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

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。

To observe the effects of emodin（ Emo） on acute fatty liver in mice induced by DL-ethionine（ DLEth） 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-Co A 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.