Salvia Miltiorrhiza Ameliorates Liver Fibrosis by Activating Hepatic Natural Killer Cells in Vivo and in Vitro.
Salvia Miltiorrhiza Ameliorates Liver Fibrosis by Activating Hepatic Natural Killer Cells in Vivo and in Vitro.
复制标题
丹参通过体内外激活肝自然杀伤细胞改善肝纤维化
DOI：
10.3389/fphar.2018.00762
复制
发表时间：
2018
影响因子：
5.6
通讯作者：
Liu C
中科院分区：
文献类型：
--
作者：
Peng Y;Yang T;Huang K;Shen L;Tao Y;Liu C
自然杀伤细胞（NK）以其杀死活化的肝星状细胞（hsc）的能力而闻名，这在患者和动物模型中都得到了证实。但在晚期肝损伤期，杀伤功能下降。丹参是一种活血化瘀的中草药，在临床上被广泛用于治疗肝纤维化。然而，其免疫学机制尚不清楚。在此，我们提出SM的抗纤维化作用可能与促进肝NK细胞的活化有关。采用四氯化碳（CCl4）诱导肝纤维化，研究SM对NK细胞和HSC （JS-1细胞系，HSC）的体内外作用。从C57BL/6小鼠中分离肝NK细胞，在与造血干细胞共培养前与SM预孵育。我们发现SM在体内和体外均能增加NK细胞的频率，增强NKG2D和Nkp46对NK细胞的活性，抑制hsc的活化。SM在体外与hsc共培养前后通过增加NKG2D和IFN-γ的表达来促进NK细胞的活性。SM能部分拮抗asgm -1诱导的NK细胞衰竭，增强细胞活性，抑制hsc的体外活化。因此，我们的工作为SM在体内和体外通过增强NK细胞活性来减轻肝纤维化的抗纤维化机制提供了新的视角。
Natural killer (NK) cells are known for their ability to kill activated hepatic stellate cells (HSCs), which has been confirmed both in patients and animal models. But the killing function is depressed in period of advanced liver injury. Salvia Miltiorrhiza (SM), a Chinese herbal medicine for invigorating blood circulation and eliminating stasis, is widely used to treat liver fibrosis in clinic. Nevertheless, the immunological mechanism remains unclearly. Here, we put forward the hypothesis that the anti-fibrotic effect of SM is concerned with boosting the activation of hepatic NK cells. Liver fibrosis was induced with carbon tetrachloride (CCl4) and effects of SM on NK cells and HSC (JS-1 cell line, HSC) were investigated in vivo and in vitro. Hepatic NK cells were isolated from C57BL/6 mice, and pre-incubated with SM before they were co-cultured with HSCs. We found that SM increased frequency of NK cells, enhanced activities of NKG2D and Nkp46 on NK cells and inhibited activation of HSCs in vivo and in vitro. SM could promote the activities of NK cells by increasing the expressions of NKG2D and IFN-γ before or after co-cultured with HSCs in vitro. Besides, SM could partially antagonize ASGM-1-induced NK cell depletion and enhance the cell activities to inhibit HSCs activation in vitro. Therefore, our work provided a new insight into the anti-fibrotic mechanism that SM could enhance the activities of NK cell to reduce liver fibrosis in vivo and in vitro.
登录
查看更多内容
影响因子：
82.9
作者：
Mehal, Wajahat Z.;Iredale, John;Friedman, Scott L.
通讯作者：
Friedman, Scott L.
影响因子：
2.9
作者：
JAMALL, IS;FINELLI, VN;HEE, SSQ
通讯作者：
HEE, SSQ
影响因子：
4.3
作者：
Zhou, Yongqiang;Li, Weize;Chen, Lvyi
通讯作者：
Chen, Lvyi
影响因子：
25.7
作者：
Wasser, S;Ho, JMS;Tan, CEL
通讯作者：
Tan, CEL
影响因子：
13.5
作者：
Jeong, Won-Il;Park, Ogyi;Suh, Yang-Gun;Byun, Jin-Seok;Park, So-Young;Choi, Earl;Kim, Ja-Kyung;Ko, Hyojin;Wang, Hua;Miller, Andrew M.;Gao, Bin
通讯作者：
Gao, Bin