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异甘草酸镁在环磷酰胺诱导的肝损伤模型中显示出肝脏保护作用。

Magnesium isoglycyrrhizinate shows hepatoprotective effects in a cyclophosphamide-induced model of hepatic injury.

作者信息

Jiang Wenjiao, Liu Jingyan, Li Peijin, Lu Qianfeng, Pei Xue, Sun Yilin, Wang Guangji, Hao Kun

机构信息

Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China.

Department of Physiology and Pharmacology, China Pharmaceutical University, Nanjing 210009, China.

出版信息

Oncotarget. 2017 May 16;8(20):33252-33264. doi: 10.18632/oncotarget.16629.

Abstract

The purpose of the current study was to investigate the effect of Magnesium Isoglycyrrhizinate (GM) on cyclophosphamide (CP)-induced hepatic injury in vivo and in vitro. The results demonstrated that GM exerted a protective effect on CP-induced acute liver injury, as evidenced by the alleviations of hepatic pathological damage and serum transaminase activities. Meantime, GM attenuated serum and HepG2 cell supernatant levels of TNF-α, IL-6, IL-1β, SOD and MDA. Western blot results presented that GM down-regulated the expressions of the microtubule associated protein 1A/1B-light chain 3 (LC3), Lysosome associated membrane protein-1 (LAMP-1), p-phosphatidylinositol 3-kinase (PI3K), p-protein Kinase B(Akt), p-mechanistic target of rapamycin(mTOR), p-ribosomal protein S6 kinase 70 kDa (p70S6K), p-4E binding protein 1(4EBP1), p- inhibitor of NF-κB(IκB)α and p-nuclear factor kappa B(NF-κB)p65 in CP-stimulated hepatic tissue and HepG2 cells. Taken together, our results suggested that GM showed beneficial effect on CP-induced liver injury through NF-κB-mediated inflammation and PI3K/Akt/mTOR/p70S6K/4EBP1 axis-mediated autophagy in vivo and in vitro.

摘要

本研究的目的是探讨异甘草酸镁(GM)对环磷酰胺(CP)诱导的体内外肝损伤的影响。结果表明,GM对CP诱导的急性肝损伤具有保护作用,肝病理损伤减轻和血清转氨酶活性降低证明了这一点。同时,GM降低了血清和HepG2细胞上清液中TNF-α、IL-6、IL-1β、SOD和MDA的水平。蛋白质免疫印迹结果显示,GM下调了CP刺激的肝组织和HepG2细胞中微管相关蛋白1A/1B轻链3(LC3)、溶酶体相关膜蛋白-1(LAMP-1)、磷酸化磷脂酰肌醇3激酶(PI3K)、磷酸化蛋白激酶B(Akt)、磷酸化雷帕霉素靶蛋白(mTOR)、磷酸化核糖体蛋白S6激酶70 kDa(p70S6K)、磷酸化4E结合蛋白1(4EBP1)、磷酸化核因子κB抑制蛋白(IκB)α和磷酸化核因子κB(NF-κB)p65的表达。综上所述,我们的结果表明,GM在体内外通过NF-κB介导的炎症和PI3K/Akt/mTOR/p70S6K/4EBP1轴介导的自噬对CP诱导的肝损伤显示出有益作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fdfb/5464865/e7ad6d24d2a0/oncotarget-08-33252-g001.jpg

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