HSF1基因剔除对HSR抗内毒素血症的影响  

Role of HSF1 Knock-out in Protection of Heat Shock Response Against Endotoxemia

作　　者：陈广文[1] 王慷慨[1] 刘瑛[1] 唐道林[1] 肖献忠[1] 

机构地区：[1]中南大学湘雅医学院病理生理学系,长沙410078

出　　处：《生物化学与生物物理进展》2008年第4期424-430,共7页Progress In Biochemistry and Biophysics

基　　金：国家重点基础研究发展规划项目(973)(2007CB512007);国家自然科学基金重点资助项目(30330280)~~

摘　　要：利用内毒素(LPS)血症小鼠模型,观察HSF1基因剔除对热休克反应(HSR)保护作用的影响.采用腹腔注射LPS建立内毒素血症小鼠模型,HSR采用肛温42℃维持15min,室温恢复24h,利用RT-PCR、苏木素-伊红(HE)染色、丙二醛测定以及死亡率,计算和分析重要脏器组织中炎症介质基因的表达、脏器损伤程度及小鼠存活率.注射LPS15mg/kg72h后HSR+LPS(HSF1+/+)组存活率(7/15)显著高于LPS(HSF1+/+)组(0/15)、LPS(HSF1-/-)组(0/14)和HSR+LPS(HSF1-/-)组(0/14),而注射LPS14mg/kg72h后,LPS(HSF1+/+)组存活率(5/15)显著高于LPS(HSF1-/-)组(0/13)和HSR+LPS(HSF1-/-)组(0/13).在注射LPS12h后LPS(HSF1+/+)组、LPS(HSF1-/-)组和HSR+LPS(HSF1-/-)组的心、肺组织丙二醛含量显著升高,但HSR+LPS(HSF1+/+)组不升高.肺组织炎症介质基因IL-1β、IL-6、TNF-α、CCL-2、SOCS3、MCSF、GCSF、IL-15在LPS(HSF1-/-)组和LPS(HSF1+/+)组表达上调,HSR+LPS(HSF1-/-)组除IL-15较低外其他上调更甚,HSR+LPS(HSF1+/+)组除IL-1β和TNF-α较高外其他显著下调.注射LPS后LPS(HSF1+/+)组和LPS(HSF1-/-)组的肺、肝、肾病理形态改变明显,HSR+LPS(HSF1+/+)组改变较轻,HSR+LPS(HSF1-/-)组改变更加严重.HSF1基因剔除能显著消减HSR对内毒素血症小鼠的保护作用.Using LPS mediated-endotoxemia BalB/C mice, the role of heat shock factor 1 （HSF1） in heat shock response （HSR） was observed. HSR was performed with 42℃ for 15 min, and recovery for 24 h at room temperature. Endotoxemia model in mouse was achieved by intra-peritoneal injection of LPS at 14 or 15 mg/kg. Lung injury and expression of inflammatory mediators were evaluated with myeloperoxidase （MPO） and maleic dialdehyde （MDA） in heart and lung, RT-PCR, hemotoxylin-eosin （HE） staining and mortality. The data showed that the survival rate was higher in HSR＋LPS （HSF1＋/＋） group （7/15） than that in LPS （HSF1＋/＋） group （0/15）, LPS （HSF1-/-） group （0/14） or HSR＋LPS （HSF1-/-） group （0/14） within 72 h after injection of LPS at 15 mg/kg. Similarly, the survival rate was also higher in LPS （HSF1＋/＋） group （5/15） than that in LPS （HSF1-/-） group （0/13） or HSR＋LPS （HSF1-/-） group （0/13） within 72 h after injection of LPS at 14 mg/kg. HSR significantly suppressed production of MPO and MDA induced by LPS in lung and heart in HSF1＋/＋ mice, but had no such effects in HSF1-/- mice after 12 h treatment with 14 mg/kg LPS. The inflammatory mediators, including SOCS3, MCSF, GCSF, IL-1β, IL-6, CCL-2 and IL-15 were up-regulated both in HSF1＋/＋ and HSF1-/- mice after12 h treatment with LPS at 14 mg/kg, and HSR repressed LPS-induced up-regulation of SOCS3, MCSF, GCSF, IL-15, IL-6 and of CCL-2 in HSF1＋/＋ mice, but not in HSF1-/- mice. HE staining indicated that LPS at 14 mg/kg could mediate significant morphological changes, including necrosis, intravascular coagulation and leukocytes aggregation, and adherence in lung, liver and kidney in HSF1＋/＋ and HSF1-/- mice. The morphological changes in these organs were attenuated with HSR in HSF1＋/＋ mice, but exacerbated in HSF1-/- mice. Those results suggested that HSF1 knock out could significantly block the protection of HSR against LPS mediated-endotoxemia in BalB/C mice.

关 键 词：热休克反应 内毒素血症 基因剔除 热休克因子1 炎症介质 

分 类 号：R361.1[医药卫生—病理学]