首页> 外文期刊>American Journal of Physiology >Intrahepatic STAT-3 activation and acute phase gene expression predict outcome after CLP sepsis in the rat.
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Intrahepatic STAT-3 activation and acute phase gene expression predict outcome after CLP sepsis in the rat.

机译:肝内STAT-3激活和急性期基因表达预测大鼠CLP败血症后的结局。

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摘要

Interleukin-6 (IL-6) regulates hepatic acute phase responses by activating the transcription factor signal transducer and activator of transcription (STAT)-3. IL-6 also may modulate septic pathophysiology. We hypothesize that 1) STAT-3 activation and transcription of alpha2-macroglobulin (A2M) correlate with recovery from sepsis and 2) STAT-3 activation and A2M transcription reflect intrahepatic and not serum IL-6. Nonlethal sepsis was induced in rats by single puncture cecal ligation and puncture (CLP) and lethal sepsis via double-puncture CLP. STAT-3 activation and A2M transcription were detected at 3-72 h and intrahepatic IL-6 at 24-72 h following single-puncture CLP. All were detected only at 3-16 h following double-puncture CLP and at lower levels than following single-puncture CLP. Loss of serum and intrahepatic IL-6 activity after double-puncture CLP correlated with mortality. Neither intrahepatic nor serum IL-6 levels correlated with intrahepatic IL-6 activity. STAT-3 activation following single-puncture CLP inversely correlated with altered transcription of gluconeogenic, ketogenic, and ureagenic genes. IL-6 may have both beneficial and detrimental effects in sepsis. Fulminant sepsis may decrease the ability of hepatocytes to respond to IL-6.
机译:白介素-6(IL-6)通过激活转录因子信号转导子和转录激活子(STAT)-3来调节肝急性期反应。 IL-6也可能调节败血性病理生理。我们假设1)STAT-3激活和alpha2-巨球蛋白(A2M)的转录与败血症的恢复相关; 2)STAT-3激活和A2M转录反映的是肝内而非血清IL-6。单孔盲肠结扎穿刺(CLP)诱导大鼠非致死性败血症,双孔CLP致死性败血症。单次穿刺CLP后3-72小时检测到STAT-3激活和A2M转录,24-72小时检测到肝内IL-6。仅在两次穿刺CLP后3-16小时检测到所有这些,并且其水平低于单次穿刺CLP后。两次穿刺CLP后血清和肝内IL-6活性的丧失与死亡率相关。肝内和血清IL-6水平均与肝内IL-6活性无关。单刺CLP后的STAT-3激活与糖异生,生酮和尿原基因的转录改变呈负相关。 IL-6在败血症中可能同时具有有益作用和有害作用。暴发性脓毒症可能会降低肝细胞对IL-6的反应能力。

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