| 冯之文,鲍胜华,张文君,等.微小 RNA-378调控小鼠急性肝衰竭作用机制的研究[J].安徽医药,2021,25(9):1797-1800. |
| 微小 RNA-378调控小鼠急性肝衰竭作用机制的研究 |
| Research on the mechanism underlying the regulation of miR-378 on acute liver failure in mice |
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| DOI：10.3969/j.issn.1009-6469.2021.09.023 |
| 中文关键词: 肝功能衰竭，急性 微小 RNA-378 胱天蛋白酶 -3 凋亡 小鼠，近交 BALB C 脂多，miR-3，的， |
| 英文关键词: Liver failure, acute MiR-378 Caspase-3 Apoptosis Mice, inbred BALB C |
| 基金项目:皖南医学院中青年基金项目( KY24680368) |
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| 中文摘要: |
| 目的探究微小 RNA-378(miR-378)调控小鼠急性肝衰竭的作用机制。方法将 36只雄性巴比塞小鼠以随机数字表法均分为实验组和对照组。实验组腹腔注射 D氨基半乳糖( D-GalN)800 mg/kg联合脂多糖 10 μg/kg诱导急性肝衰竭，对照组为腹腔内注射等量的生理盐水。两组在诱导后 0、1、3、5、7、9h处死小鼠取静脉血和肝组织，每个时间点有 3只实验鼠。检测两组在各时间点血清中丙氨酸氨基转移酶( ALT)、天冬氨酸氨基转移酶( AST)水平，酶联免疫吸附测定( ELISA)检测血清中肿瘤坏死因子 -α(TNF-α)、白细胞介素 -6(IL-6)水平，逆转录聚合酶链反应( RT-PCR)测定肝组织中的胱天蛋白酶 -3(Caspase-3)、 TNF-α及 IL-6 mRNA表达量，探针法确定肝组织中 miR-378表达量，蛋白质印迹法( Western blotting)检测 Caspase-3蛋白表达量。结果实验组 ALT/AST水平逐渐升高且在诱导后 7h达到峰值，对照组 ALT/AST未见明显变化。相较对照组，实验组在诱导后 1h和 7 h TNF-α/IL-6血清浓度及 mRNA水平明显升高；实验组在诱导后 5h［(0.003 8±0.000 3)比( 0.005 4±0.000 3)，P<0.05］和 7h［(0.001 4± 0.000 5)比( 0.005 4±0.000 3)，P<0.05］miR-378表达量明显降低， Caspase-3 mRNA［5h(0.005 2±0.000 3)， 7h(0.007 0±0.000 6)比( 0.003 3±0.000 1)均 P<0.05］和蛋白［5h(0.867±0.012)7h(1.062±0.039)比( 0.577±0.035)均 P<0.05］表达量升高。结论在小鼠 D-GalN联合糖诱导的急性肝衰竭模型中， 78表达量的下调促进了 Caspase-3活化，增强了肝细胞凋亡活动，进而调控急性肝衰竭的发展。 miR-378可作为治疗急性肝衰竭新靶点。 |
| 英文摘要: |
| Objective To investigate the effects of microRNA(miR)-378 on mouse acute liver failure.Methods Thirty-six male BALB/c mice were randomly divided into experimental group and control group according to the random number table method. Mice inthe experimental were intraperitoneally injected with 800 mg/kg D-galactosamine (D-GalN) and 10 μg/kg lipopolysaccharide (LPS),while mice in the control group were injected with equal amount of saline. The mice of the two groups were sacrificed at different timepoints(0,1,3,5,7,9 h) for blood and liver tissue, with 3 mice at each time point. The levels of serum aminotransferase (ALT&AST) at different time points were measured. The levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 were measured by ELISA. The expression of Caspase-3, TNF-α and IL-6 mRNA in liver tissue were examined by reverse transcription-polymerase chain reaction (RTPCR). The expression of miR-378 was measured by TaqMan Universal PCR Master Mix. We determined the expression of Caspase-3 by Western blotting.Results The enzyme levels (ALT/AST) in the experimental group elevated gradually, peaking at 7 h, while ALT/ASTlevels in the control group were not significantly changed. Compared with those in the control group, the mRNA levels and serum concentrations of TNF-α/IL-6 were higher at 1 h and 7 h in experimental group. In the experimental group, miR-378 was down-regulated at 5 h[(0.003 8±0.000 3) vs. (0.005 4±0.000 3)](P<0.05) and 7 h[(0.001 4± 0.000 5) vs. (0.005 4±0.000 3)](P<0.05), while the mRNA [5 h (0.005 2±0.000 3),7 h(0.007 0±0.000 6) vs. (0.003 3±0.000 1), both P<0.05] and protein[5 h(0.867±0.012), 7 h(1.062±0.039) vs. (0.577±0.035), both P<0.05] of Caspase-3 were up-regulated.Conclusions In the mouse ALF model induced by D-GalN/LPS, the down-regulation of miR-378 promotes the activation of Caspase-3,enhances hepatocytes apoptosis in liver. MiR-378 may serve as a potential therapeutic target for the treatment of ALF. |
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