大鼠失血性休克对内毒素诱导TNFα产生的影响及其分子机制

Effect of Hemorrhagic Shock in Rat on Endotoxin induced TNFα Production and its Molecular Mechanism

笔者观察了大鼠失血性休克（ＨＳ）对内毒素诱导肿瘤坏死因子α（ＴＮＦα）产生的影响及其细胞来源，并结合休克后组织内脂多糖结合蛋白（ＬＢＰ）ｍＲＮＡ的表达变化，对其分子机制进行了初步分析。研究结果显示，静脉注射ＬＰＳ后９０ｍｉｎ，ＨＳ＋ＬＰＳ组血浆ＴＮＦα水平分别较ＨＳ组高２０倍（Ｐ＜０．０１），ＬＰＳ组高２．７倍（Ｐ＜０．０５）；休克和复苏后，外周血白细胞产生ＴＮＦα的能力明显受抑，而肝Ｋｕｐｆｅｒ＇ｓ细胞产生ＴＮＦα的能力却明显增强；休克后不仅肝组织内ＬＢＰｍＲＮＡ表达增多，肺、肾组织内ＬＢＰｍＲＮＡ也相继表达增加。研究结果提示，失血性休克能显著增敏内毒素诱导ＴＮＦα的产生作用，其机制可能与休克后组织内ＬＢＰ表达上调有关，组织巨噬细胞群（如Ｋｕｐｆｅｒ细胞）可能是休克后细胞因子产生的主要来源。

The present study was designed to investigate the effect of hemorrhagic shock(HS) on endotoxin induced tumor necrosis factor α(TNFα) production and its cellular sources. With combination of expression of lipopolysaccharide binding protein(LBP) mRNA in tissues after shock, we further tentatively analyzed its molecular mechanism. It was found that 90 min after injection of LPS, plasma TNFα levels in HS+LPS group were 20 fold higher than those in HS group(p<0 01),and 2 7 fold higher than those in LPS group(P<0 05);The capacity of the peripheral white blood cells to produce TNFα was significantly decreased, while the capacity of hepatic Kupffer's cells to produce TNFα was significantly increased after shock and resuscitation;Expression of LBP mRNA was markedly increased not only in the liver,but also in the lungs and kidneys after shock.It is suggested that hemorrhagic shock could significantly increase induction of TNFα production by endotoxin,which mechanism might be related to upregulation of LBP expression,tissue macrophage population (such as Kupffer cells) might be the main source for cytokine production in shock.