甘草酸对四氯化碳诱导大鼠肝纤维化肝组织p53蛋白表达的影响

Effects of glycyrrhizic acid on the expression of p53 protein in rat liver fibrosis induced by CCl_4

目的探讨甘草酸对四氯化碳诱导大鼠肝纤维化肝组织p53蛋白表达的影响。方法45只雄性SD大鼠随机均分为对照组、肝纤维化组和甘草酸干预组3组,每组各15只。肝纤维化组和甘草酸干预组构建四氯化碳诱导大鼠肝纤维化模型,对照组大鼠注射等量的橄榄油。甘草酸干预组大鼠以0.2%甘草酸溶液予腹腔注射,3 ml/只,3次/周;对照组大鼠予等量双蒸水替代。3组于实验第1、4、8周各处死5只大鼠,取肝组织行HE染色检测纤维化情况,采用免疫组织化学和Western印迹定量分析检测p53蛋白在大鼠肝组织内的表达情况。采用单因素方差分析比较各组大鼠实验第1、4、8周p53蛋白表达量差异,进一步组间两两比较采用LSD-t检验。结果实验第1周,3组大鼠肝组织p53蛋白表达量差异无统计学意义;实验第4、8周,肝纤维化组大鼠肝组织中p53蛋白表达量均较对照组大鼠升高,而甘草酸干预组大鼠肝组织中p53蛋白表达量均较肝纤维化组大鼠降低,且差异均有统计学意义(实验第4周:t值分别为2.39、2.74;实验第8周:t值分别为1.58、7.79;P值均为0.000)。结论甘草酸可减缓肝纤维化进程,其分子机制可能与p53蛋白的表达下调有关。

Objective To explore the effects of glycyrrhizic acid （GA）on the expression of p53 protein in different periods of rat liver fibrosis induced by CCl4 .Methods Forty-five male Sprague-Dawley rats were randomly divided into three groups,the control group,the liver fibrosis group,and the GA treatment group.The rats in liver fibrosis group and GA treatment group were injected with CCl4 to build liver fibrosis models,and the rats in control group were injected with the equal olive oil.The rats in GA treatment group were treated with 0.2%GA solution by intraperitoneal injection,3 ml per rat,three times a week.The rats in control group were treated with the equal double distilled water.After 1 ,4,8 weeks of treatment,5 rats in each group were killed,pathologic changes in the liver were detected by hematoxylin and eosin staining,the expressions of p53 protein in different periods of liver fibrosis were evaluated by immunohistochemical staining and Western blot analysis.The expression difference of p53 protein in different groups and different periods was compared with single factor analysis of variance.The difference of each two groups was analyzed with LSD-t test.Results After 1 week,there was no difference of p53 protein expression among the three groups.After 4,8 weeks,p53 protein expression in liver fibrosis group was higher than that in control group,and p53 protein expression in GA treatment group was lower than that in liver fibrosis group,and the differences were statistically significant （after 4 weeks：t=2.39,2.74;after 8 weeks：t=1.58,7.79;all P=0.000）.Conclusion GA can retard the progress of liver fibrosis in rats and down-regulation of p53 may contribute to GA effects.