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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Evidence of nitric oxide, a flow-dependent factor, being a trigger of liver regeneration in rats.
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Evidence of nitric oxide, a flow-dependent factor, being a trigger of liver regeneration in rats.

机译:一氧化氮(一种与流量有关的因子)是大鼠肝脏再生的证据。

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The hypothesis tested was that the hemodynamic consequence of partial hepatectomy (PHX) triggers the cascade of events that leads to liver regeneration. After PHX, all the portal flow must go through the remaining vascular bed, thus producing increased shear stress and release of nitric oxide (NO), which then initiates the next stages of the regeneration process. As an index of triggering of the regeneration cascade, we used an in vitro bioassay detecting the appearance of proliferating factors (PFs; various growth factors, cytokines, and hormones) in plasma 4 h after two-thirds PHX in rats. PF levels, assessed using proliferation of cultured hepatocytes, were elevated in two-thirds PHX rats, fully blocked by the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME), and restored by L-arginine. L-NAME inhibited liver weight restoration at 48 h but resulted in high mortality. L-NAME lacked toxic effects in non-PHX rats. NO was directly antiproliferative on cultured cells, suggesting that the proliferative effect of NO in vivo was secondary to the activation of other proliferative stimuli. The data support the hypothesis that vascular shear stress induced release of NO following PHX serves as a primary trigger to initiate the regeneration process.
机译:测试的假设是部分肝切除术(PHX)的血液动力学后果触发了导致肝脏再生的一系列事件。 PHX后,所有门脉血流都必须经过其余的血管床,从而产生增加的剪切应力并释放一氧化氮(NO),然后启动再生过程的下一个阶段。作为触发再生级联的指标,我们使用体外生物测定法检测三分之二的PHX后4 h大鼠血浆中增殖因子(PF;各种生长因子,细胞因子和激素)的出现。使用培养的肝细胞增殖评估的PF水平在三分之二的PHX大鼠中升高,被NO合酶抑制剂N(G)-硝基-L-精氨酸甲酯(L-NAME)完全阻断,并由L-精氨酸恢复。 L-NAME在48 h抑制肝脏重量的恢复,但导致高死亡率。 L-NAME在非PHX大鼠中没有毒性作用。 NO对培养的细胞具有直接的抗增殖作用,提示NO在体内的增殖作用仅次于其他增殖刺激的激活。数据支持以下假设:在PHX之后,血管切应力诱导的NO释放是引发再生过程的主要触发因素。

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