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二甲双胍(metformin,MET)除具降糖效应外,还可发挥抗氧化及抗炎等药理效应,本研究探讨了MET在对乙酰氨基酚(acetaminophen,APAP)诱导的中毒性肝炎中的潜在保护效应。由于MET的部分效应依赖于腺苷酸活化蛋白激酶(AMP activated protein kinase,AMPK),本研究也尝试采用AMPK抑制剂dorsomorphin阻断MET在APAP模型中的效应,采用AMPK激活剂A-769662模拟MET的效应。结果显示:MET处理可显著抑制APAP诱导的血浆中天冬氨酸转氨酶(aspartate transaminase,AST)与丙氨酸转氨酶(alanine transaminase,ALT)水平、丙二醛(malondialdehyde,MDA)含量、过氧化氢酶(catalase,CAT)活性、肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)与白介素-6(interleukin-6,IL-6)浓度的上升,明显减轻APAP导致的肝组织病理学异常。AMPK抑制剂共同处理不能阻断MET对APAP模型中ALT及AST水平上升的抑制效应,AMPK激活剂处理不能模拟MET对ALT及AST水平的抑制效应。本研究结果提示:MET可有效减轻APAP诱导的中毒性肝炎,这一效应不依赖于AMPK。
In addition to its hypoglycemic effect, metformin (MET) can exert pharmacological effects such as anti-oxidation and anti-inflammatory. This study explored the potential protective effect of MET on toxic hepatitis induced by acetaminophen (APAP) . Because part of the effect of MET is dependent on AMP activated protein kinase (AMPK), this study also attempted to block the effect of MET in the APAP model using AMPK inhibitor dorsomorphin. The AMPK activator A-769662 was used to simulate MET Effect. The results showed that MET treatment significantly inhibited APAP-induced plasma aspartate transaminase (AST) and alanine transaminase (ALT) levels, malondialdehyde (MDA) The activity of catalase (CAT), the increase of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) concentration and the alleviation of pathological abnormalities of liver tissue . AMPK inhibitor co-treatment failed to block the inhibitory effect of MET on the increase of ALT and AST levels in APAP model. AMPK activator treatment did not simulate the inhibitory effect of MET on ALT and AST levels. Our results suggest that MET may be effective in reducing APAP-induced toxic hepatitis, an effect that is independent of AMPK.