Department of Haematology, Center of Excellence in Tissue Engineering, Henan Tumor Hospital, Zhengzhou University, 127 Dongming Road, Zhengzhou 450008, China.
Toxicology. 2010 Mar 30;270(1):43-8. doi: 10.1016/j.tox.2009.12.002. Epub 2009 Dec 11.
On the basis of the recent report that granulocyte colony-stimulating factor (G-CSF) administration after rats' partial orthotopic liver transplantation greatly improved survival rate and liver regeneration of partial graft, we here evaluated the effect of intermittent administration of G-CSF on fibrosis formation induced by carbon tetrachloride (CCl(4)). Bone marrow chimeric female C57BL/6 mice were treated with G-CSF at days 1, 7, 14, 21, and 28 after CCl(4) challenge. At day 35 after CCl(4) administration, we found that G-CSF treatment significantly reduced CCl(4)-induced liver damage and collagen deposition. In addition, levels of hepatic hydroxyproline and serum fibrosis markers in mice receiving G-CSF administration after CCl(4) challenge were significantly lower compared to those of control mice. Histological examination suggested that hepatic damage recovery was much better in these G-CSF-treated mice. Immunofluorescence and fluorescence in situ hybridization (FISH) analysis revealed that donor cells engrafted into host liver, had epithelium-like morphology and expressed albumin, although at low frequency. These results suggest that intermittent G-CSF treatment might initiate endogenous hepatic tissue regeneration in response to CCl(4) injury and ameliorate its fibrogenic effects.
基于最近的一份报告，粒细胞集落刺激因子（G-CSF）在大鼠部分原位肝移植后给药极大地提高了部分移植物的存活率和肝再生，我们在此评估了 G-CSF 间歇性给药对四氯化碳（CCl4）诱导的纤维化形成的影响。骨髓嵌合雌性 C57BL/6 小鼠在 CCl4 挑战后第 1、7、14、21 和 28 天接受 G-CSF 治疗。在 CCl4 给药后第 35 天，我们发现 G-CSF 治疗显著减轻了 CCl4 诱导的肝损伤和胶原沉积。此外，与对照组小鼠相比，接受 CCl4 挑战后给予 G-CSF 治疗的小鼠肝羟脯氨酸水平和血清纤维化标志物水平明显降低。组织学检查表明，这些接受 G-CSF 治疗的小鼠的肝损伤恢复情况要好得多。免疫荧光和荧光原位杂交（FISH）分析表明，供体细胞植入宿主肝脏后，具有上皮样形态并表达白蛋白，尽管频率较低。这些结果表明，间歇性 G-CSF 治疗可能会引发内源性肝组织再生以应对 CCl4 损伤，并减轻其纤维形成作用。
