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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.

肝脏非实质细胞是肝脏缺血再灌注损伤的重要原因。肝星状细胞（HSC）的贡献还没有得到很好的研究。我们使用已知可诱导HSCs凋亡的gliotoxin检测HSCs剥夺是否影响肝脏I/R的强度，在gliotoxin处理组和未处理组中检测gliotoxin预处理对肝脏的体内作用。对大鼠腹腔注射胶粘毒素。用免疫组化方法检测胶质细胞酸性蛋白（GFAP）的表达。通过测量染色的GFAP阳性细胞与肝中总细胞的比例来评估。使用活体荧光显微镜检查正弦直径的变化。用Pringle法造成全肝缺血30分钟，然后再灌注6小时。结果表明，Gliotoxin处理组和对照组大鼠肝脏I/R损伤程度不同，Gliotoxin处理组大鼠肝脏GFAP阳性细胞数明显减少，而Gliotoxin处理组大鼠肝脏GFAP阳性细胞数明显减少。肝窦直径在处理组和未处理组之间在肝脏的1区、2区没有差异。然而，在3区中，处理组的窦状隙比未处理组宽。胶质毒素治疗组能显著抑制肝缺血再灌注后肝细胞的损伤，并能显著减少肝星状细胞的数量。用胶霉毒素预处理可防止肝脏I/R损伤。尽管需要进一步研究，但扩张3区血窦可能有助于改善I/R后微循环。提示肝星状细胞在肝脏I/R损伤中也发挥了一定的作用，去除肝星状细胞可能是改善肝胆术后肝脏损伤的一种新策略。