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

2001 Fiscal Year Final Research Report Summary

• Project/Area Number: 11671242
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Yamaguchi University
• Principal Investigator: FUKUMOTO Yohei Yamaguchi University, Hospital, Professor, 医学部附属病院, 教授 (90136193)
• Co-Investigator(Kenkyū-buntansha): SAKAIDA Isao Yamaguchi University, Hospital, Research Associate, 医学部・附属病院, 助手 (80263763) ; MURAKAMI Fujio Yamaguchi University, Hospital, Lecturer, 医学部・附属病院, 講師 (10253155) ; TATEISHI Akio Yamaguchi University, Hospital, Associate Prof., 医学部・附属病院, 助教授 (00155102) ; KAYANO Kouzou Yamaguchi University, Hospital, Research Associate, 医学部, 助手 (90314799)
• Project Period (FY): 1999 – 2000
• Keywords: Jaundice / SIRS / Cytokine / Bile production / Bile acid / Chenodeoxycholic acid / Secretin

Research Abstract

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.