甘草甜素对肝硬化动物模型肝脏内NF一kB结合活性的抑制作用

Inhibitory effect of glycyrrhizin on NF-κB binding activity in CCI_4 plus ethanol induced liver cirrhosis in rats

从分子水平探讨强力宁生物活性的发生机理。方法大鼠随机分为正常对照组、模型对照组、强力宁组，后两组给子四氯化碳（ＣＣ１４）和乙醇造模处理以诱导慢性肝损伤，强力宁组在造模处理同时予强力宁治疗。各组大鼠在ＣＣ１４等处理后第９周处死，收集血清和肝脏标本，测定血清ＡＬＴ活性并进行组织学观察。部分肝组织提取细胞核蛋白进行凝胶迟滞实验以观察ＮＦ－ＫＢ活性。结果ＣＣ１４等处理后第９周模型对照组血清ＡＬＴ水平显著高于强力宁组。模型大鼠肝脏脂肪变性和纤维化程度较强力宁治疗组更为严重。模型对照组肝脏内ＮＦ－ＸＢ活性较正常对照组显著增加，而强力宁组大鼠肝脏内ＮＦ－ｋＢ结合活性与正常组相接近。结论强力宁能够抑制ＣＣ１４联会乙醇诱导的慢性肝损伤大鼠肝脏内ＮＦ－ｋＢ的结合活性的增加，可能是强力宁具有保护肝毒素性肝损伤和纤维化作用的分子机制之一。

Objective To investigate the effects of Pot6nlnd on nuclear factor-kB(OF-kB) bindingactivity in the livers of animals models with liver cirrhosis, and to delineate the molecular mechanism ofthe bioactivities of Potenlini. Methods Male SD rats were randomly allocated into a normal control gToup,a model control group, and a Potenlini group. Rats in the latter two groups were treated with CC14k andEthanol solution in order to induce chronic liver injury. Rats in Potedrii group were given Potenlinitreatment at the same time. All rats were killed at thd gth week after CCk admndStration. Serum andliver specimens were collected, serum ALT activities and histological findings were assessed. Nuclearextracts from liver tissues were prepared and afl retardation assayS were performed for the evaluation ofNF-GB activity. Results (l)Serum ALT levels were significantly reduced in ratS treated with Poteulinicompared with those in rats of the model control group, which had dramatically increase ALT levels. (2)Histologically, liver steatosis and fibrosis were severe in the rats of the model group, but weresignificantly improved in rats of the Pot6niini group. (3)OF-kB binding activity was markedly increase inthe liver speimens taken from the rats of the model control group in comparison with the binding ofnormal livers, but the binding levels were nearly normal in the livers of the Poteulini gToup. ConclusionPotenlini can inhibit the OF-kB binding activity in CC14 and ethanol induced chronic liver injury, andthat may partially be the mechanism by which Potenlini protects liver from hepatotoxin-induced liverinjury and cirrhosis.