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目的探讨槲皮素诱导Ⅰ型血红素氧化酶(HO-1)对肝细胞酒精性氧化损伤的保护效应及相关信号通路。方法乙醇(100 mmol/L)孵育的人原代肝细胞经槲皮素(100μmol/L)处理24h后,测定细胞HO-1活性、Nrf2转位表达及细胞相应的氧化损伤程度;在此基础上,联合应用HO-1及各(MAPK)通路抑制剂,观察上述指标的变化。结果槲皮素处理使HO-1进一步升高,并明显减轻乙醇孵育所导致的细胞GSH耗竭、MDA升高及胞内门冬氨酸转氨酶(AST)与乳酸脱氢酶(LDH)的释放;HO-1诱导剂血红素也具有类似的效应,而HO-1抑制剂锌原卟啉Ⅸ及p38与细胞外信号调节激酶(extracellular regulated protein kinase,ERK)抑制剂(SB203580与PD98059)则明显抑制了Nrf2的转位活化及槲皮素的保护效应。结论槲皮素通过诱导HO-1保护肝细胞免受酒精性氧化损伤,其信号通路与p38及ERK活化促使Nrf2转位入核启动HO-1表达有关。
Objective To investigate the protective effects of quercetin-induced type I heme oxygenase (HO-1) on alcoholic oxidative damage in hepatocytes and related signaling pathways. Methods Human primary hepatocytes incubated with ethanol (100 mmol / L) were treated with 100μmol / L quercetin for 24 hours to determine the activity of HO-1, the translocation of Nrf2 and the corresponding degree of oxidative damage. Based on this, On the combination of HO-1 and each (MAPK) pathway inhibitor, observed changes in these indicators. Results The quercetin treatment increased the HO-1 level and significantly decreased the cellular GSH depletion, the increase of MDA and the release of intracellular aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) by ethanol incubation. HO-1 inducing agent hemoglobin also had a similar effect, while HO-1 inhibitor zinc protoporphyrin Ⅸ and p38 and extracellular regulated protein kinase (ERK) inhibitors (SB203580 and PD98059) were significantly inhibited Nrf2 translocation activation and quercetin protective effect. CONCLUSIONS: Quercetin protects hepatocytes from oxidative oxidative damage by inducing HO-1, and its signaling pathway is related to the activation of p38 and ERK to activate Nrf2 translocation into the nucleus and initiate HO-1 expression.