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

肝非实质细胞可归因于肝缺血再灌注（I/R）损伤。肝星状细胞（hsc）的作用尚未得到很好的研究。我们使用已知可诱导造血干细胞凋亡的胶质毒素检测了造血干细胞的剥夺是否会影响肝脏I/R的强度。采用神经胶质毒素处理组和未处理组观察神经胶质毒素预处理对肝脏的体内影响。大鼠腹腔注射胶质毒素。采用胶质原纤维酸性蛋白（glial fibrillary acid protein， GFAP）免疫组化染色研究造血干细胞的数量。通过测定肝组织中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。Pringle手法诱导全肝缺血30min，再灌注6h。检测治疗组和非治疗组血清谷草转氨酶（AST）和丙氨酸转氨酶（ALT）水平，评价肝I/R损伤程度。胶质毒素处理显著降低肝脏中gfap阳性细胞的百分比。治疗组与未治疗组肝脏1、2区肝窦直径无差异。然而，在第3区，治疗组的正弦曲线比未治疗组宽。治疗组I/R后肝损伤明显受到抑制。胶质毒素治疗显著降低了体内造血干细胞的数量。胶质毒素预处理可预防肝I/R损伤。虽然需要进一步的研究，但第3区窦波的扩张可能有助于I/R后微循环的改善。提示造血干细胞在肝脏I/R损伤中也发挥了功能作用，剥夺造血干细胞可能是改善肝胆手术后肝损伤的一种新策略。

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.