12-异甘草酸镁抗炎作用机制研究-钟才云

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Immunity.2014;40(1):13-24
Drug Hepatotoxicity
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J Gastroenterol Hepatol. 2011;26 Suppl 1:173-9
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Cell. 2010 ;140(6):883-99
Inflammation, Fibrosis, and Carcinogenesis
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Clin Cancer Res, 2013; 19(11); 2810–6
Reactive Oxygen and Liver Inflammation
Cell. 2010;140(6):935-50
Inhibitors of MAPKs
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Nat Rev Immunol. 2013;13(9):679-92
Inhibitors of NF-κB
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异甘草酸镁（甘美）
➢ 18α-甘草酸单一立体异构体镁盐 ➢ 一类新药 ➢ 临床应用于抗炎、保护肝脏 ➢ 抗炎作用机制尚待研究
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甘美抑制LPS诱导的炎性细胞因子水平(RAW264.7)
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甘美对炎症模型肝脏中细胞因子和NO的影响（小鼠）
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甘美抑制肝脏中PLA/AA介导的炎性介质（小鼠）
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蛋白表达水平； ➢ 与糖皮质激素相比，甘美对主要炎性反应信号通路、关键分子靶标及
炎性因子基因表达的调控作用相似，然作用强度相对较弱；
➢ 甘美具有明显降低细胞内ROS的作用。
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甘美抗炎作用模型
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Int J hepatolo. 2012(10): 1151-1159
Origin of Inflammation
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Cell. 2006 ;124(4):823-3 Gastroenterology. 2012;143:1158–1172
J Clin Invest. 2005; 115:2625–2632
MAPK and Inflammation
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Science. 2002; 298:1911
PLA/AA and Inflammation
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Production and Release of IL-1β
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Cell. 2010;140(6):935-50
Points of Inhibition by Anti-inflammatory Agents
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甘美抑制LPS诱导的NO、iNOS水平(RAW264.7)
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甘美抑制 LPS诱导的 cPLA2
(RAW264.7)
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甘美抑制花生四烯酸代谢酶水平（RAW264.7）
NaBaidu Nhomakorabeaural History of Chronic Liver Disease
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Nat Rev Immunol. 2014 ;14(3):181-94
NF-κB and Inflammation
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甘美抑制LPS诱导的NF-κB 和 MAPK活性（小鼠）
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结论
➢ 甘美剂量依赖性地抑制由炎症刺激诱导的PLA2/AA、NF-κB 和MAPK 关键炎性反应信号通路的活性；
➢ 甘美明显降低由炎症信号调控的炎性反应酶 （PLA2、COX-2、LOX、 iNOS）、脂质炎症介质（前列腺素、 血栓素、白三烯 ）、 细胞因子 （IL-1β、IL-6 、TNF-α） 、细胞趋化因子（IL-8）等炎性因子基因与
Alcoholic liver disease
Non alcoholic fatty liver disease
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Diabetes
Obesity and Liver Disease
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Int J Mol Sci. 2014 ;15(4):6184-223
Alcoholic Liver Disease
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J Gastroenterol Hepatol. 2013 ;28 Suppl 1:77-84
Viral Hepatitis
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甘美抑制花生四烯酸代谢脂质炎症介质（RAW264.7）
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甘美对NF-κB活性的抑制作用（RAW264.7）
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Hallmarks of Cancer: The Next Generation
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Cell. 2011 ;144(5):646-74
Role of Inflammation in Cancer
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Inflammation. 2012;35(2):560-5
Inhibitors of PLA2
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Expert Opin. Ther. Patents .2013; 23(3):333-344
Magnesium Isoglycyrrhizinate
甘美对MAPK活性的抑制作用（RAW264.7）
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甘美对细胞内ROS水平的抑制作用（RAW264.7）
PBS
PBS+LPS
MgIG 0.5+LPS
MgIG 1+LPS
DMSO
DMSO+LPS
DEX10-6+LPS
DEX10-5+LPS
Liver Fibrosis
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Nat Rev Immunol. 2014 ;14(3):181-94
Hallmarks of Cancer
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Cell. 2000 ;100(1):57-70
HYD10-4 +LPS
HYD10-3 +LPS
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免疫荧光
甘美对细胞内ROS水平的抑制作用（RAW264.7）
（流式细胞术）
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甘美对血清中细胞因子 水平的影响（小鼠）
异甘草酸镁抗炎作用机制研究
南京医科大学公共卫生学院 钟才云
Inflammation-associated Liver Diseases
Liver cancer
Viral infection HBV/HCV
Chemical liver injury
Drug hepatotoxicity
Liver fibrosis