黏着斑激酶酪氨酸磷酸化促大鼠肝纤维化形成及其可能机制  

Focal adhesion kinase tyrosine phosphorylation promotes rat hepatic fibrogenesis and its possible mechanism

作　　者：张晓岚[1] 霍晓霞[1] 申建刚[1] 魏娟[1] 姜慧卿[1] 

机构地区：[1]河北医科大学第二医院消化科,河北石家庄050000

出　　处：《基础医学与临床》2007年第2期143-147,共5页Basic and Clinical Medicine

基　　金：河北省自然科学基金(301361);河北省卫生厅资助项目(2003055);河北省普通高校强势特色学科专项

摘　　要：目的探讨在肝纤维化发生中,黏着斑激酶(FAK)酪氨酸磷酸化与肝星状细胞(HSC)增殖的关系,并从细胞周期角度探讨其促HSC增殖的机制。方法采用胆总管结扎(BDL)方法建立大鼠肝纤维化模型;免疫组织化学方法测定α-平滑肌肌动蛋白(α-SMA)表达;Western blot检测p-FAK(Tyr397)、细胞周期蛋白D1(cyclin D1)和细胞周期蛋白依赖激酶4(CDK4)在肝组织中的含量。结果正常大鼠肝组织有少量α-SMA分布,随着肝纤维化发展,α-SMA阳性细胞明显增多;肝组织中p-FAK(Tyr397)、cyclin D1及CDK4蛋白表达逐渐增加,造模4周时达峰值。多元相关分析示α-SMA与p-FAK(Tyr397)正相关(r=0.964,P<0.01);α-SMA与cyclin D1、CDK4正相关(r=0.953,0.906;P<0.01);p-FAK(Tyr397)与cyclin D1、CDK4亦明显正相关(r=0.969,0.893;P<0.01)。结论FAK磷酸化促HSC增殖及肝纤维化形成机制可能与调控细胞周期相关蛋白有关。Objective To observe the relationship between phosphorylation of focal adhesion kinase （FAK） and hepatic stellate cells（HSCs） proliferation in fibrotic rat liver, and to study the mechanism of phosphorylated FAK regdating HSC proliferation. Methods Rat hepatic fibrosis was induced by bile duct ligation （BDL）. Histopathological changes were evaluated by hematoxylin and eosin staining, and by Masson＇ s trichrome method. Activated HSCs were quantified after alpha smooth muscle actin（α-SMA） staining. The proteins of p-FAK（Tyr^397）, Cyclin D1 and cyclin dependent kinase4 （CDK4） in the liver tissue were assayed by Western blot. Results ①With the development of hepatic fibrosis, the positive cells of α-SMA increased obviously. The positive areas of the rat livers in model groups at week 1 to 4 （ 12. 88% ± 2. 63%, 22. 65% ± 2. 16%, 27. 45% ± 1.86%, 35.25% ± 2. 34% ） were larger than that in control group （5.88% ± 1.46% ）, P 〈 0. 01. ②Western blot analysis showed that in the sham-operated group, the p-FAK（Tyr^397） , Cyclin D1 and CDK4 was less expressed. But with the development of liver fibrosis, the expression of the three kinds of proteins increased gradually in model groups at week 1 to 4. ③α-SMA correlated with p-FAK （Tyr397） positively, r value was 0. 964, P 〈 0. 01 ; α-SMA correlated with Cyclin D1 and CDK4 positively, r value was 0. 953 and 0. 906 respectively, P 〈 0. 01 ; p-FAK（Tyr^397） correlated with Cyclin D1 and CDK4positively, r value was 0. 969 and 0. 893 respectively,P 〈0. 01. Conclusion In hepatic fibrogenesis process, HSCs become active and proliferated, while the expression of p-FAK （Tyr^397）, Cyclin D1 and CDK4 is increased, p-FAK （Tyr^397 ） is correlated positively with Cyclin D1 and CDK4. The mechanism of phosphorylated FAK promoting hepatic fibrosis probably is concerned with regulating cell cycle related protein.

关 键 词：肝纤维化 肝星状细胞 黏着斑激酶 细胞周期蛋白D1 细胞周期蛋白依赖激酶4 

分 类 号：R575.2[医药卫生—消化系统]