Yiguanjian decoction inhibits macrophage M1 polarization and attenuates hepatic fibrosis induced by CCl(4)/2-AAF.
Yiguanjian decoction inhibits macrophage M1 polarization and attenuates hepatic fibrosis induced by CCl(4)/2-AAF.
复制标题
一贯煎汤抑制巨噬细胞M1极化，减轻CCl4/2-AAF诱导的肝纤维化。
DOI：
10.1080/13880209.2021.1961820
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发表时间：
2021-12
影响因子：
3.8
通讯作者：
Mu Y
中科院分区：
文献类型：
--
作者：
Xu Y;Xu W;Liu W;Chen G;Jiang S;Chen J;Jian X;Zhang H;Liu P;Mu Y
本课题组前期研究表明一贯煎具有抗肝纤维化作用，并能调节巨噬细胞状态。目的：探讨愈肝煎对巨噬细胞的调节作用机制。雄性Wistar大鼠用四氯化碳（CCl_4）诱导肝硬化12周，最后4周用2-乙酰氨基芴（2-AAF）诱导肝硬化。连续4周灌胃YGJ（3.56 mg/kg），对照组给予索拉（1 mg/kg）。体外实验中，用脂多糖（LPS）处理RAW 264. 7细胞，诱导巨噬细胞向M1表型极化，并将其与WB-F344细胞共培养，分为M组、YGJ组（2 μg/mL）和WIF-1组（1 μg/mL），以未处理细胞为对照。观察YGJ对WB-F344细胞的分化方向的影响。检测病理学、纤维化相关细胞因子、巨噬细胞极化相关成分和Wnt信号通路成分。在体内，与2-AAF/CCl 4组相比，YGJ组α-SMA、Col（1）、OV 6、SOX 9、EpCAM和M1巨噬细胞相关成分（STAT 1、IRF 3、IRF 5、IRF 8、SOCS 3）的表达水平显著降低（p < 0.01或0.05）。体外实验中，与M组相比，YGJ组RAW 264. 7细胞中M1巨噬细胞相关成分STAT 1、NF-κB、IRF 3、IRF 5和SOCS 3的表达水平显著降低（p < 0.05或p < 0.01）。YGJ组Wnt 3A、FZD 5、LRP-5/-6和β-catenin的表达水平较M组显著升高（p < 0.05或p < 0.01）。此外，与M组相比，YGJ组的Wnt-4/-5A/-5B和FZD 2的表达水平显著降低（p < 0.05或p < 0.01）。提示愈肝煎抗肝硬化作用与其抑制巨噬细胞M1极化有关，为愈肝煎的临床应用提供了科学依据。
Our previous studies indicated that Yiguanjian decoction (YGJ) has an anti-hepatic-fibrosis effect and could regulate macrophage status. To elucidate the mechanism of YGJ in regulating macrophages. Liver cirrhosis was induced by CCl4 for 12 weeks combined with 2-acetylaminofluorene (2-AAF) for the last 4 weeks in male Wistar rats. YGJ (3.56 mg/kg) orally administered in the last 4 weeks, and SORA (1 mg/kg) as control. In vitro, RAW264.7 cells were treated with lipopolysaccharides (LPSs) to induce macrophage polarization to the M1 phenotype, and they were co-cultured with WB-F344 cells and allocated to M group, YGJ group (2 μg/mL) and WIF-1 group (1 μg/mL) with untreated cells as control. The differentiation direction of WB-F344 cell line was observed in the presence or absence of YGJ. Pathology, fibrosis-related cytokines, macrophage polarization-related components, and Wnt signalling pathway components were detected. In vivo, the expression levels of α-SMA, Col (1), OV6, SOX9, EpCAM and M1 macrophage-related components (STAT1, IRF3, IRF5, IRF8, SOCS3) significantly decreased in the YGJ group compared with those in the 2-AAF/CCl4 group (p < 0.01 or 0.05). In vitro, the expression levels of M1 macrophage-related components, including STAT1, NF-κB, IRF3, IRF5, and SOCS3, in RAW264.7 cells decreased significantly in the YGJ group compared with those in the M group (p < 0.05 or p < 0.01). The expression levels of Wnt3A, FZD5, LRP-5/-6, and β-catenin significantly increased in the YGJ group compared with those in the M group (p < 0.05 or p < 0.01). In addition, the expression levels of Wnt-4/-5A/-5B, and FZD2 significantly decreased in the YGJ group compared with those in the M group (p < 0.05 or p < 0.01). This study suggests that the anti-cirrhosis effect of YGJ is associated with its ability to inhibit macrophage M1-polarization, which provides a scientific basis for the clinical application of YGJ.
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DOI：
10.1186/1478-811x-11-29
发表时间：
2013-04-19
期刊：
Cell communication and signaling : CCS
影响因子：
--
作者：
Ploeger DT;Hosper NA;Schipper M;Koerts JA;de Rond S;Bank RA
通讯作者：
Bank RA
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
3.7
作者：
Chen J;Zhang X;Xu Y;Li X;Ren S;Zhou Y;Duan Y;Zern M;Zhang H;Chen G;Liu C;Mu Y;Liu P
通讯作者：
Liu P
影响因子：
64.8
作者：
Reya, T;Clevers, H
通讯作者：
Clevers, H
影响因子：
5.4
作者：
Lin, Hung-Jen;Chen, Jiun-Yu;Chen, Chuan-Mu
通讯作者：
Chen, Chuan-Mu