Platelets contribute to the reduction of liver fibrosis in mice
Platelets contribute to the reduction of liver fibrosis in mice
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DOI：
10.1111/j.1440-1746.2008.05497.x
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发表时间：
2009-01-01
影响因子：
4.1
通讯作者：
Ohkohchi, Nobuhiro
中科院分区：
文献类型：
--
作者：
Watanabe, Motonobu;Murata, Soichiro;Ohkohchi, Nobuhiro
背景和目的：最近的一些研究报道，肝硬化（LC）可以改善，但很少有足够的策略，可用于对抗肝纤维化。虽然LC临床表现为血小板减少和脾功能亢进，但其与肝纤维化和血小板的关系尚不清楚。方法：C57 BL 6雌性小鼠腹腔注射四氯化碳（CCl 4）1 mL/kg，每周2次，共8周，诱导肝纤维化。除了CCl 4中毒外，还通过给予血小板生成素或脾切除术实现血小板增多。在8周，全血和肝脏标本获得的研究如下：外周血小板计数，组织病理学检查，羟脯氨酸含量测定，免疫染色，定量mRNA表达，和microarray analysis.Results：血小板增多症显着降低肝纤维化和肝组织羟脯氨酸含量相比，单独与四氯化碳管理的小鼠。血小板减少抑制了肝脏中转化生长因子-β mRNA表达的增加，并增加了基质金属蛋白酶-9的表达。肝脏的微阵列分析显示，血小板上调基因表达参与细胞增殖相比，表达在四氯化碳中毒的小鼠单独。血小板还增加了肝体积，增殖细胞核抗原标记指数，有丝分裂指数在fibrotic mice.Conclusion：这些结果清楚地表明，血小板减少肝纤维化，促进肝再生，即使在寒冷的条件下。因此，我们建议血小板可以提供一个有效的工具，在治疗肝硬化。
Background and Aim: Several recent studies have reported that liver cirrhosis (LC) can be ameliorated, but few adequate strategies are available against liver fibrosis. Although LC clinically shows thrombocytopenia and hypersplenism, the correlation with liver fibrosis and platelets remains unclear. The aim of the present study was to investigate the effect of platelets on liver fibrosis in mouse models.Methods: To induce liver fibrosis, C57BL6 female mice were injected i.p. with 1 mL/kg carbon tetrachloride (CCl4) twice a week for 8 weeks. Thrombocytosis was achieved by giving thrombopoietin or splenectomy in addition to CCl4 intoxication. At 8 weeks, whole blood and liver specimens were obtained for studies as follows: peripheral platelet counts, histopathological examination, hydroxyproline assay, immunostaining, quantification of mRNA expression, and microarray analysis.Results: Thrombocytosis significantly reduced liver fibrosis and hydroxyproline content of liver tissues compared to mice with CCl4 administration alone. Platelets suppressed increments in mRNA expression for transforming growth factor-beta, and increased matrix metalloproteinase-9 expression in the liver. Microarray analysis of the liver revealed that platelets upregulated gene expressions involved in cell proliferation compared to expression in mice with CCl4 intoxication alone. Platelets also increased liver volume, proliferative cell nuclear antigen labeling index, and mitotic index in fibrotic mice.Conclusion: These results clearly show that platelets reduce liver fibrosis and promote liver regeneration, even under cirrhotic conditions. We, therefore, propose that platelets could offer a potent tool in the treatment of liver cirrhosis.