FGF21在小鼠非酒精性脂肪肝病程中的变化及与SREBP的相关性

FGF21 Expression During the Course of Mice NAFLD and Its Correlation with SREBP

【目的】探讨成纤维细胞生长因子(FGF21)在小鼠非酒精性脂肪肝病程中肝组织和血清中的变化及其与胆固醇调节元件结合蛋白(SREBP)的相关性,探讨其中的可能机制。【方法】分别给予C57BL/6小鼠素食和高脂饮食喂养1、9、18周,Western blot和实时荧光定量RT-PCR检测肝脏组织FGF21和SREBP的表达,并分析二者的相关性;ELISA法检测小鼠血清的FGF21水平,分析血清FGF21水平与肝组织FGF21的蛋白和m RNA水平的相关性。【结果】高脂饮食喂养至9周时,小鼠肝脏的大体外观呈典型脂肪肝表现,至18周时HE染色可见肝细胞内大量的脂质颗粒聚集。与素食喂养小鼠相比,小鼠肝组织FGF21 m RNA水平在高脂饮食喂养至9周和18周时明显升高(均P<0.05),与高脂饮食的时间呈正相关(r=0.952,P=0.000)并同时与SREBP m RNA水平正相关(r=0.725,P=0.000)。而与素食喂养小鼠相比,小鼠肝组织FGF21蛋白在高脂饮食喂养至9周和18周时明显降低(P<0.05),SREBP蛋白表达则呈相反的趋势。血清的FGF21水平,与素食喂养相比,在高脂饮食喂养至9周和18周时明显升高(均P<0.05),与高脂饮食的时间呈正相关(r=0.944,P=0.000),与肝组织的FGF21蛋白水平负相关(r=-0.704,P=0.000),与FGF21 m RNA水平正相关(r=0.910,P=0.000)。【结论】在小鼠脂肪肝的逐渐进展中,肝组织FGF21 m RNA水平升高,蛋白水平降低,血清水平升高,并伴随SREBP的表达升高,提示肝脏中FGF21转录合成增加同时分泌亦明显增加,并与肝脏脂质合成及沉积密切相关。

【Objective】 To investigate the fibroblast growth factor 21（FGF21） expression in liver tissue and serum from different stage of mice nonalcoholic fatty liver disease（NALFD） and its correlation with SREBP. 【Method】C57BL / 6 mice were fed with chow diet and high fat diet（HFD） for 1, 9, and 18 weeks. Expressions of FGF21 and SREBP in liver tissue of mice were detected by western blot and real time RT-PCR. Serum FGF21 was examined using ELISA. The correlation of FGF21 and SREBP was statistically analyzed. 【Result】 The liver of mice exhibited typical appearance of fatty liver after 9 weeks of HFD. A large amount of fat granules accumulation was found in hepatocytes from mice fed with HFD for 18 weeks. Compared with mice fed with chow diet, FGF21 m RNA level in liver tissue from mice fed with HFD began dramatically higher on 9th and 18 th week of HFD（both P〈0.05）, with positive correlation to the duration of HFD（r = 0.952, P = 0.000） and the SREBP m RNA level（r = 0.725, P = 0.000）. On the other hand,FGF21 protein expression in liver tissue from mice fed with HFD statistically decreased on 9th and 18 th week of HFD compared with mice of chow diet（both P〈0.05）. Opposite changes were found in the expression of SREBP protein. Furthermore, compared with mice of chow diet, serum FGF21 of HFD mice wasobviously higher on 9th and 18 th week of HFD（both P〈0.05）, with positive correlation to the duration of HFD（r = 0.944,P = 0.000） and the FGF21 m RNA level of liver tissue（r = 0.910, P = 0.000）, and negative correlation to the protein expression of FGF21 in liver tissue（r =-0.704,P = 0.000）. 【Conclusion】 In the course of mice NAFLD, FGF21 m RNA level of liver tissue increased, protein expression decreased, and serum level became higher, accompanying by the elevation of SREBP in liver. That suggests a high secretion of FGF21 would appear with a high level of transcription and synthesis of FGF21 in liver under HFD, which is closely correlated with hepatic steatosis.