Fasudil prevents liver fibrosis via activating natural killer cells and suppressing hepatic stellate cells.
Fasudil prevents liver fibrosis via activating natural killer cells and suppressing hepatic stellate cells.
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DOI：
10.3748/wjg.v27.i24.3581
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发表时间：
2021-06-28
影响因子：
4.3
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Han QJ;Mu YL;Zhao HJ;Zhao RR;Guo QJ;Su YH;Zhang J
法舒地尔是一种RAS同源家族成员A(RhoA)激酶抑制剂，临床上用于改善脑微循环，促进神经再生。越来越多的证据表明，抑制Rho-Kinase可以改善肝纤维化。目的：评价法舒地尔在硫代乙酰胺(TAA)诱导的小鼠肝纤维化模型中的抗肝纤维化作用。给C57BL/6小鼠灌胃TAA，每3d 1次，共12次。TAA诱导后1wk，每天1次，连续3wk，苏木精伊红染色、天狼星红染色、Western blotting、定量聚合酶链式反应(QPCR)检测免疫细胞活性。体外实验检测法舒地尔对肝星状细胞和自然杀伤(NK)细胞的影响。首先，我们发现法舒地尔对TAA诱导的肝损伤有保护作用，天狼星红染色阳性面积和I型胶原沉积明显减少。免疫印迹和定量聚合酶链式反应分析表明，法舒地尔可抑制α-SMA、MMP2、MMP9和转化生长因子β1(TGF1)的表达。此外，流式细胞仪分析表明，法舒地尔在体内和体外均能激活NK细胞。此外，法舒地尔通过降低α-SMA和β-1的表达，直接促进肝星状细胞的凋亡和抑制其增殖。法舒地尔通过激活NK细胞和阻断肝星状细胞的激活来抑制肝纤维化，从而为临床治疗肝纤维化提供了一种可行的方案。
Fasudil, as a Ras homology family member A (RhoA) kinase inhibitor, is used to improve brain microcirculation and promote nerve regeneration clinically. Increasing evidence shows that Rho-kinase inhibition could improve liver fibrosis. To evaluate the anti-fibrotic effects of Fasudil in a mouse model of liver fibrosis induced by thioacetamide (TAA). C57BL/6 mice were administered TAA once every 3 d for 12 times. At 1 wk after induction with TAA, Fasudil was intraperitoneally injected once a day for 3 wk, followed by hematoxylin and eosin staining, sirius red staining, western blotting, and quantitative polymerase chain reaction (qPCR), and immune cell activation was assayed by fluorescence-activated cell sorting. Furthermore, the effects of Fasudil on hepatic stellate cells and natural killer (NK) cells were assayed in vitro. First, we found that TAA-induced liver injury was protected, and the positive area of sirius red staining and type I collagen deposition were significantly decreased by Fasudil treatment. Furthermore, western blot and qPCR assays showed that the levels of alpha smooth muscle actin (α-SMA), matrix metalloproteinase 2 (MMP-2), MMP-9, and transforming growth factor beta 1 (TGF-β1) were inhibited by Fasudil. Moreover, flow cytometry analysis revealed that NK cells were activated by Fasudil treatment in vivo and in vitro. Furthermore, Fasudil directly promoted the apoptosis and inhibited the proliferation of hepatic stellate cells by decreasing α-SMA and TGF-β1. Fasudil inhibits liver fibrosis by activating NK cells and blocking hepatic stellate cell activation, thereby providing a feasible solution for the clinical treatment of liver fibrosis.
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影响因子：
3.7
作者：
Nakano R;Ohira M;Yano T;Imaoka Y;Tanaka Y;Ohdan H
通讯作者：
Ohdan H
影响因子：
5.5
作者：
Li, Xiaoyan;Zhang, Min;Gao, Zhiliang
通讯作者：
Gao, Zhiliang
DOI：
10.4049/jimmunol.2001266
发表时间：
2021-04-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Pan W;Nagpal K;Suárez-Fueyo A;Ferretti A;Yoshida N;Tsokos MG;Tsokos GC
通讯作者：
Tsokos GC
影响因子：
25.7
作者：
Gandhi CR
通讯作者：
Gandhi CR
DOI：
10.1016/j.jvir.2018.03.007
发表时间：
2018-08-01
影响因子：
2.9
作者：
Gaba, Ron C.;Mendoza-Elias, Nasya;Schachtschneider, Kyle M.
通讯作者：
Schachtschneider, Kyle M.