蛋白激酶CK2α在大鼠肝纤维化病理过程中的表达变化

The expression of protein kinase CK2α in rat hepatic fibrogenesis process

目的：观察蛋白激酶casein kinaseⅡα（CK2α）在大鼠肝纤维化病理过程中的表达变化，以及10-甲氨基-8-硫代苦参碱（M ASM ）抗肝纤维化治疗对CK2α表达的影响。方法采用二甲基亚硝胺（DM N ）和胆管结扎术（BDL ）的方法建立大鼠肝纤维化模型，造模后灌胃给予M ASM （50 mg／kg ）和生理盐水进行治疗。肝组织切片分别采用苏木精-伊红染色进行病理分析，用天狼星红和M asson胶原染色判定肝纤维化程度，免疫组织化学法观察纤维化肝组织中CK2α和α-平滑肌肌动蛋白（α-SM A ）的表达变化。结果与对照组相比，DM N及BDL诱导的肝纤维化组织中CK2α的表达水平均显著上调；注射DM N造模1～4周，随着造模时间的延长，α-SM A表达逐渐增加，CK2α的表达水平相应显著上调；与模型组相比，M ASM 药物治疗组大鼠肝纤维化程度明显缓解，同时CK2α的表达水平显著下调。结论蛋白激酶CK2α的表达水平与肝纤维化的形成呈正相关关系；苦参碱衍生物M ASM抗肝纤维化作用伴随下调CK2α的表达水平，提示CK2α是一个肝纤维化治疗的潜在靶点。

Objective To observe the dynamic characteristics of protein kinase ,casein kinase II α （CK2α） ,expression during hepatic fibrogenesis in rats ;and the effects of a matrine derivative ,13-methylamino-18-thione-matrine （M ASM ） ,on CK2αexpression when it is used for anti-fibrotic treatment .Methods Hepatic fibrosis model was established in SD rats by dimethylnitrosamine （DMN） injection or by bile duct ligation （BDL） .The established fibrotic rats were given 50 mg/kg MASM or saline as a control by gavage for three weeks .The level of hepatic fibrosis was evaluated by histopathology examina-tion using hematoxylin-eosin staining ,and using the sirius red and Masson＆#39;s trichrome staining for collagen determination in fi-brosis .The expressions of CK2αandα-smooth muscle actin （α-SMA） in hepatic tissues were detected by immunohistochemis-ry .Results CK2α is mainly expressed in the stellate cells of fibrotic livers induced by DM N or BDL comparing the control group .Along with the development of hepatic fibrosis as evidenced by α-SMA expression ,increased CK2α-positive cells in liver were detected while injecting DMN in the rats for one to four weeks .MASM treatment significantly inhibited the hepatic fibro-sis and suppressed the expression of CK2αcomparing the model group .Conclusion The expression level of CK2α,and hepatic fibrosis formation are positively correlated .The matrine derivative ,MASM ,can significantly inhibit hepatic fibrosis and sup-press the CK2αexpression .These results suggest CK2αmay be a potential target for hepatic fibrosis therapy .