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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Protective effect of c5 shRNA on myocardial ischemia-reperfusion injury in rats
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Protective effect of c5 shRNA on myocardial ischemia-reperfusion injury in rats

机译:c5 shRNA对大鼠心肌缺血再灌注损伤的保护作用

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摘要

Myocardial ischemia and reperfusion (MI/R) injury is associated with activation of the complement system. Complement activation generates a series of bioactive substances, including early (C3a, C3b) and terminal (C5a, C5b-9) components. The terminal complement components are key mediators of MI/R injury. This study investigated whether C5 shRNA preconditioning has protective effects following MI/R injury and its potential mechanism. Rats were injected with C5 shRNA 2 days before induction of ischemia. The effects of C5 shRNA were evaluated by the assessment of heart function, infarct size, histopathology, inflammatory cytokine levels, and the plasma level of troponin T. Akt phosphorylation was assessed by immunoblotting. C5 shRNA efficiently inhibited C5 expression both in vitro and in vivo, and attenuated MI/R injury. C5 shRNA preconditioning significantly decreased the level of troponin T and the production of pro-inflammatory cytokine. The infarct size was decreased by 40% in C5 shRNA treated rats. Akt phosphorylation increased after C5 shRNA preconditioning. These results suggest that C5 shRNA preconditioning in rats has protective effects following MI/R injury; this may be partly effected by mediating the activation of the PI3K pathway and by phosphorylation of Akt.
机译:心肌缺血和再灌注(MI / R)损伤与补体系统的激活有关。补体激活产生一系列生物活性物质,包括早期(C3a,C3b)和末端(C5a,C5b-9)组分。末端补体成分是MI / R损伤的关键介质。这项研究调查了C5 shRNA预处理在MI / R损伤后是否具有保护作用及其潜在机制。在诱导缺血前2天,给大鼠注射C5 shRNA。通过评估心脏功能,梗死面积,组织病理学,炎性细胞因子水平和血浆肌钙蛋白T水平来评估C5 shRNA的作用。通过免疫印迹评估Akt磷酸化。 C5 shRNA在体外和体内均可有效抑制C5表达,并减轻MI / R损伤。 C5 shRNA预处理可显着降低肌钙蛋白T水平和促炎性细胞因子的产生。在C5 shRNA处理的大鼠中,梗塞面积减少了40%。 C5 shRNA预处理后,Akt磷酸化增加。这些结果表明,C5 shRNA预处理在MI / R损伤后具有保护作用。这可能部分是通过介导PI3K途径的激活和Akt的磷酸化来实现的。

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