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首页> 外文期刊>Nitric oxide: Biology and chemistry >Sulfur dioxide attenuates sepsis-induced cardiac dysfunction via inhibition of NLRP3 inflammasome activation in rats
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Sulfur dioxide attenuates sepsis-induced cardiac dysfunction via inhibition of NLRP3 inflammasome activation in rats

机译:二氧化硫通过抑制大鼠NLRP3炎症组活化抑制败血症诱导的心脏功能障碍

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Objective: Sulfur dioxide (SO_2) plays an important role in maintaining homeostasis of cardiovascular system. This study was aimed to investigate cardioprotective effects of SO_2 on in the rat and the underlying mechanism. Methods and results: Sepsis model induced by cecal ligation and puncture (CLP) in rats were used. SO_2 donor (NaHSO_3/Na_2SO_3, 1:3 M/M) was administered intraperitoneally at a dose of 85 mg/kg. Primary neonatal rat cardiac ventricular myocytes (NRCMs) were stimulated with LPS (1 mg/mL) in presence or absence of different concentrations of SO_2 (10, 50 and 100 μmol/L). SO_2 donor could restore the decreased levels of SO_2 in plasma and heart of septic rats. SO_2 exhibited dramatic improvement in cardiac functions. At 24 h after CLP, SO_2 treatments decreased the number of TUNEL-positive cells, Bax/Bcl-2 ratio and activity of caspase-3. Moreover CLP-induced inflammatory response was also relieved by SO_2. In NRCMs, SO_2 could suppress the LPS-induced myocardial injury, leading to an increase in cell viability, a decrease in LDH and apoptotic rate. Western blot showed that the expression of TLR4, NLRP3, and Caspase-1 were obviously increased in myocardial tissue of CLP group or in NRCMs of LPS group, while SO_2 significantly inhibited the CLP-induced or LPS-induced TLR4, NLRP3, and Caspase-1 expression. Conclusion: SO_2 attenuated sepsis-induced cardiac dysfunction likely in association with the inhibiting inflammation via TLR4/NLRP3 signaling pathway.
机译:目的:二氧化硫(SO_2)在维持心血管系统的稳态中起着重要作用。本研究旨在调查SO_2对大鼠和潜在机制的心脏保护作用。方法和结果:使用盲肠连接和穿刺(CLP)诱导的败血症模型。 SO_2供体(NaHSO_3 / NA_2SO_3,1:3m / m)以85mg / kg的剂量腹膜施用。用LPS(1mg / ml)在不同浓度的SO_2(10,50和100μmol/ L)的情况下用LPS(1mg / ml)刺激原发性新生大鼠心室肌细胞(NRCMS)。 SO_2供体可以恢复血浆和脓毒症大鼠心脏中的SO_2水平降低。 SO_2表现出心脏功能的急剧改善。在CLP之后在24小时,SO_2治疗减少了调节阳性细胞的数量,Bax / Bcl-2比和Caspase-3的活性。此外,SO_2也缓解了CLP诱导的炎症反应。在NRCMS中,SO_2可以抑制LPS诱导的心肌损伤,导致细胞活力的增加,LDH和凋亡率降低。 Western印迹表明,CLP组的心肌组织或LPS组心肌组织明显增加了TLR4,NLRP3和Caspase-1的表达,而SO_2显着抑制了CLP诱导的或LPS诱导的TLR4,NLRP3和Caspase- 1表达。结论:SO_2衰减脓毒症诱导的心脏功能障碍可能与TLR4 / NLRP3信号通路抑制炎症相关联。

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