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肝细胞脂肪变性模型中Sec61α的表达及可能作用机制

, PP. 755-758

Keywords: 脂肪变性,内质网应激,Secα,GRP,GRP,Bcl-

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Abstract:

目的探讨肝细胞脂肪变性模型中Sec61α的表达及可能机制。方法用软脂酸与油酸混合物诱导L02肝细胞发生脂肪变性,建立非酒精性脂肪性肝病肝细胞体外模型,按0、2、4、8、12h及16h收获细胞;随后应用Sec61抑制剂EeyarestatinⅠ处理肝细胞,分为正常对照组、脂肪变性组、DMSO组及抑制剂组,通过油红O染色、qRT-PCR及Westernblot检测Sec61α、GRP78、GRP94、及Bcl-2的表达变化。结果软脂酸与油酸混合物成功诱导肝细胞发生脂肪变性。与对照细胞相比,脂肪变肝细胞Sec61αmRNA相对表达量在脂肪变早期下降(2、4h,P>0.05),晚期升高(8、12h,P<0.05);GRP78在8h开始升高,16h达峰(P<0.01)。Sec61α与GRP78的蛋白水平与mRNA水平表达在时间梯度上变化一致。EeyarestatinⅠ处理显著减轻肝细胞脂肪变程度;与脂肪变性组相比,抑制剂组肝细胞Sec61α、GRP78明显降低(P<0.01),GRP94、Bcl-2则显著升高(P<0.01)。结论Sec61α可能通过调节肝细胞内质网应激,参与肝细胞脂肪变的形成。

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