Deprivation of hepatic stellate cells prevents ischemia-reperfusion injury of the liver

剥夺肝星细胞可预防肝脏缺血再灌注损伤

基本信息

批准号：
18591498
负责人：
SHIBATA Satoshi
金额：
$ 2.5万
依托单位：
Akita University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591498/
关键词：
ischemia reperfusion iniury gliotoxin hepatic stellate cells liver 外科 K_<ATP> channel 細胞保護

项目摘要

Hepatic non-parenchymal cells are attributable to ischemia-reperfusion (I/R) injury of the liver. The contribution of hepatic stellate cells (HSCs) is not well studied. We examined whether the deprivation of HSCs affected the strength of I/R of the liver using gliotoxin that was known to induce apoptosis of HSCs.The in vivo effect of gliotoxin pretreatment on the liver was examined in the gliotoxin-treated group and non-treated group. Gliotoxin was administered to rats intraperitoneally. The number of HSCs was studied by immunohistochemical staining of glial fibrillary acidic protein (GFAP), a marker of HSCs. The proportion of GFAP-positive cells to total cells in the liver was evaluated by measuring the stained. Changes in sinusoidal diameter were examined using intravital fluorescence microscopy. Total hepatic ischemia of 30 minutes was induced by Pringle's maneuver and followed by reperfusion of 6 hours. Serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured to evaluate the I/R injury of the liver in the treated group and the non-treated group.Gliotoxin treatment significantly decreased the percentage of GFAP-positive cells in the liver. There was no difference in hepatic sinusoidal diameters between the treated and the non-treated groups in zones 1,2 of the liver. However, in zone 3, the sinusoids were wider in the treated group than the non-treated group. Liver damage after I/R was significantly suppressed in the treated group.Treatment with gliotoxin significantly decreased the number of HSCs in vivo. Pretreatment with gliotoxin prevented I/R injury of the liver. Although a further study is necessary, dilation of the sinusoids in zone 3 might contribute to improving the microcirculation after I/R. It was suggested that HSCs also played a functional role in the I/R injury of the liver and their deprivation might be a novel strategy for ameliorating the liver damage after hepatobiliary surgery.

肝非实质细胞可归因于肝脏缺血再灌注（I/R）损伤。肝星状细胞（HSC）的贡献尚未得到充分研究。我们使用已知可诱导 HSC 凋亡的胶霉毒素检查了 HSC 的剥夺是否会影响肝脏 I/R 的强度。在胶霉毒素治疗组和未治疗组中检查了胶霉毒素预处理对肝脏的体内影响团体。对大鼠腹膜内施用胶霉毒素。通过对 HSC 的标记物——胶质纤维酸性蛋白 (GFAP) 进行免疫组织化学染色来研究 HSC 的数量。通过测量染色来评估肝脏中 GFAP 阳性细胞占总细胞的比例。使用活体荧光显微镜检查正弦直径的变化。通过 Pringle 操作诱发 30 分钟的全肝缺血，然后再灌注 6 小时。检测治疗组和未治疗组的血清天冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT）水平以评估肝脏I/R损伤情况。胶霉毒素治疗显着降低了治疗组中GFAP阳性细胞的百分比肝。治疗组和未治疗组在肝脏 1,2 区的肝窦直径没有差异。然而，在 3 区，治疗组的正弦波比未治疗组更宽。治疗组中 I/R 后的肝损伤明显受到抑制。胶霉毒素治疗显着减少了体内 HSC 的数量。用胶霉毒素预处理可防止肝脏缺血再灌注损伤。尽管需要进一步研究，但第 3 区正弦波的扩张可能有助于改善 I/R 后的微循环。有人提出，HSC 在肝脏 I/R 损伤中也发挥着功能作用，其剥夺可能是改善肝胆手术后肝脏损伤的一种新策略。