ETHANOL AND IL6 SIGNAL TRANSDUCTION

酒精性肝病如果是酒精性肝毒性的结果 再加上肝脏再生能力受损。在动物模型中， 急性或长期接触乙醇会损害下列肝脏再生 肝部分切除或化学性肝损伤，但其机制 目前尚不清楚乙醇是如何抑制肝脏再生的。近期 在白介素6(IL-6)缺陷的“基因敲除”小鼠中获得的证据 提示IL-6对信号转导的激活和激活 转录蛋白3(STAT3)是肝脏中的关键步骤 再生。初步实验表明，急性治疗与 乙醇可阻断IL-2诱导的大鼠肝脏STAT3的激活 6体外或体内肝部分切除。这些发现表明， 乙醇的抗再生作用至少在一定程度上是由 通过阻断IL-6诱导的STAT3活化。这一机制通过它 乙醇抑制IL-6诱导的STAT3激活将通过 急性乙醇处理对IL-6诱导的影响分析 信号转导级联反应，包括IL-6与其相互作用 受体、gp130蛋白的酪氨酸磷酸化和IL-6- 诱导JAK激酶的激活。慢性乙醇对大鼠心脏功能的影响 将探索IL-6或肝部分切除术诱导的STAT3激活 在以含乙醇的液体饮食维持的大鼠中。身份识别 乙醇调节的IL信号通路不仅会增强我们的 对酒精性肝病发病机制的认识 也可能有助于阐明乙醇对其他神经细胞信号系统的影响 大脑等组织。

Alcoholic liver disease if the result of alcohol-induced hepatotoxicity coupled with impaired hepatic regenerative capacity. In animal models, acute or chronic exposure to ethanol impairs liver regeneration following partial hepatectomy or chemically induced liver injury, but the mechanisms by which ethanol inhibits liver regeneration are still unknown. Recent evidence obtained in 'knock-out' mice deficient in interleukin-6 (il-6) indicates that activation by IL-6 of the signal transducer and activation of transcription protein 3 (Stat3) is a critical step in liver regeneration. Preliminary experiments have shown that acute treatment with ethanol can block the activation of Stat3 in the rat liver, induced by IL- 6 in vitro or by partial hepatectomy in vivo. These findings suggest that the anti-regenerative effects of ethanol are mediated, at least in part, through blocking IL-6 induced Stat3 activation. The mechanism by which ethanol inhibits IL-6-induced Stat3 activation will be explored by analyzing the effects of acute ethanol treatment on the IL-6-induced signal transduction cascade, including the interaction of IL-6 with its receptor, the tyrosine phosphorylation of the gp130 protein and IL-6- induced activation of the JAK kinases. The effects of chronic ethanol on Stat3 activation induced by IL-6 or partial hepatectomy will be explored in rats maintained on a ethanol-containing liquid diet. Identification of the IL-signaling pathway modulated by ethanol will not only enhance our understanding of the pathogenesis of alcoholic-induced liver disease but may also shed light on the effects of ethanol on signal systems in other tissues such as the brain.