Studies for a new mechanism of jaundice ; Analysis of an appearance of jaundice in SIRS case

在脓毒症和全身炎症反应综合征(SIRS)患者的临床过程中，经常会发现黄疸的出现，但其发生机制尚不清楚，治疗难度较大。为探讨内源性高细胞分裂素血症与黄疸的关系，研究了SIRS患者和非SIRS患者的黄标率，并尝试用SIRS患者的血清制作大鼠黄疸模型。结果发现，有SIRS的患者中有97.8%的患者出现黄疸，而无SIRS的患者中只有28.6%的患者出现黄疸。近年来，随着对胆汁流动、胆汁酸和微管系统的研究进展，发现核受体调节肝细胞膜上某些胆汁酸转运蛋白的出现，鹅去氧胆酸(CDCA)是肝细胞核的配体之一。此外，促胰液素是一种胃肠激素，最近被报道诱导与微管系统有关的胆管细胞质膜上的水通道的心尖插入。作为下一步的研究，在给予CDCA或脱氧胆酸(DCA)的大鼠模型中，观察给予促胰液素和不给予促胰液素的大鼠胆汁流量、胆汁酸和碳酸氢盐排泄量的变化。虽然大剂量的TDCA或DCA负荷导致胆汁体积减少，胆汁中胆汁酸和碳酸氢盐排泄减少，但促胰液素阻止了胆汁流量的减少，增加了胆汁中胆汁酸和碳酸氢盐的排泄。CDCA可能在肝细胞DNA水平上调节胆汁流量，促胰液素也影响胆汁分泌过程中的胆汁酸代谢。此外，促胰液素被证明在黄疸的治疗中产生了潜在的效果。

In the clinical course of the patients with sepsis and systemic inflammatory response syndrome (SIRS), an appearance of jaundice was frequently noticed, but the mechanism of its occurrence is still unknown and the treatment of jaundice is harder. To investigate the relationship between endogenous hypercytokinemia and jaundice, a rate of the presence of jaundice was studied in patients with and without SIRS, and a trial to make rat models with icterus by administrations of serum from SIRS's patients was attempted. As a result, jaundice was significantly observed at 97.8 % of the patient with SIRS as compared with at 28.6 % of that without SIRS. However, the rat model with icterus could not be detected using serum samples from SIRS's patients.With progress in recent studies regarding bile flow, bile acid and microtubles system, it was appeared that the nuclear receptor regulates the appearance of some transporter proteins for bile acid on the hepatic cell membrane, and that chenodeoxycholic acid (CDCA) was one of ligands to the nucleus. Moreover, secretin, a gastrointestinal hormone, was recently reported to induce the apical insertion of a water channel on the cholangiocyte plasma membrane in relation to microtubules system. As the next study, changes of bile flow, biliary excretions of bile acid and bicarbonate were evaluated in a CDCA or deoxycholic acid (DCA) given rat model with and without secretin administration. Although a large volume of TDCA or DCA load produced decreases of bile volume and excretions of bile acid and bicarbonate in bile, secretin prevented the decrease of bile flow and enhanced biliary excretions of bile acid and bicarbonate. It seemed that CDCA regulates bile flow on the DNA level of the hepatocyte, and that secretin also affects bile acid metabolism in bile secretary process. Moreover, secretin was shown to produce a potential effect in the treatment of jaundice.