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目的:研究NF-κB及其抑制因子(IκB)在非酒精性脂肪性肝炎(NASH)发生中的作用,观察山楂叶总黄酮(TFHL)对其的影响,探讨TFHL防治NASH的作用机制。方法:以高脂饮食喂养SD大鼠12周建立大鼠NASH模型,同时分别以250、125mg.kg-1.d-1的TFHL和195.4mg.kg-1.d-1的易善复进行干预,观察大鼠肝组织的病理改变,血清MDA、SOD、TNF-α水平,RT-PCR和免疫组化法检测NF-κB及其抑制物IκB基因m RNA和蛋白在肝组织中的表达。结果:高脂脂饮食诱导NASH大鼠肝组织出现重度脂肪变、不同程度的炎细胞浸润及坏死灶,血清MDA、TNF-α含量较正常大鼠显著增高,SOD活性下降,肝组织NF-κB p65、IκBα基因的mRNA和蛋白表达明显增强;同时肝组织NF-κB p65、IκBα蛋白表达与血清TNF-α和MDA含量呈明显正相关,与血清SOD活性呈明显负相关;TFHL和易善复能显著改善NASH大鼠的炎症程度,能提高大鼠的血清SOD水平,降低MDA和TNF-α的含量,降低肝组织NF-κB p65、IκBα基因的mRNA和蛋白的表达。结论:TFHL能减少NASH大鼠脂质过氧化反应,减少细胞因子对肝细胞的损伤,调节组织NF-κB p65、IκBα基因的mRNA和蛋白的表达,这可能是其防治NASH发展的重要机制。
Objective: To investigate the effect of NF-κB and its inhibitory factor (IκB) on the development of non-alcoholic steatohepatitis (NASH) and observe the effects of hawthorn leaf flavonoids (TFHL) on it. Methods: The rats were fed with a high-fat diet for 12 weeks to establish the model of NASH. At the same time, TFHL of 250,125 mg.kg-1.d-1 and Ephrenol complex of 195.4 mg.kg-1.d-1 The levels of MDA, SOD and TNF-α were detected by RT-PCR and immunohistochemistry. The expressions of NF-κB and its inhibitor IκB mRNA and protein were detected by RT-PCR and immunohistochemistry. Results: The rats with NASH induced by high-fat diet had severe steatosis and inflammatory cell infiltration and necrosis in the liver tissue. The levels of serum MDA and TNF-α were significantly higher in NASH rats than in normal rats, while the activity of SOD was decreased. The levels of NF-κB p65 mRNA and protein expression of IκBα gene was significantly increased. At the same time, the expression of NF-κB p65 and IκBα in liver tissue was positively correlated with serum TNF-α and MDA content, but negatively correlated with serum SOD activity. TFHL, Can significantly improve the degree of inflammation in NASH rats, increase the level of serum SOD, decrease the content of MDA and TNF-α, and decrease the mRNA and protein expression of NF-κB p65 and IκBα in liver tissues. CONCLUSION: TFHL can reduce the lipid peroxidation, decrease the cytotoxicity of hepatocytes and regulate the mRNA and protein expression of NF-κB p65 and IκBα in NASH rats, which may be one of the important mechanisms for the prevention and treatment of NASH.