MicroRNA27a抑制肝星状细胞脂质代谢分子机制的初步研究

摘要/Abstract

摘要： 目的初步探究microRNA-27a(miR-27a)在肝星状细胞中脂质代谢的分子机制。方法 C57BL/6实验小鼠随机分组为高脂加CCL₄组和普食加CCL₄组,HE和天狼星红染色检测小鼠肝组织病理改变情况,PCR检测高脂加CCL₄组和普食加CCL₄组小鼠肝组织中miR-27a表达水平及FAS、SCD1相关mRNA表达水平。结果与对照组miR-27a 的表达量比较,实验组结果表明miR-27a在PA刺激后的LX2细胞中表达下降;对比普食加CCL₄组,高脂加CCL₄组小鼠肝组织中miR-27a表达下降,差异均具有统计学意义(P<0.05);相比较空白对照组,过表达miR-27a后的LX2细胞脂质沉积明显减轻,FAS、SCD1相关mRNA表达水平显著降低,高脂加CCL₄组小鼠促脂质合成因子FAS、SCD1相关mRNA表达上升,差异均具有统计学差异(P<0.05)。结论 miR-27a可能是通过抑制FAS、SCD1 的表达抑制肝星状细胞脂质代谢,减轻肝脏脂质沉积,延缓肝脂肪变的发生发展。

关键词: 微小RNA, 脂肪酸合酶, 硬脂酰辅酶A去饱和酶1, 非酒精性脂肪性肝病

Abstract: Objective To investigate the molecular mechanism of microRNA27a inhibiting the lipid metabolism of hepatic stellate cell. Methods LX2 cells were stimulated by palmitic acid (PA), the expression level of miR-27a was tested by PCR; After Overexpression of miR-27a, lipid deposition of LX2 cells was tested by oil red staining.The mRNA expression of FAS and SCD1 was verified by qPCR. C57BL/6 mice were randomly divided into two group: high-fatty diet with CCL₄ group(HFD+CCL₄) and low fatty diet with CCL₄ (LFD+CCL₄). The pathological changes of liver tissues in mice were detected by hematoxylin eosin (HE) and Sirius red staining. Besides, qPCR was applied to detect the relative expression of microRNA27a and the mRNA expression of FAS and SCD1 in different group. Results Comparing with the control group,the expression of miR27a in LX2 cell in experimental group decreased after stimulated by PA; In the mouse model ,the expression of miR27a in HFD with CCL₄ group also decreased, compared with LFD with CCL₄ (P<0.05).Compared with blank control group, lipid deposition in LX2 cells of overexpressing miR-27 a was significantly reduced as well as the mRNA expression of FAS and SCD1, however, the expression of FAS and SCD1 in HFD with CCL₄ group were increased (P<0.05). Conclusion MiR-27a can inhibit the lipid synthesis of hepatic stellate cells, reduce liver lipid deposition and delay the development of liver fatty change by inhibiting the expression of FAS and SCD1.This provides a new thought for the treatment of nonalchoholic fatty liver disease.

Key words: microRNA, FAS, SCD1, Nonalchoholic fatty liver disease

徐梓馨, 罗昕, 罗声政, 徐铭益, 林仁坤. MicroRNA27a抑制肝星状细胞脂质代谢分子机制的初步研究[J]. 肝脏, 2020, 25(9): 994-997.

XU Zi-xin, LUO Xin, LUO Sheng-zheng, XU Ming-yi, LIN Ren-kun. A preliminary study on the molecular mechanism of microRNA-27a inhibiting lipid metabolism of hepatic stellate cells[J]. Chinese Hepatolgy, 2020, 25(9): 994-997.

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