Protective effects of nafamostat mesilate on liver injury induced by lipopolysaccharide in rats: Possible involvement of CD14 and TLR-4 downregulation on Kupffer cells
Protective effects of nafamostat mesilate on liver injury induced by lipopolysaccharide in rats: Possible involvement of CD14 and TLR-4 downregulation on Kupffer cells
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DOI：
10.1007/s10620-006-9141-1
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发表时间：
2006-11-01
影响因子：
3.1
通讯作者：
Iwagaki, Hiromi
中科院分区：
文献类型：
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作者：
Miyaso, Hideaki;Morimoto, Yoshinori;Iwagaki, Hiromi
甲磺酸萘莫司他（NM）是一种人工合成的蛋白酶抑制剂，具有多种生物学效应。为了确定其对脓毒症相关肝损伤的影响，我们研究了NM对脂多糖（LPS）诱导的肝损伤的影响。将Wistar大鼠分为两组，NM组在LPS给药前30 min腹腔注射NM，对照组注射PBS。NM治疗组大鼠血清AST和ALT水平显著降低。在NM处理的大鼠中，LPS给药后观察到TNF-α、IL-1 β和IFN-γ水平降低。NM组和对照组之间的IL-6水平无显著差异。与此相反，HGF水平显着增加，只有在对照组大鼠。NM处理降低TLR-4和CD 14的蛋白和mRNA水平。我们的数据表明，NM治疗通过下调肝脏中的TLR 4和CD 14，降低肝脏中TNF-α，IL-1 β和IFN-γ的产生，对LPS诱导的肝毒性具有保护作用。
Nafamostat mesilate (NM) is a synthetic protease inhibitor with various biological effects. To determine its effect on liver injury related to sepsis, we investigated the effects of NM on lipopolysaccharide (LPS)-induced liver injury. Wistar rats were allocated into two groups; the NM group underwent intraperitoneal NM administration 30 min before LPS administration, and the control group underwent PBS administration. Serum AST and ALT levels were significantly decreased in NM-treated rats. Reduced levels of TNF-alpha, IL-1 beta, and IFN-gamma were observed after LPS administration in NM-treated rats. No significant differences were observed in IL-6 levels between the NM and the control group. In contrast, HGF levels were significantly increased only in control rats. NM treatment decreased protein and mRNA levels of TLR-4 and CD14. Our data suggest that NM treatment has protective effects against LPS-induced hepatotoxicity through downregulation of TLR4 and CD14 in liver, which decreased TNF-alpha, IL-1 beta, and IFN-gamma production in liver.