武汉云克隆科技股份有限公司

Abstract：

This study investigated the immunomodulating effect of melatonin on toll-like receptor (TLR)-stimulated signal transduction. Rats were subjected to 60 min of ischemia followed by 1 or 5 hr of reperfusion. Melatonin (10 mg/kg) or the vehicle was administered intraperitoneally 15 min prior to ischemia and immediately before reperfusion. Melatonin treatment significantly reduced the level of serum alanine aminotransferase activity. Increased levels of TLR3 and TLR4 protein expression induced by ischemia/reperfusion (I/R) were attenuated by melatonin. Serum level of high-mobility group box 1 (HMGB1), a potent alarmin of the TLR system, increased significantly in the I/R group, and melatonin inhibited this release. Melatonin suppressed the increase in myeloid differentiation factor 88 (MyD88) protein expression, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) phosphorylation and nuclear translocation of nuclear factor κB (NF-κB) and phosphorylated c-Jun, a component of activator protein 1. The increased level of toll-receptor-associated activator of interferon (TRIF) expression, phosphorylation of interferon (IFN) regulatory factor 3 (IRF3) and serum IFN-β was attenuated by melatonin. Melatonin attenuated the levels of tumor necrosis factor alpha (TNF-α), interleukin (IL)-6 and inducible nitric oxide synthase (iNOS) protein and mRNA expression, while the level of heme oxygenase-1 (HO-1) was augmented. Our results suggest that melatonin ameliorates I/R-induced liver damage by modulation of TLR-mediated inflammatory responses.

摘要：

本研究探讨褪黑素通过影响Toll样受体(TLR)信号转导的免疫调节作用。将实验动物大鼠缺血处理1小时在再灌注处理5小时。于缺血前15分钟及再灌注前立刻腹腔注射褪黑素(10mg/kg)或溶剂。褪黑素处理组中血清丙氨酸氨基转移酶活性显著降低。褪黑素抑制缺血再灌注(I/R)诱导TLR 3和TLR 4蛋白表达。高迁移率族蛋白1(HMGB 1)的血清水平是TLR系统的一种强效蛋白，其血清水平在I/R组显著升高，褪黑激素能抑制这种释放。褪黑激素抑制髓系分化因子88(MyD88)蛋白表达、细胞外信号调节激酶(ERK)和c-Jun氨基末端激酶(JNK)磷酸化、NF-κB和激活蛋白1磷酸化c-Jun的核转运；褪黑素可降低Toll受体相关干扰素激活因子(TRIF)表达、干扰素调节因子3(IRF 3)磷酸化和血清IFN-β水平；褪黑素可降低肿瘤坏死因子α(TNF-α)、白介素6(IL-6)、诱导型一氧化氮合酶(INOS)的蛋白和mRNA表达，而升高血红素氧合酶-1(HO-1)的水平。本研究表明褪黑素通过调节TLR介导的炎症机制改善I/R诱导的肝脏损伤。

使用试剂原文信息： A commercial rat IFN-b ELISA kit (USCN Life Science Inc., Wuhan, China) was used for quantification of the serum level of IFN-b.