甘草酸对大鼠肝纤维化过程中肝组织基因表达的影响

Effects of glycyrrhizin on genes expression during the process of liver fibrosis

目的 研究甘草酸抗肝纤维化作用的分子机制。方法 建立四氯化碳诱导肝纤维化和甘草酸治疗大鼠模型 ;选取正常组、造模组、治疗组大鼠肝脏各 1只进行cDNA微阵列研究 ;从cDNA微阵列结果中选取一个在造模大鼠肝脏中表达明显异常、但经甘草酸治疗后表达正常的基因(smurf2 ) ,用半定量RT PCR检测此基因在不同实验阶段 (第 1、2、4、8周 ) 3组大鼠中的表达变化。结果 通过cDNA微阵列发现smurf2、PTAFR、CYP2D6、FGG等多种与炎症、代谢有关的基因在造模大鼠肝脏中表达上调 ,甘草酸治疗后恢复正常表达。通过半定量RT PCR研究发现 ,经四氯化碳处理第 1周时smurf2在 3组大鼠肝脏中表达无异常变化 ,第 2周时在造模和治疗组中表达均下调 ,第 4周时在造模组中表达上调、治疗组中表达下调 ,第 8周时在造模组表达下调 ,治疗组上调。结论 调控smurf2基因转录水平可能是甘草酸抗肝纤维化作用的分子机制之一。

Objective To investigate the effects of glycyrrhizin on genes expression during the process of rat liver fibrosis. Methods Rat models of liver fibrosis were obtained by subcutaneous injections of CCl 4, another group were treated with both CCl 4 and glycyrrhizin. A control rat, a CCl 4 induced liver fibrosis rat and a glycyrrhizin treated rat were chosen to undergo cDNA microarray respectively. According to the results of cDNA microarray, a gene (smurf2) abnormally expressed in the liver fibrosis rat and expressed normally in the treated group was chosen to study its changes at different stages of experimental liver fibrosis by semi-quantitative RT-PCR. Results Many genes including smurf2, PTAFR, CYP2D6, FGG associated with inflammation and metabolism were identified increased expression in the CCl 4 treated group and normal expression in the glycyrrhizin group by cDNA microarray. Semi-quantitative RT-PCR showed after 1 week there were no differences of smurf2 gene expression levels among the three groups, after 2 weeks smurf2 gene expression levels decreased both in the CCl 4 group and glycyrrhizin group, after 4 weeks smurf2 gene expression levels increased in the CCl 4 group but decreased in glycyrrhizin group, after 8 weeks smurf2 gene expression levels decreased again in the CCl 4 group but increasd to the normal level in the glycyrrhizin group. Conclusion By cDNA microarray, we found the effects on the changes of smurf2 gene expression may contribute to the anti-fibrosis molecular mechanism of glycyrrhizin.