AMPK激活剂减轻TNF-α诱导的爆发性肝损伤

发布时间：2018-04-24 08:29

本文选题：腺苷酸活化蛋白激酶 + 肿瘤坏死因子　；参考：《基因组学与应用生物学》2017年04期

【摘要】：探讨腺苷酸活化蛋白激酶(AMP activated protein kinase,AMPK)激活剂A-769662对肿瘤坏死因子α(tumor necrosis factor alpha,TNF-α)诱导的爆发性肝损伤中肝细胞凋亡的影响及机制。本研究在雄性BALB/c小鼠经腹腔内注射肿瘤坏死因子α(tumor necrosis factor alpha,TNF-α)及D氨基半乳糖胺(D-galactosamine,D-Gal),诱导爆发性肝炎模型。实验分为4组:正常对照组、A-769662单独处理组、模型组和A-769662干预组。采用比色法检测血浆转氨酶活性及肝组织中caspase-8、caspase-9、caspase-3的相对活性,Western blotting法检测肝组织中激活型caspase-3蛋白水平,TUNEL法检测肝细胞凋亡,HE染色观察肝组织病理变化,并记录各组小鼠生存情况。A-769662干预抑制了TNF-α/D-Gal诱导的肝组织中caspase-8、caspase-9、caspase-3的活性和激活型caspase-3蛋白表达水平的升高,显著减少肝细胞凋亡数目,明显下调血浆中天冬氨酸氨基转氨酶(aspartate transaminase,AST)与丙氨酸氨基转氨酶(alanine transaminase,ALT)水平,减轻肝组织病理学改变,提高小鼠生存率。AMPK激活剂A-769662在TNF-α诱导的爆发性肝损伤中,可发挥抗凋亡保护效应,这可能是其在保肝效应的新机制。
[Abstract]:To investigate the effect and mechanism of AMP activated protein kinase- AMPK activator A-769662 on hepatocyte apoptosis induced by tumor necrosis factor alpha-TNF- 伪. In this study, the male BALB/c mice were injected intraperitoneally with TNF- 伪 and D-galactosamine D-Galan to induce explosive hepatitis. The experiment was divided into 4 groups: normal control group A-769662 treatment group, model group and A-769662 intervention group. The activity of plasma aminotransferase and the relative activity of caspase-8 caspase-9 caspase-3 in liver tissue were detected by colorimetric assay. Western blotting assay was used to detect the level of activated caspase-3 protein in liver tissue. Tunel method was used to detect the apoptosis of hepatocytes and HE staining was used to detect the pathological changes of liver tissue. The survival status of mice in each group was also recorded. A-769662 intervention inhibited the increase of caspase-8 caspase-9 caspase-3 activity and the expression of activated caspase-3 protein in liver tissue induced by TNF- 伪 / D-Gal, and significantly reduced the number of hepatocyte apoptosis. The levels of aspartate transaminase (AST) and alanine transaminase (alanine transaminase) in plasma were significantly down-regulated, and liver histopathological changes were alleviated, and the survival rate of mice was increased by AMPK activator A-769662 in TNF- 伪 induced liver injury. This may be a new mechanism in protecting liver.
【作者单位】：重庆医科大学病理生理学教研室;重庆文理学院校医院;重庆医科大学干细胞与组织工程研究室;
【基金】：国家自然科学基金项目(81370179)资助
【分类号】：R575

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