摘要
目的:研究鸡骨草总黄酮碳苷(AME)对乙硫氨酸(DL-E)所致小鼠脂肪肝的影响,并探讨其作用机制。方法:ICR小鼠随机分为4组:对照组,DL-E造模组,AME组和AME+DL-E组,每组8只。用AME连续灌胃给予AME组和AME+DL-E组小鼠7d,另外两组给予溶剂对照(三蒸水),第7天灌胃给予DL-E组和AME+DL-E组250mg/kg DL-E造模,其他两组给予溶剂对照(0.2%CMC-Na)。造模1h后再次灌胃给予所有小鼠AME或溶剂对照(三蒸水),造模22h后收集血样和肝组织,采用生化法测定血清脂质和转氨酶水平,肝脏TG以及TC含量。采用实时定量PCR的方法测定肝脏中相关脂代谢基因水平。结果:AME可以显著减少小鼠肝脏脂肪空泡的数量和脂变的面积,降低TG和TC含量以及血清转氨酶水平。在脂质相关代谢基因的调控上,AME可以下调DL-E导致的固醇调节元件结合蛋白-1(Sterol regulatory element binding protein 1,SREBP-1)、脂肪酸合成酶(Fatty acid synthase,FAS)和乙酰辅酶A羧化酶(Acetyl-CoA carboxylase 1,ACC1)的高表达,并且AME可以逆转DL-E对过氧化物酶体增殖物活化受体α(Peroxisome proliferator activatived receptorα,PPARα)和肉碱棕榈酰转移酶1α(Carnitine palmitoyltransferase 1α,CPT-1α)的抑制作用。结论:AME对DL-E引起的小鼠肝脏脂肪蓄积具有保护作用,并且这种作用主要是通过减少脂质合成,促进脂质氧化代谢来实现的。
AIM： To study the effect of total flavonoid C-glycosides from Abrus mollis extract（AME） on lipid dysregulation induced by Ethi onine （DL-E）. METHODS： ICR mice were randomly assigned to four groups （n=8） ; Control, DL-E, AME and AME＋DL-E groups. Mice were gavaged with AME （200 mg/kg） for 7 days. At day 7, mice of DL-E and AME＋DL-E group were gavaged with DL-E （250 mg/kg）, other two groups were treated with vehicle con- trol （0.2% CMC-Na）. Serum and liver tissues were collected 22 h after administration of DL- E. The contents of hepatic lipids, serum lipids and ALT, AST levels were measured. The ex- pressions of key genes involved in lipid metabo- lism were also observed by real-time PCR. RE- SULTS：The results indicated that AME provided significant protection against fatty liver by inhib- iting the elevation of serum lipids, serum trans- aminase, reducing hepatic TG and TC accumula-tion, ameliorating the severity of pathological changes. Furthermore, AME significantly de- creased DL-E-induced SREBP-1, FAS and ACC1 high expressions, which resulting in the lipid homeostasis. The down-regulation of CPT-1α and PPARα that reflect fatty acid metabolism in- duced by DL-E were reversed by AME treat- ment. CONCLUSION： The results indicated AME has hepatoprotective effect on Ethionine- induced fatty liver in mice and the effect was mostly due to the regulation on lipid synthesis and fatty acid metabolism.
出处
《中国临床药理学与治疗学》
CAS
CSCD
2014年第1期1-7,共7页
Chinese Journal of Clinical Pharmacology and Therapeutics
基金
国家"十一五"重大新药创制科技重大专项(2009ZX09103-315)
国家"十二五"重大新药创制专项(2013ZX09301-303-003)
高等学校学科创新引智计划(111-2-07)
2011年度江苏省高等学校优秀科技创新团队(200707008)
国家自然科学基金(81172955)
