Nitric Oxide Production and its Contribution to Hepatocyte Proliferation in Normal Juvenile Rats
Nitric Oxide Production and its Contribution to Hepatocyte Proliferation in Normal Juvenile Rats
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DOI：
10.1292/jvms.09-0551
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发表时间：
2010-07-01
影响因子：
1.2
通讯作者：
Takizawa, Tatsuya
中科院分区：
文献类型：
--
作者：
Inukai, Naoto;Uchida, Mayuko;Takizawa, Tatsuya
据报道，一氧化氮（NO）是肝脏再生过程中增强肝细胞增殖的关键介质。幼年肝细胞在未分化状态下具有很强的增殖能力，但NO产生的机制及其对肝细胞增殖的贡献尚不完全清楚。本研究旨在研究正常肝脏中 NO 的产生及其对幼年大鼠肝细胞增殖的贡献。使用自旋捕获器，然后使用 Fe-N,N-二乙基二硫代氨基甲酸酯复合物作为大鼠肝脏中的 NO 捕获试剂，通过电子顺磁共振波谱法定量评估内源性 NO 的产生。肝脏中NO的产生在出生后3周显着达到峰值，但一氧化氮合酶（NOS）3的表达在出生后2至5周内没有变化，而NOS 1和NOS 2 mRNA未检测到。通过将 5-溴-2'-脱氧尿苷掺入 DNA 来测量，发现当使用 NOS 抑制剂 N-G-硝基-L-精氨酸甲酯抑制内源性 NO 产生时，肝细胞增殖显着下降。这些发现表明，内源性 NO 产生在出生后 3 周达到峰值，当 NO 产生受到抑制时，肝细胞增殖显着下降。因此，这项研究为研究 NO 对幼年肝脏生长和肝脏成熟的贡献提供了新的见解。
Nitric oxide (NO) has been reported as a key mediator in enhancing hepatocyte proliferation during liver regeneration. Juvenile hepatocytes have a strong ability to proliferate while still in their undifferentiated state but the mechanism of NO production and its contribution to hepatocyte proliferation are not yet fully understood. The present study was designed to investigate NO production in the normal liver and its contribution to hepatocyte proliferation in juvenile rats. Endogenous NO production was evaluated quantitatively using a spin trap followed by electron paramagnetic resonance spectroscopy with the Fe-N, N-diethyldithiocarbamate complex as an NO-trapping reagent in the rat liver. NO production in the liver significantly peaked at 3 weeks after birth, but NO synthase (NOS) 3 expression did not change between 2 to 5 weeks after birth, while NOS 1 and NOS 2 mRNA were not detected. Hepatocyte proliferation, measured by the incorporation of 5-bromo-2'-deoxyuridine into the DNA, was found to decline significantly when endogenous NO production was inhibited by the administration of the NOS inhibitor N-G-nitro-L-arginine methyl ester. These findings indicate that endogenous NO production peaked at 3 weeks after birth and hepatocyte proliferation declined significantly when NO production was inhibited. Thus, this study provides a novel insight into the contribution of NO to hepatic growth and liver maturation in juveniles.