神经酰胺合酶-神经酰胺通路在青蒿琥酯抑制肝纤维化中的作用

doi:10.12047/j.cjap.5931.2020.061

中国应用生理学杂志 ›› 2020, Vol. 36 ›› Issue (3): 279-282.doi: 10.12047/j.cjap.5931.2020.061

神经酰胺合酶-神经酰胺通路在青蒿琥酯抑制肝纤维化中的作用

阮建佳^1△, 杜岩²

1. 天津市蓟州区人民医院综合内科,
2. 天津市蓟州区人民医院药剂科, 天津 301900

收稿日期:2019-08-29 修回日期:2020-03-26 发布日期:2020-09-25
通讯作者: Tel: 022-60733012; E-mail: wangyiaruan@163.com

Effects of artesunate on the inhibition of hepatic fibrosis through ceramide synthase-ceramide pathway

RUAN Jian-jia^1△, DU Yan²

1. Department of Comprehensive Internal Medicine,
2. Department of Pharmacy, Tianjin Jizhou District People's Hospital, Tianjin 301900, China

Received:2019-08-29 Revised:2020-03-26 Published:2020-09-25

摘要/Abstract

摘要： 目的: 探讨神经酰胺通路在青蒿琥酯(Art)抑制肝纤维化过程中的作用。方法: 将肝星状细胞(LX-2)分为细胞对照组、Art 350 μmol/L组、神经酰胺合酶阻断剂(FB1) 6 μmol/L组及FB1 6 μmol/L + Art 350 μmol/L合用组。每组7个复孔,作用24 h后,收集细胞及上清液进行检测。Western blot法测定神经酰胺合酶2(LASS2)、过氧化物酶体增殖物激活受体-γ(PPAR-γ)、Caspase-3蛋白的表达, HPLC-FLD法对神经酰胺(Cer)的含量进行测定,MTT法检测LX-2的增殖情况,酶消化法检测羟脯氨酸(Hyp)的含量。结果: 与细胞对照组比较,Art处理组神经酰胺合酶的蛋白表达、神经酰胺含量显著增加、LX-2细胞的增殖明显抑制、PPAR-γ和Caspase-3蛋白表达上调、羟脯氨酸分泌抑制 (P＜0.05);FB1处理组神经酰胺合酶的蛋白表达和神经酰胺含量显著降低、LX-2细胞增殖显著增加、PPAR-γ和Caspase-3蛋白表达下调、羟脯氨酸分泌增加(P＜0.05);与Art单用组比较,两药合用可显著降低Art对神经酰胺合酶蛋白的表达和神经酰胺含量升高的作用,减弱Art对LX-2细胞增殖、PPAR-γ、Caspase-3蛋白表达及羟脯氨酸分泌的作用(P＜0.05)。结论: 青蒿琥酯可通过神经酰胺合酶-神经酰胺通路增加细胞中神经酰胺水平,发挥抑制肝纤维化的作用。

关键词: 肝纤维化, 神经酰胺, 神经酰胺合酶, 青蒿琥酯, 肝星状细胞

Abstract: Objective: To investigate the effects of ceramide pathway on the inhibition of artesunate (Art) to hepatic fibrosis.Methods: LX-2 cells were divided into control group, Art treated group with 350 μmol/L, fumonisin B1 (FB1) treated group with 6 μmol/L, and Co-administration group of artesunate 350 μmol/L and fumonisin B1 6 μmol/L. There were 7 compound holes in each group. After 24 hours of treatment, the cells and supernatant were collected and detected. The expressions of homo sapiens longevity assurance homologue 2 (LASS2), peroxisome proliferators-activated receptors-γ (PPAR-γ) and Caspase-3 were evaluated by Western blot, the content of ceramide was evaluated by HPLC-FLD method, MTT assay was adopted to measure the rate of proliferation of LX-2 cells. The content of hydroxyproline was determined by digestive method. Results: Compared with the control group, the expression of ceramide synthase protein and the ceramide content were increased significantly, the proliferation of LX-2 cells was inhibited significantly, the expressions of PPAR-γ and Caspase-3 protein were up-regulated and the secretion of hydroxyproline was inhibited in Art treated group (P＜0.05). In FB1 treated group, the protein expression of ceramide synthase and the ceramide content were decreased significantly, the proliferation of LX-2 cells was increased significantly, the expressions of PPAR-γ and Caspase-3 protein were down-regulated, and the secretion of hydroxyproline was increased (P＜0.05). Compared with the Art alone group, the combination of the two drugs could significantly reduce the effects of Art on the expression of ceramide synthase protein and the increase of ceramide content, and attenuate the effects of Art on the cell proliferation , PPAR-γ, Caspase-3 protein expression and hydroxyproline level of LX-2 cells (P＜0.05). Conclusion: Artesunate could inhibit hepatic fibrosis by increasing the content of ceramide through the ceramide synthase-ceramide pathway.

Key words: hepatic fibrosis, ceramide, synthase-ceramide, artesunate, LX-2

中图分类号:

R575.2

阮建佳, 杜岩. 神经酰胺合酶-神经酰胺通路在青蒿琥酯抑制肝纤维化中的作用[J]. 中国应用生理学杂志, 2020, 36(3): 279-282.

RUAN Jian-jia, DU Yan. Effects of artesunate on the inhibition of hepatic fibrosis through ceramide synthase-ceramide pathway[J]. CJAP, 2020, 36(3): 279-282.

参考文献

[1] Zhang X, Tan Z, Wang Y, et al. PTPRO-associated hepatic stellate cell activation plays a critical role in liver fibrosis[J]. Cell Physiol and Biochem, 2015, 35(3): 885-898.
[2] Zhu W, Wang X, Zhou Y, et al. C2-ceramide induces cell death and protective autophagy in head and neck squamous cell carcinoma cells[J]. Int J Mol Sci, 2014, 15 (2): 3336-3355.
[3] Mencarelli C, Martinez-Martinez P. Ceramide function in the brain: when a slight tilt is enough[J]. Cell Mol Life Sci, 2013, 70 (2): 181-203.
[4] Yang L, Zheng L, Tian Y, et al. C6 ceramide dramatically enhances docetaxel-induced growth inhibition and apoptosis in cultured breast cancer cells: A mechanism study[J]. Exp Cell Res, 2015, 332(1): 47-59.
[5] 娄婷婷, 李英娴, 方步武, 等. 测定生物样本中神经酰胺含量的HPLC-FLD法[J]. 药物分析杂志, 2012, 32(10): 1807-1812.
[6] 杜岩, 李立楠, 方步武. 青蒿琥酯抑制肝纤维化的作用及其机制[J]. 中国应用生理学杂志, 2015, 31(1): 14-17.
[7] Schiffmann S, Birod K, Mannich J, et al. Ceramide metabolism in mouse tissue[J]. Int J Biochem Cell Biol, 2013, 45(8): 1886-1894.
[8] Pewzner-Jung Y , Park H , Laviad EL , et al. A critical role for ceramide synthase 2 in liver homeostasis: I. Alterations in lipid metabolic pathways[J]. J Biol Chem, 2010, 285(14): 10902-10910.
[9] Larsen PJ, Tennagels N. On ceramides, other sphingolipids and impaired glucose homeostasis[J]. Mol Metab, 2014, 3(3): 252-260.
[10]Zhang F, Kong D, Lu Y, et al. Peroxisome proliferator-activated receptor-γ as a therapeutic target for hepatic fibrosis: from bench to bedside[J]. Cell Mol Life Sci, 2013, 70(2): 259-276.
[11]Wang Z, Xu JP, Zheng YC, et al. Peroxisome proliferator-activated receptor gamma inhibits hepatic fibrosis in rats[J]. Hepatobiliary Pancreat Dis Int, 2011, 10(1): 64-71.
[12]Li Y, Dong J, Ding T, et al. Sphingomyelin synthase 2 activity and liver steatosis an effect of ceramide-mediated peroxisome proliferator-activated receptor γ2 suppression[J]. Arterioscler Thromb Vasc Biol, 2013, 33(7): 1513-1520.
[13]Yu J, Shen BO, Chu ESH, et al. Inhibitory role of peroxisome proliferator-activated receptor gamma in hepatocarcinogenesis in mice and in vitro[J]. Hepatology, 2010, 51(6): 2008-2019.

神经酰胺合酶-神经酰胺通路在青蒿琥酯抑制肝纤维化中的作用

Effects of artesunate on the inhibition of hepatic fibrosis through ceramide synthase-ceramide pathway

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 8

编辑推荐

Metrics

本文评价

[1]	张倩璐, 旷昕. 丙泊酚对转化生长因子-β1诱导肝星状细胞激活的影响及其机制[J]. 中国应用生理学杂志, 2020, 36(3): 273-278.
[2]	罗怡爽, 郑秀婷, 章浩月, 徐丽萍, 裘加鹏, 徐港铭, 刘爱明. α-荼异硫氰酸酯诱导小鼠胆汁淤积性肝纤维化及其炎症通路^*[J]. 中国应用生理学杂志, 2020, 36(2): 152-156.
[3]	邵毅英, 范玉琪, 李思葳, 赵冰冰, 邵小婷, 扈敬, 徐长庆, 魏璨. CaSR表达在大鼠糖尿病性肝硬化损伤和纤维化发生中的作用[J]. 中国应用生理学杂志, 2020, 36(1): 1-5.
[4]	吴晨, 邱玉保, 孙雪倩, 陈丹, 吴亚先, 庞庆丰. 姜黄素对小鼠胆汁淤积性肝纤维化的改善作用及其机制研究^*[J]. 中国应用生理学杂志, 2019, 35(5): 468-472.
[5]	陈信信, 张晓芸, 丁玉真, 李鑫, 官秀梅, 李宏, 成敏, 崔晓栋. 剪切应力环境下的内皮祖细胞对肝星状细胞增殖和生物功能的影响[J]. 中国应用生理学杂志, 2018, 34(5): 404-407.
[6]	王志旺, 付晓艳, 程小丽, 包小英, 刘雪枫, 段海婧. 育阴软肝颗粒剂对肝纤维化大鼠TGF-β1表达的影响[J]. 中国应用生理学杂志, 2018, 34(2): 169-172.
[7]	赵志欣, 李腊梅, 蒋恩社. 神经鞘磷脂合成酶2缺乏对小鼠学习记忆能力的影响[J]. 中国应用生理学杂志, 2017, 33(2): 155-158.
[8]	肖敏, 屈小虎, 吕聚坪, 史杨, 李长西, 谢克俭. 吡非尼酮对四氯化碳诱导的小鼠肝纤维化的影响[J]. 中国应用生理学杂志, 2016, 32(4): 378-382.