Mechanism of hepatic sympathetic action on potentiating liver injury and the involvement of cytokines.

肝交感神经作用增强肝损伤的机制和细胞因子的参与。

基本信息

批准号：
08670180
负责人：
IWAI Masaru
金额：
$ 1.41万
依托单位：
Ehime University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

项目摘要

The effects of hepatic sympathetic nerves on acute liver damage and the involvement of cytokine were studied using perfused rat liver as ex vivo system.The results were as follows :1) Effects of hepatic nerve stimulation on acute liver damage : Rat livers were perfused in situ without recirculation under constant pressure after treatment with D-galactosamine to produce acute liver injury. Meassuring the activities of lactate dehydrogenase and aspartate aminotransferase in the effluent as markers of acute cell damage, electrical stimulation of hepatic nerves increased the leakage of these enzymes. Moreover, infusion of zymosan, an activator of kupffer cells, into the portal vein also increased the enzyme leakage like nerve stimulation. These result indicate that the activation of hepatic nerves potentiates acute liver injury and that hepatic non-parenchymal cells may be involved in the action of hepatic nerves.2) Noradrenaline overflow during nerve stimulation and receptor subtype : In … More perfused livers described above, noradrenaline overflow into the effluent was rapidly increased during nerve stimulation indicating that these nerves belong to sympathetic nervous system. On the other hand, the potentiation of acute liver damage caused by hepatic nerve stimulation was significantly inhibited by alpha-adrenergic blocker bunazosin hydrochloride, suggesting that the effects of hepatic sympathetic nerves are mainly mediated by alpha-adrenergic receptors.3) Bioassay of TNF-alpha output from perfused liver : Bioassy system of Tumor Necrosis Factor-alpha (TNF-alpha), Which is related with cell death of hepatocyte, was established using WEHI164-cell clone. TNF-alpha activity in the effluent was higher in galactosamine-treated liver than in normal liver. Moreover, electrical stimuration of hepatic sympathetic nerves rapidly increased TNF-alpha output in galactosamine-treated liver. These results suggest that production and release of TNF-alpha is increased in injured livers and regulated by hepatic sympathetic nerves, and that Kupffer cell is important for TNF-alpha production.4) Immunohistochemistry of TNF-alpha in the liver : Immunohistochemistry of TNF-alpha in the liver using anti-TNF-alpha antibodies showed that TNF-alpha was strongly stained in galactosamine-treated liver suggesting the increased production of this cytokine in injured liver.These results indicate that the activation of hepatic sympathetic nerves potentiates liver injury and that hepatic TNF-alpha has an important role in the action of hepatic nerves. Less

以大鼠肝脏为离体灌注系统，研究肝交感神经对急性肝损伤的影响以及细胞因子的参与，结果如下：1）肝神经刺激对急性肝损伤的影响：大鼠肝脏原位灌注用 D-半乳糖胺处理后，在恒定压力下不进行再循环，产生急性肝损伤，测量流出物中乳酸脱氢酶和天冬氨酸转氨酶的活性，作为急性细胞损伤的标志物，电刺激。此外，将库普弗细胞激活剂酵母聚糖注入门静脉也与神经刺激一样增加了酶的渗漏。这些结果表明，肝神经的激活会加剧急性肝损伤，从而导致肝脏损伤。非实质细胞可能参与肝神经的作用。2）神经刺激和受体亚型期间去甲肾上腺素溢出：在上述灌注肝脏中，神经刺激过程中溢出到流出液中的去甲肾上腺素迅速增加，表明这些神经属于交感神经系统。另一方面，α-肾上腺素能阻滞剂盐酸布那佐嗪显着抑制肝神经刺激引起的急性肝损伤。肝交感神经的作用主要由α-肾上腺素能受体介导。3) 灌注肝脏输出的TNF-α生物测定：肿瘤生物测定系统使用WEHI164细胞克隆建立了与肝细胞细胞死亡相关的坏死因子-α（TNF-α），半乳糖胺处理的肝脏中的TNF-α活性高于正常肝脏。半乳糖胺处理的肝脏中，肝交感神经的快速增加 TNF-α 输出。这些结果表明，受损肝脏中 TNF-α 的产生和释放增加，并受其调节。肝交感神经，并且库普弗细胞对于强强产生很重要。4) 肝脏中 TNF-α 的免疫组织化学：使用抗 TNF-α 抗体对肝脏中 TNF-α 进行免疫组织化学显示，TNF-α 在半乳糖胺中染色-处理过的肝脏表明受损肝脏中这种细胞因子的产生增加。这些结果表明肝交感神经的激活会加剧肝损伤，并且肝TNF-α对肝神经的作用有重要作用。