Src家族相关激酶（Fgr、Hck、Lyn）/SSeCKS在非酒精性脂肪性肝炎中的作用机制  

Mechanism of expression of the Src family kinases （Fgr, Hck, Lyn） and SSeCKS in non-alcoholic steatohepatitis

作　　者：张玲燕 邵建国[2] 肖锋[2] 陈琳[2] 何红梅[3] 

机构地区：[1]南通市第六人民医院 [2]南通市第三人民医院 [3]南京中医药大学

出　　处：《中华肝脏病杂志》2015年第5期363-367,共5页Chinese Journal of Hepatology

基　　金：江苏省科技厅自然科学基金（BK2011394）;南通市科技局社会事业科技创新与示范（HS2013054）

摘　　要：目的 探讨Src家族相关激酶（Fgr、Hck、Lyn） /SSeCKS在非酒精性脂肪性肝炎（NASH）中的作用及其可能的机制.方法 体外实验中对枯否细胞用含0.5％ CCl4完全培养液刺激,正常组常规培养,培养2h后用PT-PCR检测SSeCKS和Hck、Fgr、Lyn的mRNA表达水平.体内实验中选用SD雄性大鼠,采用高脂饮食饲养法制备NASH大鼠模型,设模型组、正常组.实验结束后处死各组大鼠,检测肝脏脂肪变及炎症程度,用免疫组织化学法检测SSeCKS和Hck、Fgr、Lyn的蛋白表达水平.计量资料两组均数比较用t检验,多组均数比较用方差分析;变量间相互关系采用Pearson直线相关分析.结果 体外实验结果显示SSeCKS、Lyn、Hck、Fgr的mRNA在枯否细胞中均有表达;体内实验结果提示Lyn、Hck在正常肝组织枯否细胞低表达,炎症刺激时高表达,与炎症程度呈正相关（P＜ 0.01）;SSeCKS则在正常肝组织枯否细胞低表达,炎症刺激时表达减少,与炎症程度呈负相关（P＜ 0.01）;Fgr在正常肝脏组织Kupffer细胞极低表达,炎症刺激后几乎不表达;且Lyn、Hck与SSeCKS的表达呈负相关（P＜ 0.01）,其中与Hck呈中度负相关（r=-0.508,P＜0.01）,与Lyn呈低度负相关（r=-0.398,P＜0.01）,Hck与Lyn的表达呈极高正相关（r=0.942,P＜ 0.01）. 结论 Src家族相关激酶（Lyn、Hck、Fgr）/SSeCKS参与了NASH的发生和发展,且相互间有一定联系,可作为NASH炎症反应的一个潜在调控靶点.Objective To investigate the role of Src family kinases （Fgr,Hck,Lyn） and the major protein kinase C substrate SSeCKS in non-alcoholic steatohepatitis （NASH） and determine the possible mechanism regulating differential expression.Methods Kupffer cells were stimulated with CCL4 and effect on SSeCKS,Hck,Fgr,and Lyn expression was detected by real-time reverse transcription-PCR.Male Sprague-Dawley rats were used to create a NASH model by feeing a high fat diet.The modeled rats were divided into a model group and a normal group.After sacrifice,the extent of hepatic steatosis and inflammation was assessed,and the expression levels of SSeCKS and Hck,Fgr,Lyn were detected by immunohistochemical staining.Results Expression of Lyn and Hck was decreased in the CCL4-stimulated Kupffer cells and the change in expression level was positively associated with levels of inflammatory stimuli （p 〈 0.01）.The change in expression of SSeCKS in the CCL4-stimulated Kupffer cells was negatively correlated with inflammatory stimuli （p 〈 0.01）.Fgr expression was very low in the unstimulated Kupffer cells and was not affected by the exposure to inflammatory stimuli.The number of inflammatory cells in the liver tissues of rars were negatively correlated with expression of Lyn,Hck and SSeCKS （p 〈 0.01）,with low negative correlation for Lyn （r =-0.398,p 〈 0.01） and moderate negative correlation for Hck （r=-0.508,p 〈 0.01）;the Lyn and Hck expression levels were highly positively correlated （r =0.942,p 〈 0.01）.Conclusion Src family kinases （Lyn,Hck and Fgr） and SSeCKS are involved in development and progression of NASH,and their differential expression patterns are associated to a certain extent.The factors may represent potential targets of therapy for NASH-related inflammation.

关 键 词：脂肪肝 Src家族相关激酶 

分 类 号：R575.5[医药卫生—消化系统]