Rapamycin inhibits hepatic stellate cell proliferation in vitro and limits fibrogenesis in an in vivo model of liver fibrosis
Rapamycin inhibits hepatic stellate cell proliferation in vitro and limits fibrogenesis in an in vivo model of liver fibrosis
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DOI：
10.1016/s0016-5085(99)70406-3
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发表时间：
1999-11-01
期刊：
影响因子：
29.4
通讯作者：
Zern, MA
中科院分区：
文献类型：
--
作者：
Zhu, JL;Wu, J;Zern, MA
背景与目的：肝移植术后肝纤维化进程加快是临床上的一个主要问题。这种反应可能是由抗排斥治疗引起的，在早期的报告中，我们表明FK-506在体内和体外肝纤维化模型中增强了纤维化过程。本研究的目的是确定一种新的免疫抑制剂雷帕霉素是否能增强或抑制肝纤维化。研究方法：在大鼠肝纤维化的四氯化碳模型和体外肝星状细胞增殖中研究雷帕霉素的作用。结果如下：通过组织学分析、胶原含量、前胶原和转化生长因子pi的信使RNA水平以及组织转氨酶活性测定，雷帕霉素抑制纤维形成大鼠模型中的细胞外基质沉积。此外，雷帕霉素降低血小板生长因子诱导的肝星状细胞增殖。结论：这些发现表明，新的抗排斥药物雷帕霉素抑制肝纤维化，因此可能成为一个有价值的除了免疫抑制剂的医疗设备。
Background & Aims: The accelerated course of hepatic fibrosis that occurs in some patients after liver transplantation is a major clinical problem. This response may be caused by the antirejection therapeutics, and in an earlier report we showed that FK-506 enhanced the fibrogenic process in in vivo and in vitro models of liver fibrosis. In the present study, the aim was to determine whether a new immunosuppressive agent, rapamycin, enhances or inhibits liver fibrosis. Methods: Effects of rapamycin were investigated in a carbon tetrachloride model of hepatic fibrosis in rats and on hepatic stellate proliferation in vitro. Results: Rapamycin inhibited extracellular matrix deposition in the rat model of fibrogenesis as determined by histological analysis, collagen content, messenger RNA levels of procollagen and transforming growth factor pi, and tissue transglutaminase activity. Moreover, rapamycin decreased platelet growth factor-induced proliferation of hepatic stellate cells. Conclusions: These findings indicate that the new antirejection agent rapamycin inhibits hepatic fibrosis and thus may become a valuable addition to the immunosuppression armamentarium.