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The investigation on the relation between the glutathione metabolism and liver atrophy.

谷胱甘肽代谢与肝萎缩关系的研究。

基本信息

批准号：
02454316
负责人：
KOBAYASHI Nobuaki
金额：
$ 2.94万
依托单位：
Ehime University (1991)Kyoto University (1990)
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1991
项目状态：
已结题

项目摘要

Investigation on the giutathione metaboism during the process for liver atrophy.This research was focused upon the changes of glutathione metabolism, which is considered to work as a scavenger, in consequence of hepatic repercusion.1. (Method)Wistar rats were divided to two groups, experimental group ; superior nescntcric vein (SMV) was clamped for 30 min and then deciampcd. I ; Sham operation group ; simple laparotomy was donc. In each group, GSH and GSSG were measured enzymatically in liver tissue, scrum from supra hepatic inferior vena cava (IVC) and bile sample, and adenine nucleotistes were measured enzymatically and energy charge (EC)was calculated by mean of Atkins.(Results)GSH and GSSG in liver tissue after SMV clamping and reperfusion did not change, while GSH and GSSG level in supra hepatic IVC increased signifcantly (about 2 times in GSH and over 3 times in GSSG) compared with Sham operation group 10 min after 10 min SHV clamp, and these high level of glutathiones were kept until 120 min after SMV clamp for 30 min. Binary GSH and GSSG level decreased consequently after SMV clamp and reelevated after reperfusion. Hepatic ATP and EC decreased in consequence of SMV clamp and then recovered 10 min after reperfusion.(Discussion).It is considered that the hepatic GSII/GSSG ratio is maintained by releasing GSSG generated by oxidant stress from liver tissue.The changes of GSSG level in bile is correlated to the changes of ATP and EC, and it is considered to depend on ATP. The change of GSSG level in scrum precede those of transaminases.2. In relation to these ressearch, the relation between cytokines (TNF-alpha, ILl-beta) and hypermetabolic state in compernsatory phase of liver were investigated in rats. By systematic administration of TNF-alpha and ILl-beta, hepatic mitochondrial redox state was restored and ketogenesis was suppresscd. EC decreased by increased energy demand.

肝萎缩过程中谷胱甘肽代谢的研究本研究主要探讨肝再灌注过程中谷胱甘肽代谢的变化.（方法）Wistar大鼠分为实验组和对照组，实验组夹闭上级肠系膜静脉（SMV）30 min后，再行去心复律。I组：假手术组，单纯开腹手术。各组分别取肝组织、肝上下腔静脉（IVC）积液和胆汁，酶法测定GSH和GSSG，酶法测定腺嘌呤核苷酸，用阿特金斯法计算能荷（EC）。结果SMV阻断再灌注后肝组织GSH、GSSG含量无明显变化，肝上下腔静脉GSH、GSSG含量明显升高SHV钳夹10 min后10 min，GSH约为假手术组的2倍，GSSG约为假手术组的3倍以上，SMV钳夹30 min后，GSH和GSSG水平明显下降，再灌注后恢复。SMV钳夹后肝ATP和EC下降，再灌注10 min后恢复。（讨论）.认为肝脏GSII/GSSG比值是通过从肝组织释放氧化应激产生的GSSG来维持的，胆汁中GSSG水平的变化与ATP和EC的变化相关，并被认为依赖于ATP。血清GSSG水平的变化先于转氨酶水平的变化.在此基础上，本文还研究了TNF-α、IL-1-β等细胞因子与大鼠肝代谢的关系。通过系统给予TNF-α和IL-1-β，肝线粒体氧化还原状态恢复，生酮被抑制。能源需求增加导致EC下降。