蛋白激酶CK2α在大鼠肝纤维化病理过程中的表达变化

王珂琪; 许维恒; 丁力; 张俊平

doi:10.3969/j.issn.1006-0111.2015.06.010

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蛋白激酶CK2α在大鼠肝纤维化病理过程中的表达变化

王珂琪, 许维恒, 丁力, 张俊平

文章导航 > 药学实践与服务 > 2015 > 33(6): 518-521,575

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]. 药学实践与服务, 2015, 33(6): 518-521,575. doi: 10.3969/j.issn.1006-0111.2015.06.010

引用本文:

WANG Keqi, Xu Weiheng, Ding Li, ZHANG Junping. The expression of protein kinase CK2α in rat hepatic fibrogenesis process[J]. Journal of Pharmaceutical Practice and Service, 2015, 33(6): 518-521,575. doi: 10.3969/j.issn.1006-0111.2015.06.010

Citation:

WANG Keqi, Xu Weiheng, Ding Li, ZHANG Junping. The expression of protein kinase CK2α in rat hepatic fibrogenesis process[J]. Journal of Pharmaceutical Practice and Service, 2015, 33(6): 518-521,575. doi: 10.3969/j.issn.1006-0111.2015.06.010

蛋白激酶CK2α在大鼠肝纤维化病理过程中的表达变化

doi: 10.3969/j.issn.1006-0111.2015.06.010

第二军医大学药学院生化药学教研室, 上海 200433

基金项目: 国家自然科学基金项目(No.81170404)

The expression of protein kinase CK2α in rat hepatic fibrogenesis process

Department of Biochemic Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China

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。
- 蛋白激酶CK2α /
- 肝纤维化 /
- 苦参碱衍生物 /
- 靶点
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.
- casein kinase II α(CK2α) /
- hepatic fibrosis /
- matrine derivative /
- target

[1]	Lee UE, Friedman SL. Mechanisms of hepatic fibrogenesis[J]. Best Pract Res Clin Gastroenterol, 2011, 25(2):195-206.
[2]	Friedman SL. Mechanisms of hepatic fibrogenesis[J]. Gastroenterology, 2008, 134(6):1655-1669.
[3]	Rippe RA, Brenner DA. From quiescence to activation:gene regulation in hepatic stellate cells[J]. Gastroenterology, 2004, 127(4):1260-1262.
[4]	Cozza G, Bortolato A, Moro S. How druggable is protein kinase CK2 ?[J]. Med Res Rev, 2010, 30(3):419-62.
[5]	Wang D, Westerheide SD, Hanson JL, et al. Tumor necrosis factor alpha-induced phosphorylation of ReIA/p65 0n Ser529 is controlled by casein kinase Ⅱ[J]. J Biol Chem, 2000, 275(42):32592-32597.
[6]	Rodriguez FA. Contreras C, Bolanos-Garcia V, et al. Protein kinase CK2 as an ectokinase: the role of the regulatory CK2 beta subunit[J]. Proc Natl Acad Sci(USA), 2008, 105(15):5693-5698.
[7]	Prudent R, Cochet C. New protein kinase CK2 inhibitors: jumping out of the catalytic box[J]. Chem Biol, 2009, 16(2):112-120.
[8]	Shi D,Zhang J,Qiu L,et al.Matrine inhibits infiltration of the inflammatory gr1(hi) monocyte subset in injured mouse liver through inhibition of monocyte chemoattractant protein-1[J].Evid Based Compl Alternat Med,2013,2013:580673.
[9]	Wang W, You RL, Qin WJ, et al. Anti-tumor activities of active ingredients in compound Kushen injection[J]. Acta Pharmacol Sin, 2015, 36(6):676-679.
[10]	Yang Y, Xiu J, Zhang X, et al. Antiviral effect of matrine against human enterovirus 71[J]. Molecules, 2012, 17(9):10370-10376.
[11]	Zhang JP, Zhang M, Zhou JP, et al. Antifibrotic effects of matrine on in vitro and in vivo models of liver fibrosis in rats[J]. Acta Pharmacol Sin, 2001, 22(2):183-186.
[12]	Hu H,Wang S,Zhang C,et al.Synthesis and in vitro inhibitory activity of matrine derivatives towards pro-inflammatory cytokines[J].Bioorg Med Chem Lett,2010,20(24):7537-7539.
[13]	Xu WH, Hu HG, Tian Y, et al. Bioactive compound reveals a novel function for ribosomal protein S5 in hepatic stellate cell activation and hepatic fibrosis[J]. Hepatology, 2014, 60(2): 648-660.
[14]	Xu Y, Peng Z, Ji W, et al. A novel matrine derivative WM130 inhibits activation of hepatic stellate cells and attenuates dimethylnitrosamine-induced liver fibrosis in rats[J]. Biomed Res Int, 2015, 2015:203978.
[15]	Qian L, Liu Y, Xu Y, et al. Matrine derivative WM130 inhibits hepatocellular carcinoma by suppressing EGFR/ERK/MMP-2 and PTEN/AKT signaling pathways[J]. Cancer Lett, 2015, 368(1):126-134.

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蛋白激酶CK2α在大鼠肝纤维化病理过程中的表达变化

doi: 10.3969/j.issn.1006-0111.2015.06.010

第二军医大学药学院生化药学教研室, 上海 200433

基金项目: 国家自然科学基金项目(No.81170404)

收稿日期: 2015-06-10
修回日期: 2015-10-11

关键词:

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。

English Abstract

The expression of protein kinase CK2α in rat hepatic fibrogenesis process

Department of Biochemic Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China

Received Date: 2015-06-10
Rev Recd Date: 2015-10-11

Keywords:

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.

引用本文: