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，黄疸的出现是常见的，但其发生机制尚不清楚，黄疸的治疗更为困难。为探讨内源性高细胞因子血症与黄疸的关系，研究了SIRS患者和非SIRS患者的黄疸发生率，并尝试通过给予SIRS患者的血清来制备黄疸大鼠模型。结果，与无SIRS的28.6%相比，在有SIRS的患者中97.8%显著观察到黄疸。近年来对胆汁流动、胆汁酸和微管系统的研究进展表明，核受体调控胆汁酸转运蛋白在肝细胞膜上的出现，而鹅去氧胆酸（chenodeoxycholic acid，CDCA）是肝细胞核的配体之一。此外，分泌素，一种胃肠激素，最近报道，诱导顶端插入的水通道的胆管细胞质膜上的微管系统。作为下一项研究，在给予和不给予胰泌素的CDCA或脱氧胆酸（DCA）大鼠模型中评价胆汁流量、胆汁酸和碳酸氢盐的胆汁排泄的变化。虽然大容量的TDCA或DCA负荷导致胆汁体积和胆汁中胆汁酸和碳酸氢盐的排泄减少，但胰泌素阻止胆汁流量的减少并促进胆汁酸和碳酸氢盐的排泄。提示CDCA在肝细胞DNA水平上调节胆汁的流动，促胰液素在胆汁分泌过程中也影响胆汁酸代谢。此外，促胰液素显示出在治疗黄疸中产生潜在作用。

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.