豹皮樟总黄酮对非酒精性脂肪性肝炎治疗作用及部分机制

Therapeutic effects of Total Flavonoids of Litsea Coreana leve on nonalcoholic steatohepatitis and its partly mechanisms of action

目的研究豹皮樟总黄酮对大鼠非酒精性脂肪性肝炎(NASH)治疗作用,并初步探讨Toll样受体4(TLR4)在治疗中的作用。方法将SD大鼠随机分为5组:正常组、模型组及TFLC组(100、200、400 mg.kg-1)。除正常组外,其余各组每天给予脂肪乳剂灌胃连续10周,制备NASH模型。治疗组于造模第6周开始灌胃给予相应剂量的药物。实验10周后,检测血清ALT、AST、TC、TG、TNF-α及肝脏TC、TG含量、TLR4 mRNA和蛋白表达、NF-κB核蛋白表达,并行病理组织学检查。结果模型组大鼠血清ALT、AST、TG、TC、TNF-α水平及肝脏TC、TG含量明显升高,病理组织学检查显示模型组大鼠发生明显的肝细胞脂肪变性、炎症和坏死。TFLC能降低模型大鼠血清ALT、AST、TG、TC、TNF-α水平及肝脏TC、TG含量,病理组织学检查显示TFLC明显改善大鼠肝细胞脂肪变性及炎症程度减轻。进一步研究发现TFLC能明显抑制TLR4 mRNA和蛋白表达、NF-κB核蛋白水平。结论 TFLC对NASH有较好的治疗作用,且与抑制TLR4介导的细胞信号转导通路有关。

Aim To study the therapeutic effect of total flavonoids of Litsea Coreana leve（TFLC） on nonalcoholic steatohepatitis（NASH） in rats and evaluate the role of Toll-like receptor 4（TLR4）signaling pathways.Methods The NASH model was induced by high fat emulsion in rats for 10 weeks,TFLC（100,200,400 mg·kg-1） was administered via gavage daily after fed with high fat emulsion from the 6th week.The serum was taken for lanine aminotransferase（ALT）,aspartate aminotransferase（AST）,TG,TC and TNF-α measuring.Liver tissues were taken for pathological examination and TG,TC dectection.TLR4 mRNA was examined by RT-PCR,while TLR4 and NF-κB protein was measured by Western blot.Results In the model group,serum ALT,AST,TG,TC and TNF-α levels were significantly increased and TG,TC level in liver were elevated,and high degree of steatosis with inflammation and necrosis were observed.TFLC improved liver histology with reduced serum levels of ALT and AST,as well as decreased the over accumulaed lipids in serum and liver.Furthermore,hepatic TLR4 mRNA,nuclear NF-κB protein expression and serum tumor necrosis factor α（TNF-α） were reduced by TFLC.Conclusions TFLC exerts therapeutic effects against nonalcoholic steatohepatitis,and these effects may be associated with TLR4 dependent signaling pathways.