护肝布祖热颗粒对酒精诱导小鼠急性肝损伤的保护作用和作用机制

Protective effect and mechanism of Hugan Buzure Granules on alcohol-induced acute liver injury in mice

目的探讨护肝布祖热颗粒对酒精性小鼠急性肝损伤的保护作用以及对NF-κb p65,Bax, Bcl-2及p-IκBɑ蛋白表达水平的影响。方法将72只昆明小鼠随机分为6组,分别为:空白组,模型组,护肝布祖热颗粒低剂量治疗组(1.25 g·kg^(-1)),护肝布祖热颗粒中剂量治疗组(2.5 g·kg^(-1)),护肝布祖热颗粒高剂量治疗组(5.0 g·kg^(-1))和阳性药复方益肝灵组(0.2 g·kg^(-1)),每组12只。对每组小鼠灌胃给予适当浓度的治疗药物,对于空白组给与生理盐水灌胃处理,持续14 d,在第13天时,对除空白组以外的小鼠给予无水乙醇灌胃处理(12 mL·kg^(-1)),制备酒精性急性肝损伤模型。在第15天时将小鼠称重,对肝组织进行生化指标,肝脏系数以及病理学指标的检测,使用蛋白质免疫印迹法对小鼠肝组织中的NF-κB p65,Bax, Bcl-2及p-IκBɑ蛋白含量进行测定。结果研究表明,护肝布祖热颗粒可明显降低小鼠肝脏系数;抑制肝组织中的肝细胞病变,并且抑制肝组织中ALT和AST活性,MDA以及总胆红素的含量,升高SOD活力值;抑制肝组织中蛋白NF-кB p65,p-IκBɑ,Bax的蛋白表达水平,提升Bcl-2蛋白表达。结论护肝布祖热颗粒对酒精致小鼠急性肝损伤有保护作用,其作用机制可能与抑制炎症和抑制肝细胞凋亡,下调NF-кB p65,p-IκBɑ的蛋白表达以及促凋亡蛋白Bax的表达,上调抑凋亡蛋白Bcl-2的表达有关。

Objective to investigate the protective effect of huganbuzure Granule on acute liver injury induced by alcohol in mice and its effect on the expression of NFκB p65,Bax, Bcl-2 and p-IκB ɑ proteins.Methods 72 Kunming mice were randomly divided into 6 groups: blank group, model group, huganbuzure granule low dose treatment group(1.25 g·kg^(-1)),huganbuzure granule medium dose treatment group(2.5 g·kg^(-1)),huganbuzure granule high dose treatment group(5.0 g·kg^(-1)) and positive drug compound Yiganling group(0.2 g·kg^(-1)),with 12 mice in each group.The mice in each group were given appropriate concentration of therapeutic drugs by gavage.The mice in the blank group were given normal saline by gavage for 14 days.On the 13 th day, the mice except the blank group were given anhydrous ethanol by gavage(12 mL·kg^(-1)) to prepare the alcoholic acute liver injury model.On the 15 th day, the serum and liver tissues of mice were collected for biochemical indexes, liver coefficient and pathological indexes.The protein contents of NFκB p65,Bax, Bcl-2 and p-IκB ɑ in liver tissues of mice were determined by Western blotting.Results The results show that huganbuzure granule can significantly reduce the liver coefficient of mice, inhibit the liver pathological changes, inhibit the activities of ALT and AST,the content of MDA and total bilirubin in liver tissue, increase the activity of SOD,inhibit the protein expression levels of NF-кB p65,p-IκB ɑ and Bax in liver tissue, and increase the protein expression level of Bcl-2.Conclusion Hugan Buzuere Granules had protective effects on acute liver injury in wine impaired mice.The mechanism of the protective effects might be related to inhibition of inflammation, inhibition of hepatocyte apoptosis, down-regulation of NFκB p65,p-IκB ɑ alpha protein expression, up-regulation of pro-apoptotic protein Bax and anti-apoptotic protein Bcl-2 expression.