Department of Molecular Biology, Norman Bethune College of Medicine, Jilin University, Changchun 130021, PR China.
Int Immunopharmacol. 2012 Mar;12(3):526-33. doi: 10.1016/j.intimp.2012.01.007. Epub 2012 Jan 30.
Increasing evidence suggests that the alcoholic liver injury is associated with activation of Toll-like receptors (TLRs) and the consequent over-production of inflammatory cytokines such as TNF-α. However, few studies have evaluated the effect of CpG ODN, a TLR9 agonist, on alcoholic liver injury. In this study, an animal model of acute alcohol-induced liver injury was established by administering the mice with alcohol at 7 g/kg intragastrically once. Using the model, 2216, an A-type CpG ODN, was found able to dramatically elevate serum ALT levels and aggravate pathological changes of liver in mice. In contrast, 2006, a B-type CpG ODN, caused elevation of serum ALT levels with no visible aggravation of liver pathological changes; YW002, a C-type CpG ODN, caused no elevation of serum ALT levels and seemed able to lessen pathological changes in the liver of the mice. Real-time RT-PCR revealed that 2216 dramatically up-regulated the expression of TLR9 and TNF-α and YW002 was unable to up-regulate expression of TLR9 and TNF-α, instead up-regulate the expression of IFN-α in the livers of the model mice. The data suggest that 2216 could aggravate alcohol-induced liver injury by inducing the up-regulation of hepatic TLR9 and TNF-α and that YW002 could alleviate the pathological changes induced by acute alcohol intake by up-regulating IFN-α, possibly.
越来越多的证据表明，酒精性肝损伤与 Toll 样受体（TLRs）的激活有关，继而导致 TNF-α 等炎症细胞因子的过度产生。然而，很少有研究评估 TLR9 激动剂 CpG ODN 对酒精性肝损伤的影响。在这项研究中，通过给小鼠口服 7g/kg 的酒精来建立急性酒精诱导的肝损伤动物模型。利用该模型发现，A 型 CpG ODN 2216 能够显著提高血清 ALT 水平并加重小鼠肝脏的病理变化。相比之下，B 型 CpG ODN 2006 虽然能提高血清 ALT 水平，但对肝脏病理变化没有明显加重；C 型 CpG ODN YW002 则没有提高血清 ALT 水平，似乎能够减轻模型小鼠肝脏的病理变化。实时 RT-PCR 显示，2216 能显著上调 TLR9 和 TNF-α 的表达，而 YW002 不能上调 TLR9 和 TNF-α 的表达，反而能上调模型小鼠肝脏中 IFN-α 的表达。这些数据表明，2216 可能通过诱导肝 TLR9 和 TNF-α 的上调来加重酒精诱导的肝损伤，而 YW002 可能通过上调 IFN-α 来缓解急性酒精摄入引起的病理变化。
