RESUMO
BACKGROUND: Intracellular calcium overload is a major contributing factor to diaphragmatic dysfunction triggered by sepsis. In this study, the possible role of dantrolene, a ryanodine receptor inhibitor, in preventing the release of calcium from the sarcoplasmic reticulum in diaphragmatic dysfunction and weakness was explored. METHODS: A middle-grade severity sepsis rat model was established for the effects of treatment with dantrolene, on diaphragm harvested 24 h after cecal ligation and puncture (CLP), and analyzed using functional, histologic, and biomarker assays. RESULTS: It was found that in septic rats, treatment with dantrolene significantly improved the contractility, relaxation, and fatigue index of the diaphragm in a dose-dependent manner. The benefits are associated with improvement in ultrastructural changes of Z band integrity and myofilament arrangements along with increases both in the ratio of slow-twitch type composition. Moreover, dantrolene effectively inhibits the overexpression of high-mobility group box 1 and reduces the calpain-1-caspase-3 proteolytic activity. CONCLUSIONS: Dantrolene can effectively attenuate the dysfunction of diaphragm in septic rats; Furthermore, the beneficial effects were associated with downregulation of high-mobility group box 1 and calpain-1-caspase-3 proteolytic activity.
Assuntos
Dantroleno/farmacologia , Diafragma/efeitos dos fármacos , Proteína HMGB1/metabolismo , Relaxantes Musculares Centrais/farmacologia , Proteólise/efeitos dos fármacos , Sepse/tratamento farmacológico , Animais , Biomarcadores/metabolismo , Calpaína/metabolismo , Caspase 3/metabolismo , Dantroleno/uso terapêutico , Diafragma/metabolismo , Diafragma/fisiopatologia , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Masculino , Relaxantes Musculares Centrais/uso terapêutico , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Sepse/metabolismo , Sepse/fisiopatologiaRESUMO
Dendritic cells (DCs) are specialized antigen-presenting cells. Immature dendritic cells can be activated into mature dendritic cells by recognizing antigens, then the antigens are processed and pres-ented to T lymphocytes. DCs play a vital role in initiating immune response, regulating immune response and maintaining immune tolerance. Therefore, regulating the immune function of DCs can be used to treat diseases such as autoimmune diseases and tumors. With the deepening of research on the regulation of DCs, people have gradually realized that the existence of reactive oxygen species (ROS) in DCs is of great significance. ROS is a term of strong oxidizing reactive species, and the dynamic balance of its pro-duction and removal is the key to maintaining cell redox homeostasis. ROS of physiological level is an im-portant molecule involved in a variety of signal pathways, which can regulate cell growth, differentiation and different physiological and biochemical reactions. The changes in the level of ROS affect the state and function of cells. In addition, because there are many ways to produce ROS in the cell, the effects of dif-ferent sources of ROS on DCs are not usually the same; and even the same source of ROS may have dif-ferent effects when cells are in different states. This article summarized the influence of intracellular ROS changes and different sources of ROS on the differentiation, maturation and function of DCs, aiming to re-veal how ROS plays an important role in regulating the immune function of DCs. At the same time, this article also showed the urgent need for the in-depth study of ROS regulating the function of DCs, which may help the application of DCs immune regulation to a wider range of disease treatments.
RESUMO
The aim of the current study was to investigate the effect of chronic dexamethasone (Dex) administration on rat diaphragm function and sensitivity to rocuronium and musclefiber transformation. Adult male SpragueDawley rats were randomized to receive a daily intraperitoneal injection of Dex to evaluate whether alterations in diaphragm function and susceptibility to rocuronium would be induced. In addition, diaphragm contractile properties, histopathology and isometric twitch tensions of nervehemidiaphragm preparations were evaluated. Dex administration led to impaired diaphragm force generation, increased fatigue resistance and a prolonged halfrelaxation time, as well as timetopeak tension. Dex treatment led to desensitization of the rat diaphragm to rocuronium, as demonstrated by a shift of the rocuronium concentrationtwitch tension curves to the right. Histochemical analysis of adenosine triphosphatase revealed that the distribution and crosssectional area of type II fibers were decreased in rats exposed to Dex. The present study indicates that chronic Dex treatment induced alterations in muscle function and that susceptibility to rocuronium is associated with muscle fibertype transformation, which may aid in directing future administration of muscle relaxants.