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CROSS TALK BETWEEN BIOLOGICAL TRIPLET SYSTEMS (NEURO-ENDCRINE-IMMUNE) DURING LIVER REGENERATION

肝脏再生过程中生物三联体系统（神经内分泌免疫）之间的交互作用

基本信息

批准号：
07407030
负责人：
KASAI Shinichi
金额：
$ 14.53万
依托单位：
ASAHlKAWA MEDICAL COLLEGE
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1997
项目状态：
已结题

项目摘要

1) We suggest that the dual innervation of the liver and pancreas by single parasympathetic neurons in the vagal out put and input central nervous systems (CNS), might play a crucial role during liver regeneration. The spontaneous developed insulin-dependent diabetic rat is almost devoid of these dual innervation. After 70% hepatectomy in the diabetic rats, the liver regeneration was suppressed compared to the normal rats.2) Central neuropeptides play a role as physiological regulators in the autonomic nervous system. One of these neuropeptides, Thyrotropine-releasing hormone (TRH), is distributed the central nervous system and acts as a neurotransmitter to regulate liver functions through the vagus nerve. However, the effect of TRH on the liver regeneration is unknown. Therfore, the CNS's effect of TRH on hepatic DNA synthesis was studied in rats. Our results indicate that TRH acts in the CNS to stimulate hepatic DNA synthesis through vagal and cholinergic mechanisms, and that TRH may be the chemical messenger involved in brain regulation of hepatic proliferation.3) Central administration of neuropeptide Y (NPY) enbances bile secretion through vagal pathways in animal models. NPY nerve fibers and receptors are localized in the dorsal vagal complex (DVC), and retrograde tracing techniques have shown that hepatic vagal nerves are projected mainly from the left DVC.NPY acts in the left DVC to stimulate bile acid-independent and bicarbonate-dependent bile secretion through the left cervical and hepatic nerves ; these findings suggest that neuropeptides may act in the specific brain nuclei to regulate hepatic function.

1)我们认为迷走神经输出和输入中枢神经系统(CNS)中单个副交感神经元对肝脏和胰腺的双重神经支配在肝脏再生过程中可能起重要作用。自然发育的胰岛素依赖型糖尿病大鼠几乎不存在这些双重神经支配。糖尿病大鼠肝切除70%后，与正常大鼠相比，肝再生受到抑制。2)中枢神经肽在自主神经系统中起着生理调节作用。其中一种神经肽，促甲状腺激素释放激素(TRH)，分布在中枢神经系统，通过迷走神经作为神经递质调节肝功能。然而，TRH对肝脏再生的影响尚不清楚。因此，我们研究了TRH对大鼠肝脏DNA合成的影响。我们的结果表明，TRH通过迷走神经和胆碱能机制在中枢神经系统刺激肝脏DNA合成，TRH可能是参与脑调节肝脏增殖的化学信使。3)在动物模型中，中枢应用神经肽Y(NPY)可通过迷走神经通路促进胆汁分泌。NPY神经纤维和受体定位于迷走神经背侧复合体(DVC)，逆行追踪技术表明，肝脏迷走神经主要从左侧DVC投射。NPY作用于左侧DVC，通过左侧颈神经和肝神经刺激胆汁酸非依赖性和碳酸氢盐依赖性的胆汁分泌；这些发现提示神经肽可能作用于特定的脑核，以调节肝功能。