Management of hepatic ischemia-reperfusion injury by suppressing the hepatic stellate cell activation.

2006 Fiscal Year Final Research Report Summary

• Project/Area Number: 17591367
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Akita University
• Principal Investigator: YOSHIOKA Masato Akita University, Gastroenterological Surgery, Assistant professor, 医学部, 助手 (40375275)
• Co-Investigator(Kenkyū-buntansha): SHIBATA Satoshi Akita University, Gastroenterological Surgery, Lecturer, 医学部, 講師 (40333934) ; SATO Tsutomu Akita University, Gastroenterological Surgery, Associate professor, 医学部, 助教授 (90235367) ; YAMAMOTO Yuzo Akita University, Gastroenterological Surgery, Professor, 医学部, 教授 (70281730)
• Project Period (FY): 2005 – 2006
• Keywords: Hepatic stellate cell / Ischemia-reperfusion injury / Microcirculation / Hepatic sinusoidal diameter / Kupffer cell

Research Abstract

Hepatic non-parenchymal cells are attributable to ischemia-reperfusion (I/R) injury of the liver. The participation of Kupffer cells and sinusoidal endothelial cells have been repeatedly documented. However, the contribution of hepatic stellate cells (HSCs) is not well studied. In this study, we examined whether the deprivation of HSCs affected the strength of I/R of the liver using Gliotoxin that was known to induced apoptosis of HSCs in vitro. Male SD rats were used. Gliotoxin was administered intraperitoneally with a dose of 3.0 mg/kg. The number of HSCs was studied by immunohistochemical staining of GFAP. The proportion of GFAP-positive cells to total cells in the liver was evaluated by measuring the stained areas. Changes in sinusoidal diameter and perfusion rate were examined by intravital fluorescence microscopy. Serum AST and ALT levels were measured to evaluate the I/R injury of the liver at 6 hours after reperfusion. As a result, the percentage of GFAP-positive cells (%) were 1.91±0.46 in Gliotoxin group and 2.50±0.19 in the control group. There was no significance in hepatic sinusoidal diameter in zones 1 and 2. However, in zone 3, the sinusoids were wider in the Gliotoxin group (10.28±0.43 μm) than the control group (8.04±0.45 μm). Hepatic sinusoidal perfusion rates (%) during I/R were decreased in Control group from 100 to 79.8±6.1. In contrast, in Gliotoxin group, those were kept from 99.9±0.2 to 99.8±0.7. The serum levels of AST and ALT (IU/L) were 298±148 and 121±50 in the Gliotoxin group, and 515±160 and 350±134 in the Control group. In conclusion, Gliotoxin significantly decreased the number of HSCs in vivo and resulted in keeping the sinusoidal microcirculation and preventing I/R injury of the liver.