Hepatic Stellate Cells Play a Functional Role in Exacerbating Ischemia-Reperfusion Injury in Rat Liver

• Published in: European surgical research Vol. 60; no. 1-2; p. 74
• Main Authors: Takahashi, Tomokazu, Yoshioka, Masato, Uchinami, Hiroshi, Nakagawa, Yasuhiko, Otsuka, Naohiko, Motoyama, Satoru, Yamamoto, Yuzo
• Format: Journal Article
• Language: English
• Published: Switzerland 01.01.2019
• Subjects: Animals; Glial Fibrillary Acidic Protein - analysis; Gliotoxin - pharmacology; Hepatic Stellate Cells - drug effects; Hepatic Stellate Cells - physiology; Kupffer Cells - drug effects; Liver - blood supply; Male; Microcirculation - drug effects; Rats; Rats, Sprague-Dawley; Reperfusion Injury - etiology; Ischemia-reperfusion injury; Stellate cell; Liver; Sinusoidal perfusion; Gliotoxin
• ISSN: 1421-9921
• DOI: 10.1159/000499750

The involvement of hepatic stellate cells (HSCs) with ischemia-reperfusion (I/R) injury in rat liver was examined using gliotoxin, which is known to induce HSC apoptosis. Male Sprague-Dawley rats were used. HSC was represented by a glial fibrillary acidic protein (GFAP)-positive cell. Liver ischemia was produced by cross-clamping the hepatoduodenal ligament. The degree of I/R injury was evaluated by a release of aminotransferases. Sinusoidal diameter and sinusoidal perfusion rates were examined using intravital fluorescence microscopy. Gliotoxin significantly decreased the number of GFAP-positive cells 48 h after dosing (2.50 ± 0.19% [mean ± SD] in the nontreated group vs. 1.91 ± 0.46% in the gliotoxin-treated group). Liver damage was significantly suppressed by the pretreatment with gliotoxin. Sinusoidal diameters in zone 3 were wider in the gliotoxin group (10.25 ± 0.35 µm) than in the nontreated group (8.21 ± 0.50 µm). The sinusoidal perfusion rate was maintained as well in the gliotoxin group as in normal livers, even after I/R. Pretreatment with gliotoxin significantly reduced the number of HSCs in the liver and further suppressed liver injury following I/R. It is strongly suggested that HSCs play a functional role in exacerbating the degree of I/R injury of the liver.