中文摘要：

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。

英文摘要：

Objective To detect the expression change of Sec61α in hepatic steatosis and its possible mechanism. Methods L02 liver cells were treated with palmitic acid and oleic acid mixture to establish an in vitro cellular model of nonalcoholic fatty liver disease （NAFLD） （ steatosis group）. Those cells without treat- ment were assigned into a control group. The steatotic hepatocytes were further incubated with or without a Sec61 inhibitor Eeyarestatin I （ inhibitor group or DMSO group, respectively）. The cells were collected at 0, 2, 4, 8, 12, and 16 h after induction for oil red O staining, qRT-PCR, or Western blotting to detect the expression of Sec61α, GRP78, GRP94, and Bcl-2. Results Liver cell steatosis was induced by the palmitic acid and oleic acid mixture. As compared to the control group, the hepatocytes in the steatosis group showed a decrease of See61 α expression in early stages （2 and 4 h, P 〉 0. 05 ）, but an increased in late stages （8 and 12 h, P 〈0. 05 ）. Moreover, GRP78 was up-regulated in 8 h after induction and reached the highest level at 16 h after induction （P 〈0. 01 ）. Furthermore, Eeyarestatin I significantly attenuated hepatocytic steatosis as well as the expression of Sec61α and GRP78 proteins （P 〈 0. 01 ） , but upregulated GRP94 and Bcl-2 expression （P 〈 0. 01 ）. Conclusion Sec61α may be involved in hepatic steatosis by regulating liver cell endoplasmic reticulum stress.