Moderate (2%, v/v) Ethanol Feeding Alters Hepatic Wound Healing after Acute Carbon Tetrachloride Exposure in Mice.
Moderate (2%, v/v) Ethanol Feeding Alters Hepatic Wound Healing after Acute Carbon Tetrachloride Exposure in Mice.
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DOI：
10.3390/biom6010005
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发表时间：
2016-01-06
期刊：
影响因子：
5.5
通讯作者：
Pritchard MT
中科院分区：
文献类型：
--
作者：
Deshpande KT;Liu S;McCracken JM;Jiang L;Gaw TE;Kaydo LN;Richard ZC;O'Neil MF;Pritchard MT
伤口愈合包括三个相互重叠的阶段：炎症、增殖、基质合成和重塑。长期酗酒会由于基质重构失控而导致肝纤维化。先前的研究表明，适度的酒精喂养可提高肝纤维化标志物和肝纤维化程度，且与CCl4诱导的肝损伤的差异无关。我们的目标是确定在接触CCl4后，适度乙醇是否会影响肝脏伤口愈合反应的其他阶段。小鼠给予适量乙醇(2%v/v)两天后，暴露于CCl4中，24~96h后处死。肝脏损伤在配对喂养和酒精喂养的小鼠之间没有区别；然而，在酒精喂养的小鼠中，CCl4诱导的肝脏损伤后，坏死组织的清除被推迟。以肿瘤坏死因子Ly6c基因和蛋白及肝脏α转录积累量为指标的炎症反应在酒精喂养后减轻，并与促进肝细胞凋亡有关。在CCl4暴露后，成对喂养和酒精喂养的小鼠的肝细胞同等进入细胞周期，但乙醇喂养的小鼠的肝脏肝细胞增殖延长。与对照组相比，CCl4诱导的肝星状细胞活化增加，基质重塑延长。总而言之，适量的乙醇影响了伤口愈合对CCl4的反应的各个阶段。这些数据突显了先前未知的中度酒精暴露对急性肝毒物质暴露后肝脏伤口愈合的影响。
Wound healing consists of three overlapping phases: inflammation, proliferation, and matrix synthesis and remodeling. Prolonged alcohol abuse can cause liver fibrosis due to deregulated matrix remodeling. Previous studies demonstrated that moderate ethanol feeding enhances liver fibrogenic markers and frank fibrosis independent of differences in CCl4-induced liver injury. Our objective was to determine whether or not other phases of the hepatic wound healing response were affected by moderate ethanol after CCl4 exposure. Mice were fed moderate ethanol (2% v/v) for two days and then were exposed to CCl4 and euthanized 24–96 h later. Liver injury was not different between pair- and ethanol-fed mice; however, removal of necrotic tissue was delayed after CCl4-induced liver injury in ethanol-fed mice. Inflammation, measured by TNFα mRNA and protein and hepatic Ly6c transcript accumulation, was reduced and associated with enhanced hepatocyte apoptosis after ethanol feeding. Hepatocytes entered the cell cycle equivalently in pair- and ethanol-fed mice after CCl4 exposure, but hepatocyte proliferation was prolonged in livers from ethanol-fed mice. CCl4-induced hepatic stellate cell activation was increased and matrix remodeling was prolonged in ethanol-fed mice compared to controls. Taken together, moderate ethanol affected each phase of the wound healing response to CCl4. These data highlight previously unknown effects of moderate ethanol exposure on hepatic wound healing after acute hepatotoxicant exposure.