肝细胞脂肪性病变对胰高血糖素样肽1受体表达的影响

摘要

Objective To observe the expression of Glucagon-like peptide-1 receptor(GLP-1R) in the ob/ob mice liver and evaluate the effect of palmitic acid on GLP-1R in the HepG2 cell. Methods (1) we selected 5 10-week old male ob/ob mice and 5 their lean littermates. Collected their liver tissues, RT-PCR was used to detect GLP-1R mRNA expression in the liver, and the protein of GLP-1R was assayed by Western-blot and immunohistochemistry. (2) HepG2 cells were treated with different concentrations of palmitic acid, after 24 hours treatment, RT-PCR and Western blot were used to detect the change of mRNA and protein expression levels of GLP-1R. Results Compared with the littermates, the GLP-1R mRNA and protein in the liver tissues of ob/ob mice were significantly decreased (P<0.01), and the palmitic acid can reduce the mRNA and protein expression of GLP-1R in HepG2 cells, the effect was a dose-dependent manner(P<0.05). Conclusions GLP-1R is present in the liver, and the excessive fat deposition in the hepatocytes could decrease the expression of GLP-1R, which would affect the sensitivity of liver to the GLP-1.%目的：观察胰高血糖素样肽1受体（GLP-1R）在ob/ob小鼠肝脏组织中的表达情况以及棕榈酸处理对肝癌细胞株 HepG2细胞 GLP-1R 的影响。方法（1）选择10周龄的雄性 ob/ob 小鼠（C57BL/6J-Lepob/J）与其同窝野生对照型小鼠各5只，取其肝脏组织，RT-PCR方法检测肝脏组织中GLP-1R基因的表达，Western blot法检测GLP-1R蛋白的表达水平，免疫组织化学染色法对肝脏组织进行染色观察。（2）不同浓度棕榈酸对待HepG2细胞24 h后，Western blot 法检测GLP-1R蛋白表达情况，RT-PCR法检测对细胞GLP-1R mRNA的影响。结果 GLP-1R在ob/ob小鼠肝脏中表达明显下降，蛋白表达水平分别为：0.7897±0.1458 vs.0.1361±0.0290，mRNA表达水分别为：0.8038±0.1222 vs.0.4234±0.1777，与对照组相比差异有统计学意义（P＜0.005）。随着棕榈酸浓度的升高，HepG2细胞GLP-1R水平在mRNA水平与蛋白水平均逐渐下降，且在200μmol/L时出现统计学差异。结论肝脏存在GLP-1R表达，脂肪的过度沉积可显著降低肝脏GLP-1R表达水平，从而影响肝脏对GLP-1的敏感性。