo , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismo , Neutrófilos/patología , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Daño por Reperfusión/cirugía , Resultado del TratamientoRESUMEN
Gastric cancer (GC) is one of the most common malignancies in the world. Exosomes, a subset of extracellular vesicles with an average diameter of 100 nm, contain and transfer a variety of functional macromolecules such as proteins, lipids, and nucleic acids. A large number of studies indicated that exosomes can play a significant role in the initiation and development of GC via facilitating intercellular communication between gastric cancer cells and microenvironment. Exosomal RNAs, one of the key functional cargos, are involved in the pathogenesis, development, and metastasis of GC. In addition, recent studies elucidated that exosomal RNAs may serve as diagnostic and prognostic biomarkers or therapeutic targets for GC. In this review, we summarized the function of exosomal RNA in the tumorigenesis, progression, diagnosis, and treatment of GC, which may further unveil the functions of exosome and promote the potentially diagnostic and therapeutic application of exosomes in GC.
