CAJ | 학술논문

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。
목적：관찰단백격매casein kinaseⅡα（CK2α）재대서간섬유화병리과정중적표체변화，이급10-갑안기-8-류대고삼감（M ASM ）항간섬유화치료대CK2α표체적영향。방법채용이갑기아초알（DM N ）화담관결찰술（BDL ）적방법건립대서간섬유화모형，조모후관위급여M ASM （50 mg／kg ）화생리염수진행치료。간조직절편분별채용소목정-이홍염색진행병리분석，용천랑성홍화M asson효원염색판정간섬유화정도，면역조직화학법관찰섬유화간조직중CK2α화α-평활기기동단백（α-SM A ）적표체변화。결과여대조조상비，DM N급BDL유도적간섬유화조직중CK2α적표체수평균현저상조；주사DM N조모1～4주，수착조모시간적연장，α-SM A표체축점증가，CK2α적표체수평상응현저상조；여모형조상비，M ASM 약물치료조대서간섬유화정도명현완해，동시CK2α적표체수평현저하조。결론단백격매CK2α적표체수평여간섬유화적형성정정상관관계；고삼감연생물M ASM항간섬유화작용반수하조CK2α적표체수평，제시CK2α시일개간섬유화치료적잠재파점。
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'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 .