丹参酮Ⅰ对内毒素脂多糖激活巨噬细胞释放HMGB1的影响

Effect of Tanshinone Ⅰ on HMGB1 Release from Lipopolysaccharide-Stimulated Macrophages

目的研究丹参酮Ⅰ对内毒素脂多糖(LPS)激活后巨噬细胞高迁移率族蛋白B1(HMGB1)释放和脓毒症小鼠血清HMGB1水平的影响。方法以100μg.L-1LPS激活培养巨噬细胞株RAW264.7和小鼠腹腔巨噬细胞,然后观察3.6～18.0μmol.L-1丹参酮Ⅰ对两种巨噬细胞HMGB1释放和巨噬细胞株RAW264.7HMGB1基因表达的影响。以盲肠结扎穿孔术建立脓毒症小鼠模型,观察丹参酮Ⅰ对术后不同时间脓毒症小鼠血清HMGB1水平和存活率的影响。结果丹参酮Ⅰ明显抑制LPS激活后巨噬细胞HMGB1的释放和HMGB1mRNA的表达,降低脓毒症小鼠血清HMGB1水平并明显提高存活率。结论丹参酮Ⅰ有抑制巨噬细胞释放HMGB1和保护脓毒症小鼠作用。

OBJECTIVE To study the effects of tanshinone Ⅰ on extracellular release of high mobility group box protein 1（HMGB1）from lipopolysaccharide-stimulated macrophages and serum HMGB1 level of spesis mice.METHODS The effects of tanshinone Ⅰ（3.6-18.0 μmol·L^-1）were observed on HMGB1 release in cultured macrophage-like RAW 264.7 cells and mouse peritoneal macrophages,and on expression of HMGB1 mRNA in cultured macrophage-like RAW 264.7 cells,after these macrophages were stimulated with 100 μg·L^-1 LPS.The effects of tanshinone Ⅰ were also investigated on serum HMGB1 level and survival rate of spesis mice which were established using cecal ligation and puncture.RESULTS Tanshinone Ⅰ markedly suppressed the release of HMGB1 from LPS-stimulated macrophage-like RAW 264.7 cells and mouse peritoneal macrophages,and the expression of HMGB1 mRNA in LPS-stimulated macrophage-like RAW 264.7 cells.Tanshinone Ⅰ also significantly decreaseed serum HMGB1 level and elevated survival rate of spesis mice.CONCLUSION Tanshinone Ⅰ suppresses extracellular release of HMGB1,and confers protection against sepsis lethality.