| 王彪,袁娜,张永虎,曾良.野黄芩素通过PI3K/Nrf2/HO-1途径减轻LPS诱导的大鼠急性肺损伤.[J].中南医学科学杂志.,2016,(4):409-413. |
| 野黄芩素通过PI3K/Nrf2/HO-1途径减轻LPS诱导的大鼠急性肺损伤 |
| Scutellarein Reduces LPS-induced Acute Lung Injury via Regulation of PI3K/Nrf2/HO-1 in Endotoxemic Rats |
| 投稿时间：2016-03-28 修订日期：2016-06-27 |
| DOI： |
| 中文关键词: 野黄芩素 急性肺损伤 血红素氧合酶1 |
| 英文关键词:Scutellarein acute lung injury hemeoxygenase-1 |
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| 中文摘要: |
| 目的 探讨野黄芩素(SCT)对脂多糖(LPS)诱导的急性肺损伤(ALI)大鼠表达血红素氧合酶-1(HO-1)的机制。方法大鼠静脉内注射LPS(30 mg/kg)以诱导ALI。1h后分别给予不同浓度的SCT(0.1,0.5和1.0 mmol/kg)静脉注射。获肺组织标本,实时定量PCR和Western blot分别检测血红素氧合酶-1(HO-1)mRNA及蛋白的表达；比色法检测HO-1酶活性；HE染色观察病理学改变情况。提取组织总蛋白和核蛋白,Western blot检测PI3K磷酸化以及Nrf2核转位情况,同时观察SCT处理前后对大鼠血浆中TNF-α,IL-6和IL-10水平的影响。结果LPS注射后肺组织中HO-1 mRNA和蛋白表达水平有所增加,而SCT处理后能进一步上调HO-1表达水平,并能增强其酶活性。同时,SCT也可促进PI3K磷酸化,并能诱导转录因子Nrf2核转位。此外,0.5和1.0 mmol/kg的SCT能减少大鼠血浆中TNF-α和IL-6含量,并能进一步增加IL-10水平。HO-1抑制剂SnPP处理后可消除SCT对细胞因子的影响。结论SCT可能通过激活PI3K/Nrf2诱导HO-1表达来减轻LPS所致炎症反应。 |
| 英文摘要: |
| Objective To observe the molecular mechanism of Scutellarein-induced heme oxygenase 1 (HO-1) expression in endotoxemic acute lung injury rat.MethodsRats were administered LPS (30 mg/kg) by intravenous infusion to induce ALI.Scutellarein (0.1,0.5 and 1.0 mmol/kg) was given 1 h after LPS initiation.Expression of HO-1 mRNA and protein in lungs were detected by real time PCR and Western blot,respectively.The enzymic activity of HO-1 was detected by colorimetric method;The tissue injury was analyzed by histopathology.Phosphorylation of PI3K and nuclear translocation of Nrf2 were measured by Western blot.The content of TNF-α,IL-6 and IL-10 were measured by ELISA in serum.ResultsLPS caused a slight HO-1 induction both at the mRNA and protein level,whereas administration of Scutellarein significantly induced higher HO-1 expression and enzymic activity,as compared with the LPS group.In addition,Scutellarein could also induce PI3K phosphorylation and Nrf2 nuclear translocation.Furthermore,0.5 and 1.0 mmol/kg of Scutellarein could attenuate plasma levels of TNF-α and IL-6,and further increased IL-10 levels compared with the LPS group.However,the beneficial effects of Scutellarein on cytokines expression were reversed by HO-1 inhibitor SnPP.ConclusionsScutellarein induces acute lung injury of endotoxemic rat expression of heme oxygenase-1 by activation of PI3K/Nrf2 pathway. |
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