蛋白激酶CK2α在大鼠肝纤维化病理过程中的表达变化
投稿时间:2015-06-10  修订日期:2015-10-11  点此下载全文
引用本文:王珂琪,许维恒,丁力,张俊平.蛋白激酶CK2α在大鼠肝纤维化病理过程中的表达变化[J].药学实践杂志,2015,33(6):518~521,575
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作者单位E-mail
王珂琪 第二军医大学药学院生化药学教研室, 上海 200433  
许维恒 第二军医大学药学院生化药学教研室, 上海 200433  
丁力 第二军医大学药学院生化药学教研室, 上海 200433  
张俊平 第二军医大学药学院生化药学教研室, 上海 200433 jpzhang08@163.com 
基金项目:国家自然科学基金项目(No.81170404)
中文摘要: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(MASM)抗肝纤维化治疗对CK2α表达的影响。 方法 采用二甲基亚硝胺(DMN)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MASM(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Masson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-SMA)的表达变化。 结果 与对照组相比,DMN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DMN造模1~4周,随着造模时间的延长,α-SMA表达逐渐增加,CK2α的表达水平相应显著上调;与模型组相比,MASM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MASM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。
中文关键词:蛋白激酶CK2α  肝纤维化  苦参碱衍生物  靶点
 
The expression of protein kinase CK2α in rat hepatic fibrogenesis process
Abstract: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 (MASM), on CK2α expression 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 examination using hematoxylin-eosin staining, and using the sirius red and Masson's trichrome staining for collagen determination in fibrosis. The expressions of CK2α and α-smooth muscle actin (α-SMA) in hepatic tissues were detected by immunohistochemisry. Results CK2α is mainly expressed in the stellate cells of fibrotic livers induced by DMN 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 fibrosis and suppressed the expression of CK2α comparing 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 suppress the CK2α expression. These Results suggest CK2α may be a potential target for hepatic fibrosis therapy.
keywords:casein kinase II α(CK2α)  hepatic fibrosis  matrine derivative  target
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