| 路玉洁,邹湘君,武彦芳,贾 磊,高翠贤.Gdf15对酒精性脂肪肝代谢异常的影响[J].现代生物医学进展英文版,2023,(4):630-635. |
| Gdf15对酒精性脂肪肝代谢异常的影响 |
| Effect of GDF15 on Metabolic Abnormalities of Alcoholic Fatty Liver |
| Received:April 28, 2022 Revised:May 25, 2022 |
| DOI：10.13241/j.cnki.pmb.2023.04.006 |
| 中文关键词: 酒精性脂肪肝 GDF15 脂代谢 |
| 英文关键词: Alcoholic fatty liver GDF15 Lipid metabolism |
| 基金项目:陕西省科技技术厅项目（2022SF-007） |
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| 中文摘要: |
| 摘要 目的：探讨生长分化因子15（Growth and Differentiation Factor 15， GDF15）对于酒精性脂肪肝(alcoholic fatty liver， AFL)代谢异常的影响。方法：用白酒构建酒精性脂肪肝小鼠模型然后分别给对照组和模型组尾静脉注射AAV8-GDF15过表达肝脏的GDF15分子，将小鼠共分为四组：正常+尾静脉注射对照AAV8-NC组(Con+AAV8-NC)、模型(酒精)+尾静脉注射AAV8对照病毒组(AFL+AAV8-NC)、正常+尾静脉注射过表达AAV8-Gdf15组(Con+AAV8-Gdf15)、酒精+尾静脉注射过表达AAV8-Gdf15组(AFL+AAV8-Gdf15)。对其体重、空腹血糖、葡萄糖耐量、胰岛素释放、血清脂、肝脏脂、谷丙转氨酶、谷草转氨酶含量的测定；其肝脏活组织切片使用苏木精-伊红染色法染色检测肝脏结构异常；q-PCR检测脂代谢相关分子RNA水平等观察过表达GDF15对酒精性脂肪肝的影响。结果：与Con+AAV8-N组相比，AFL+AAV8-NC组的体重下降，而过表达GDF15后AFL+AAV8-Gdf15组体重比AFL+AAV8-NC组的体重下降减少。与Con+AAV8-NC组相比，AFL+AAV8-NC组的空腹血糖升高、糖耐量及胰岛素耐量下降，过表达GDF15后AFL+AAV8-Gdf15组与AFL+AAV8-NC相比空腹血糖显著下降、糖耐量及胰岛素耐量显著升高。AFL+AAV8-NC组与Con+AAV8-NC组相比血脂TG明显升高，过表达GDF15后AFL+AAV8-Gdf15组血脂与AFL+AAV8-NC的血脂相比显著下降。与Con+AAV8-NC组相比，AFL+AAV8-NC组的肝脏重量增加，肝功能损伤程度更严重，肝脏脂肪含量增加，而过表达GDF15后AFL+AAV8-Gdf15与AFL+AAV8-NC组相比，肝脏重量、损伤程度及肝脏的脂肪含量均有显著性下降。结论：酒精性脂肪肝增加GDF15的表达，而GDF15的表达增加会改善酒精性脂肪肝的损伤及代谢异常。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the effect of Growth and Differentiation Factor 15( GDF15) on alcoholic fatty liver (AFL). Methods: A model of mouse with alcoholic fatty liver disease was constructed with liquor, and then the control group and the model group were injected with AAV8-GDF15 molecules overexpressing the liver in the tail vein, and the mice were divided into four groups - normal + tail vein injection control AAV8-NC group (Con+AAV8-NC), model (alcohol) + tail vein injection AAV8 control virus group (AFL+AAV8-NC), normal + tail vein injection overexpressed AAV8-Gdf15 group (Con+ AAV8-Gdf15), alcohol + tail vein injection overexpressed AAV8-Gdf15 group (AFL+AAV8-Gdf15). By measuring body weight, fasting blood glucose, Intraperitoneal glucose tolerance test (IPGTT), insulin release test (ITT), and using test kits for their serum lipids, liver fats, alanine transaminase (ALT), Determination of aspartate transaminase (AST); liver biopsy sections were detected by hematoxylin-eosinstaining (HE) staining to detect structural abnormalities; The effect of over expression of GDF15 on alcoholic fatty liver was observed via q-PCR detecting of lipid metabolism-related molecular RNA levels, etc. Results: Compared with the Con+AAV8-NC group, weight loss was observed in group AFL+AAV8-NC. The weight loss in the AFL+AAV8-Gdf15 group was reduced compared to AFL+AAV8-NC after over expression of GDF15. Compared with the Con+AAV8-NC group, the fasting blood glucose in the AFL+AAV8-NC group increased, and the sugar tolerance and insulin resistance decreased. After overexpression of GDF15, the AFL+AAV8-Gdf15 group decreased significantly in fasting blood glucose and increased glucose tolerance and insulin resistance compared with AFL+AAV8-NC. The AFL+AAV8-NC group was significantly elevated compared with the Con+AAV8-NC group, and the lipids of the AFL+AAV8-Gdf15 group decreased significantly compared with those in the AFL+AAV8-NC group after overexpression of GDF15. Compared with the Con+AAV8-NC group, the liver weight of the AFL+AAV8-NC group increased， the degree of liver function damage was more severe, and the fat content of the liver increased. After the expression of GDF15, the liver weight, degree of damage and fat content of the liver were significantly reduced in group AFL+AV8-Gdf15 compared with AFL+AAV8-NC group. Conclusion: Alcoholic fatty liver disease increases the expression of GDF15, and increased expression of GDF15 will improve the damage and metabolic abnormalities of alcoholic fatty liver. |
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