表皮生长因子受体对乙醇所致肝细胞损伤中脂肪酸合酶表达的影响  

Effects of epidermal growth factor receptor on fatty acid synthase expression in ethanol-induced liver injury

作　　者：赵刚[1] 董蕾[1] 李红[1] 史海涛[1] 秦斌[1] 赵红莉[1] 鲁晓岚[1] 

机构地区：[1]西安交通大学第二附属医院消化内科,西安710004

出　　处：《山西医科大学学报》2016年第8期689-693,共5页Journal of Shanxi Medical University

基　　金：陕西省自然科学基金资助项目(2012JQ4030);西安交通大学第二附属医院人才培养专项科研基金资助项目(RC(BL)201301)

摘　　要：目的观察乙醇所致原代培养小鼠肝细胞损伤中脂肪酸合酶(FASN)的表达情况,探讨表皮生长因子受体(EGFR)在此过程中可能的作用。方法常规原代培养小鼠肝细胞,随机分为对照组(生理盐水组)、乙醇组、Gefitinib组及Gefitinib加乙醇组,收集并测定细胞裂解液中丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)活性和丙二醛(MDA)浓度;提取细胞总RNA及蛋白质,分别采用real time-PCR及Western blot方法检测FASN、固醇调节元件结合蛋白(sterol regulatory element binding proteins,SREBP-1c)及p-EGFR的基因及蛋白的表达。结果经150 mmol/L乙醇作用10 h的小鼠原代培养肝细胞贴壁生长状况变差,与对照组比较,细胞裂解液中ALT、AST活性及MDA浓度显著上升(P<0.01),出现肝细胞损伤。与对照组比较,Gefitinib组肝细胞的FASN、SREBP-1c及EGFR在基因及蛋白水平均无明显变化(P>0.05),乙醇组肝细胞的FASN、SREBP-1c及p-EGFR在基因及蛋白水平表达丰度均明显升高,其差异有统计学意义(P<0.05或P<0.01)。与乙醇组比较,Gefitinib加乙醇组肝细胞中FASN及SREBP-1c的基因及蛋白表达水平显著降低(P<0.01),其p-EGFR mRNA的表达量仍处于高值,但差异无统计学意义(P>0.05),而其蛋白表达水平出现显著下降(P<0.05)。结论 FASN在正常肝细胞中仅微量表达,而在乙醇所致肝损害的肝细胞中呈高表达,其表达水平可能受EGFR调节。Objective To investigate the expression of fatty acid synthase （FASN） in ethanol-induced liver injury in primary mouse hepatocytes, and to explore the possible role of epidermal growth factor receptor（EGFR） in the process of liver injury. Methods Primary mouse hepatocytes were cultured conventionally, and randomly divided into normal control group（ saline group）, ethanol group, Gefitinib group, and Gefitinib plus ethanol group. Malondialdehyde （MDA） concentrations and activities of alanine aminotransferase （ALT） and aspartate aminotransferase（AST） were detected in cell lysates. Total RNA and protein from liver cells were extracted to measure the mRNA and protein expression of FASN, sterol regulatory element binding proteins （SREBP-1c） and EGFR by real time- PCR and Western blot. Results Compared with normal control group, MDA concentrations and activities of ALT and AST increased significantly in ethanol group（P 〈 0.01 ）. Compared with normal control group, FASN, SREBP-lc and p-EGFR expression both in gene and protein levels showed no significant changes in Gefitinib group （ P 〉 0.05 ）, but increased in ethanol group （ P 〈 0.05 or P 〈 0. 01 ）. Compared with ethanol group, the expression of FASN and SREBP-1c was decreased both in gene and protein levels in Gefitinib plus ethanol group（P 〈 0. 01 ）, p-EGFR protein expression was also significantly decreased（P 〈 0. 05 ）, while p-EGFR mRNA expression was still in the high value, but there was no significant difference （ P 〉 0. 05 ）. Conclusion FASN slightly expresses in normal liver cells, but highly expresses in ethanol-induced liver injury, which may be regulated by EGFR.

关 键 词：表皮生长因子受体 酒精性肝损害 脂肪酸合酶 酪氨酸激酶抑制剂 

分 类 号：R575[医药卫生—消化系统]