大黄素对小鼠急性脂肪肝的改善作用
Improvement of emodin on acute fatty liver in mice
-
摘要: 探讨大黄素对DL-乙硫氨酸和四环素分别诱导的小鼠急性脂肪肝的改善作用及机制。雄性ICR小鼠连续给予大黄素或阳性对照药熊去氧胆酸共7 d，第7天给予DL-乙硫氨酸，建立DL-乙硫氨酸脂肪肝模型。雄性ICR小鼠连续给予大黄素或阳性对照药东宝甘泰、鸡骨草总黄酮碳苷共7 d，在给药第4天起每天给予四环素，建立四环素脂肪肝模型。HE染色观察肝脏病理改变；检测血清中丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、三酰甘油(TG)和肝TG、总胆固醇(TC)水平。Western blot测定肝磷酸化腺苷酸活化蛋白激酶(p-AMPK)、磷酸化乙酰辅酶A羧化酶(p-ACC)、SREBP1和脂肪酸合酶(FAS)蛋白的表达。RT-PCR测定肝脏脂肪酸转位酶(CD36)、过氧化物酶体增殖物激活受体α(PPARα)和微粒体三酰甘油转运蛋白(MTTP)基因的表达。与模型组相比，大黄素能改善DL-乙硫氨酸和四环素引起的肝细胞肿大及小泡型肝脂肪变性；显著降低血清TG、AST、ALT和肝脏TG、TC的水平；抑制DL-乙硫氨酸引起的肝脏脂肪酸合成相关蛋白表达的增加；减少肝脏脂肪酸的摄取、增加脂肪酸的氧化及分泌。结果表明，大黄素对DL-乙硫氨酸和四环素引起的脂肪肝具有改善作用。Abstract: To observe the effects of emodin(Emo)on acute fatty liver in mice induced by DL-ethionine(DL-Eth)or tetracyclin(Tetra)and its potential mechanism, ICR mice of acute fatty liver model induced by DL-Eth were orally administered with Emo or positive control, ursodeoxycholic acid(UDCA)for 7 days. On day 7, except that the control and Emo groups were treated with vehicle control, animals were orally administered with DL-Eth to induce acute fatty liver model. ICR mice of acute fatty liver model induced by Tetra were orally administered with Emo or positive control, Dong Bao Gan Tai (DB)or total flavonoid C-glycosides from Abrus mollis extract(AME)for 7 days. From day 4, except that the control group was treated with vehicle control, animals were injected with Tetra intraperitoneally for 4 days to induce acute fatty liver model. Liver histopathological analyses were determined by HE staining. Serum aspartate transaminase(AST), alanine transaminase(ALT), serum triglyceride(TG), hepatic TG and hepatic total cholesteol(TC)were detected. The expression of phosphorylated AMP-activated kinase(p-AMPK), phosphorylated acetyl-CoA carboxylase(p-ACC), SREBP1 and fatty acid synthase(FAS)were determined by Western blot. The expression of fatty acid translocase(CD36), peroxisome proliferator activated receptor alpha(PPARα)and microsomal triglyceride transfer protein(MTTP)in liver were determined by RT-PCR. Compared with model groups, Emo could improve hepatocyte swelling and hepatic steatosis induced by DL-Eth or Tetra. Serum AST, ALT, serum TG, hepatic TG and hepatic TC were decreased by Emo significantly. DL-Eth-induced increase of fatty acid synthetase-associated protein was down-regulated by Emo. Fatty acid uptake was down-regulated by Emo; fatty acid oxidation and secretion were increased by Emo. Emo might be effective in preventing acute fatty liver in mice induced by DL-Eth or Tetra.
-
Keywords:
- emodin /
- DL-ethionine /
- tetracyclinacute /
- fatty liver /
- protection
-
-
[1] Hardwick JP,Osei-Hyiaman D,Wiland H,et al.PPAR/RXR regulation of fatty acid metabolism and fatty acid omega-hydroxylase(CYP4)isozymes:implications for prevention of lipotoxicity in fatty liver disease[J].PPAR Res,2009,2009:952734. [2] Portincasa P, Grattagliano I, Palmieri VO, et al. Nonalcoholic steatohepatitis:recent advances from experimental models to clinical management[J].Clin Biochem,2005,38(3):203-217. [3] Xue J,Ding W,Liu Y.Anti-diabetic effects of emodin involved in the activation of PPARgamma on high-fat diet-fed and low dose of streptozotocin-induced diabetic mice[J].Fitoterapia,2010,81(3):173-177. [4] Song P,Kim JH,Ghim J,et al.Emodin regulates glucose utilization by activating AMP-activated protein kinase[J].J Biol Chem,2013,288(8):5732-5742. [5] Heo SK, Yun HJ, Park WH, et al. Emodin inhibits TNF-alpha-induced human aortic smooth-muscle cell proliferation via caspase-and mitochondrial-dependent apoptosis[J].J Cell Biochem,2008,105(1):70-80. [6] Wang CH, Gao ZQ, Ye B, et al. Effect of emodin on pancreatic fibrosis in rats[J].World J Gastroenterol,2007,13(3):378-382. [7] Liu WH,Qi Y,Jia D.Research progress on experimental models of non-alcoholic fatty liver disease[J].Shanghai J Tradit Chin Med(上海中医药杂志),2015,49(3):95-97. [8] Yoshizawa F,Mochizuki S,Doi M,et al.Ethionine-induced ATP depletion represses mTOR signaling in the absence of increases in AMP-activated protein kinase activity in the rat liver[J].Biosci Biotechnol Biochem,2009,73(9):1984-1988. [9] Yu HY,Wang BL,Zhao J,et al.Protective effect of bicyclol on tetracycline-induced fatty liver in mice[J].Toxicology,2009,261(3):112-118. [10] Choi YJ, Lee CH, Lee KY, et al. Increased hepatic Fatty Acid uptake and esterification contribute to tetracycline-induced steatosis in mice[J].Toxicol Sci,2015,145(2):273-282. [11] BénichouC.Criteria of drug-induced liver disorders.Report of an international consensus meeting[J].J Hepatol,1990,11(2):272-276. [12] Kohjima M,Enjoji M,Higuchi N,et al.Re-evaluation of fatty acid metabolism-related gene expression in nonalcoholic fatty liver disease[J].Int J Mol Med,2007,20(3):351-358. [13] Raghow R,Yellaturu C,Deng X,et al.SREBPs:the crossroads of physiological and pathological lipid homeostasis[J].Trends Endocrinol Metab,2008,19(2):65-73. [14] Browning JD,Horton JD.Molecular mediators of hepatic steatosis and liver injury[J].J Clin Invest,2004,114(2):147-152. [15] Li Y, Xu S, Mihaylova MM, et al. AMPK phosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and atherosclerosis in diet-induced insulin-resistant mice[J].Cell Metab,2011,13(4):376-388. -
期刊类型引用(4)
1. 宋永真，李雅静，张振凌，王胜超. 曼地亚红豆杉酒炙工艺及质量标准研究. 中医学报. 2024(05): 1068-1075 . 
百度学术
2. 剡槿熙，臧明伍，刘贺，徐晨晨，史宇璇，白京，赵燕，郝静怡，张亚茹. 二萜类化合物在肉类食品保鲜防腐中的应用研究进展. 食品科学. 2024(13): 282-291 . 百度学术
3. 王楠楠，蔡婷婷，童晔玲，刘霞，朱婉萍，江石平，赵桂芝. 基于NF-κB信号通路的HTRF法筛选红豆杉中抗气道炎症有效活性成分研究. 浙江中医杂志. 2023(08): 553-556 . 百度学术
4. 傅贵江. 杉木人工林抚育间伐对套种南方红豆杉的影响. 武夷科学. 2022(01): 39-43 . 百度学术
其他类型引用(5)
计量
- 文章访问数:
- HTML全文浏览量: 0
- PDF下载量:
- 被引次数: 9
下载:
