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首页> 外文期刊>Cytokine >Blockade of multiple but not single cytokines abrogates downregulation of angiotensin II type-I receptors and anticipates septic shock.
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Blockade of multiple but not single cytokines abrogates downregulation of angiotensin II type-I receptors and anticipates septic shock.

机译:多种而不是单种细胞因子的阻断消除了血管紧张素II型I受体的下调,并有望引起败血性休克。

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In this prospective, randomized animal study, the role of proinflammatory cytokines in the pathogenesis sepsis-induced circulatory failure with downregulation of angiotensin-II-type-I-(AT(1))-receptors was investigated. Sepsis in wild-type mice and in mice with deficiencies for TNF-alpha, IL-1beta, IFN-gamma or IL-6 was induced by cecal ligation and puncture (CLP) and wild-type mice were injected with cytokines. Animals were treated with glucocorticoids or small interfering RNA (siRNA) targeting single or multiple cytokines or NF-kappaB. Vascular smooth muscle cells (VSMCs) were incubated with cytokines. CLP resulted in circulatory failure and a significant downregulation of AT(1)-receptors. Injection of single proinflammatory cytokines also strongly downregulated AT(1)-receptors paralleled by a markedly endogenous liberation of further cytokines, whereas, simultaneous blockade of these endogenously activated cytokines by dexamethasone prevented downregulation of AT(1)-receptors. Furthermore, inhibition of multiple but not single cytokines by treatment with siRNA against multiple cytokines or NF-kappaB significantly attenuated CLP-induced AT(1)-receptor downregulation and prevented septic circulatory failure. Our data demonstrate that downregulation of AT(1)-receptors during sepsis is due to multiple but not single cytokines and define a relevant role for NF-kappaB in the pathogenesis of septic shock.
机译:在这项前瞻性随机动物研究中,研究了促炎细胞因子在脓毒症诱发的循环衰竭中的作用,并下调了血管紧张素II型I-(AT(1))受体。通过盲肠结扎和穿刺(CLP)诱导野生型小鼠和TNF-α,IL-1beta,IFN-γ或IL-6缺乏的小鼠败血症,并向野生型小鼠注射细胞因子。用糖皮质激素或靶向单种或多种细胞因子或NF-κB的小干扰RNA(siRNA)治疗动物。将血管平滑肌细胞(VSMC)与细胞因子一起孵育。 CLP导致循环衰竭和AT(1)受体的显着下调。注射单个促炎细胞因子也会强烈下调AT(1)受体,同时显着内源性释放其他细胞因子,而地塞米松同时阻断这些内源性激活细胞因子可防止AT(1)受体下调。此外,通过对多种细胞因子或NF-κB的siRNA抑制多种而不是单一细胞因子,可显着减弱CLP诱导的AT(1)-受体下调并防止败血性循环衰竭。我们的数据表明败血症期间AT(1)受体的下调是由于多种而非单一的细胞因子引起的,并定义了NF-κB在败血性休克发病中的相关作用。

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