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青蒿琥酯对结合型胆汁酸诱导小鼠原代肝细胞IL-6产生的机制研究
Artesunate reduces IL-6 production in primary mouse hepatocytes induced by conjugated bile acids through inhibiting p-p65 signaling pathway
- 第三军医大学学报 2021年43卷第12期 页码：1133-1139
- 作者机构：
400038 重庆 陆军军医大学第一附属医院消化内科胆汁淤积性肝病中心
- 作者简介：
[柴进，E-mail: jin.chai@cldcsw.org CHAI Jin, E-mail: jin.chai@cldcsw.org
- 基金信息：国家自然科学基金优秀青年科学基金(81922012)
DOI：10.16016/j.1000-5404.202012225
中图分类号： R654.3;R654.4;R931.6收稿：2020-12-28，
修回：2021-03-29，
纸质出版：2021-06-30
- 稿件说明：
移动端阅览
廖敏, 李璇, 张樑君, 等. 青蒿琥酯对结合型胆汁酸诱导小鼠原代肝细胞IL-6产生的机制研究[J]. 第三军医大学学报, 2021,43(12):1133-1139.
Min LIAO, Xuan LI, Liangjun ZHANG, et al. Artesunate reduces IL-6 production in primary mouse hepatocytes induced by conjugated bile acids through inhibiting p-p65 signaling pathway[J]. Journal of Third Military Medical University, 2021, 43(12): 1133-1139.
廖敏, 李璇, 张樑君, 等. 青蒿琥酯对结合型胆汁酸诱导小鼠原代肝细胞IL-6产生的机制研究[J]. 第三军医大学学报, 2021,43(12):1133-1139. DOI： 10.16016/j.1000-5404.202012225.
Min LIAO, Xuan LI, Liangjun ZHANG, et al. Artesunate reduces IL-6 production in primary mouse hepatocytes induced by conjugated bile acids through inhibiting p-p65 signaling pathway[J]. Journal of Third Military Medical University, 2021, 43(12): 1133-1139. DOI： 10.16016/j.1000-5404.202012225.
摘要
目的
2
探讨青蒿琥酯(Artesunate
AS)对结合型胆汁酸诱导的小鼠原代肝细胞IL-6表达水平的影响及机制。
方法
2
体外培养小鼠原代肝细胞，并用25 μmol/L的结合型胆汁酸处理，CCK-8法检测青蒿琥酯对小鼠原代肝细胞的毒性影响，RT-PCR法检测细胞因子IL-6的mRNA表达水平，蛋白印迹法检测肝细胞IL-6，p65
p-p65的水平。
结果
2
25 μmol/L结合型胆汁酸处理小鼠原代肝细胞能够诱导小鼠原代肝细胞IL-6的mRNA和蛋白质表达；青蒿琥酯减轻了TCA诱导的p65磷酸化和IL-6的蛋白水平；进一步研究发现青蒿琥酯是通过抑制p-p65(phosphorylated-p65)信号通路减轻小鼠原代肝细胞IL-6的表达。
结论
2
青蒿琥酯通过抑制p-p65信号通路减轻结合型胆汁酸诱导的原代小鼠肝细胞IL-6的产生。
Abstract
Objective
2
To investigate the effect and underlying mechanism of artesunate (AS) on the expression of interleukin-6 (IL-6) in mouse primary hepatocytes induced by conjugate bile acids.
Methods
2
Mouse hepatocytes were isolated and primarily cultured
and then treated with 25 μmol/L conjugated bile acids. CCK-8 assay was used to determine the toxic effects of AS on the liver cells. The mRNA level of IL-6 in the cells was measured by RT-qPCR
and the protein levels of IL-6
p-65 and phosphorylated-p65 (p-p65) were determined by Western blotting.
Results
2
Conjugated bile acids of 25 μmol/L significantly promoted the expression of IL-6 at mRNA and protein levels in mouse primary hepatocytes
while
AS reduced the taurocholic acid (TCA)-induced phosphorylation of p65 and IL-6 level. Further studies revealed that AS suppressed the IL-6 expression through inhibiting p-p65 signaling pathway in mouse primary hepatocytes.
Conclusion
2
AS reduces IL-6 expression in mouse primary hepatocytes induced by conjugate bile acids
via
inhibiting the p-p65 signaling pathway.
关键词
Keywords
references
岑彦艳, 赵祷博, 李攀, 等. 青蒿琥酯的药代动力学以及相关药理作用研究进展[J]. 中国中药杂志, 2018, 43(19): 3970-3978. DOI: 10.19540/j.cnki.cjcmm.20180726.010.
CEN Y Y, ZAO Y B, LI P, et al . Research progress on pharmacokinetics and pharmacological activities of artesunate[J ] . China J Chin Materia Medica, 2018, 43(19): 3970-3978. DOI: 10.19540/j.cnki.cjcmm.20180726.010.
ROUSSEL C, CAUMES E, THELLIER M, et al . Artesunate to treat severe malaria in travellers: review of efficacy and safety and practical implications[J ] . J Travel Med. 2017, 24(2). DOI: 10.1093/jtm/taw093.
LIU Z, ZHANG J, LI S, et al . Artesunate inhibits renal ischemia reperfusion-stimulated lung inflammation in rats by activating HO-1 pathway[J ] . Inflammation, 2018, 41(1): 114-121. DOI: 10.1007/s10753-017-0669-3.
LIU Y, HUANG G, MO B, et al . Artesunate ameliorates lung fibrosis via inhibiting the Notch signaling pathway[J ] . Exp Ther Med, 2017, 14(1): 561-566. DOI: 10.3892/etm.2017.4573.
QIAN P, ZHANG YW, ZHOU Z H, et al . Artesunate enhances γδ T-cell-mediated antitumor activity through augmenting γδ T-cell function and reversing immune escape of HepG2 cells[J ] . Immuno- pharmacol Immunotoxicol, 2018, 40(2): 107-116. DOI: 10.1080/08923973.2017.1386212.
KONG Z, LIU R, CHENG Y. Artesunate alleviates liver fibrosis by regulating ferroptosis signaling pathway[J]. Biomed Pharmacother, 2019, 109: 2043-2053. DOI: 10.1016/j.biopha.2018.11.030.
CAO J, WANG W, LI Y, et al . Artesunate attenuates unilateral ureteral obstruction-induced renal fibrosis by regulating the expressions of bone morphogenetic protein-7 and uterine sensitization-associated gene-1 in rats[J ] . Int Urol Nephrol, 2016, 48(4): 619-629. DOI: 10.1007/s11255-016-1232-0.
SUN Z, MA Y, CHEN F, et al . Artesunate ameliorates high glucose-induced rat glomerular mesangial cell injury by suppressing the TLR4/NF-κB/NLRP3 inflammasome pathway[J ] . Chem Biol Interact, 2018, 293: 11-19. DOI: 10.1016/j.cbi.2018.07.011.
CHIANG J Y L, FERRELL J M. Bile acid metabolism in liver pathobiology[J]. Gene Expr, 2018, 18(2): 71-87. DOI: 10.3727/105221618x15156018385515.
TAYLOR S A, GREEN R M. Bile acids, microbiota and metabolism[J]. Hepatology, 2018, 68(4): 1229-1231. DOI: 10.1002/hep.30078.
ATTILI A F, ANGELICO M, CANTAFORA A, et al . Bile acid-induced liver toxicity: relation to the hydrophobic-hydrophilic balance of bile acids[J ] . Med Hypotheses, 1986, 19(1): 57-69. DOI: 10.1016/0306-9877(86)90137-4.
JIA W, XIE G, JIA W. Bile acid-microbiota crosstalk in gastrointestinal inflammation and carcinogenesis[J]. Nat Rev Gastroenterol Hepatol, 2018, 15(2): 111-128. DOI: 10.1038/nrgastro.2017.119.
LI M, CAI S Y, BOYER J L. Mechanisms of bile acid mediated inflammation in the liver[J]. Mol Aspects Med, 2017, 56: 45-53. DOI: 10.1016/j.mam.2017.06.001.
CAI S Y, BOYER J L. The role of inflammation in the mechanisms of bile acid-induced liver damage[J]. Dig Dis, 2017, 35(3): 232-234. DOI: 10.1159/000450916.
宋传旺. 中性粒细胞产生IL-6的研究概述[J]. 泸州医学院学报, 2002, 25(6): 535-538.
SONG C W. Overview of studies on the production of IL-6 by neutrophils[J]. J Luzhou Med Coll, 2002, 25(6): 535-538.
SCHMIDT-ARRAS D, ROSE-JOHN S. IL-6 pathway in the liver: From physiopathology to therapy[J]. J Hepatol, 2016, 64(6): 1403-1415. DOI: 10.1016/j.jhep.2016.02.004.
GEIER A, JAHN D, HERMANNS H M. Interleukin-6: the dark side of liver regeneration in chronic liver disease[J]. Hepatology, 2017, 66(2): 667-668. DOI: 10.1002/hep.29136.
HE G, KARIN M. NF-κB and STAT3-key players in liver inflammation and cancer[J]. Cell Res, 2011, 21(1): 159-168. DOI: 10.1038/cr.2010.183.
BEUERS U, TRAUNER M, JANSEN P, et al. New paradigms in the treatment of hepatic cholestasis: from UDCA to FXR, PXR and beyond[J]. J Hepatol, 2015, 62(1 suppl): S25-S37. DOI:10.1016/j.jhep.2015.02.023.
CAI S Y, BOYER J L. Studies on the mechanisms of bile acid initiated hepatic inflammation in cholestatic liver injury[J]. Inflamm Cell Signal. 2017, 4(2): e1561.
SCHMITZ M L, BAEUERLE P A. The p65 subunit is responsible for the strong transcription activating potential of NF-kappa B[J]. EMBO J, 1991, 10(12): 3805-3817. DOI: 10.1002/j.1460-2075.1991.tb04950.x.
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