烧伤并发内毒素血症早期肝损害与TNF-α mRNA表达的实验研究

目的观察 TNF-α mRNA 及其蛋白的组织分布和细胞定位,探讨烧伤并发内毒素血症早期肝损害的发生机理。方法选用20%Ⅲ度 TBSA 烧伤大鼠合并腹腔内毒素(LPS)注射造成烧伤复合内毒素血症肝损害模型,采用光镜,电镜及免疫组化原位杂交染色观察大鼠肝脏的形态功能变化、血清 TNF-α含量变化、肝组织 TNF-α和 TNF-α mRNA 的细胞定位及其分布。结果烧伤复合内毒素血症组,光镜下主要表现肝窦反应,枯否细胞(KCs)激活与增生以及肝细胞(HCs)变性坏死等;电镜下主要表现肝窦内血小板聚集、纤维素沉积与中性粒细胞(PMNs)扣押以及 KC_s、肝细胞退变溶解等。血清丙氨酸氨基转氯酶(ALT)显著升高(P<0.01)和白蛋白(ALB)轻度下降。组织TNF-α主要定位于肝窦内皮细胞(SECs)、KCs。TNF-α mRNA 主要定位于 KCs、PMNs、巨噬细胞(MPs)。而在单因素组主要特点为病变程度轻,肝功能损害不明显,血清 TNF-α峰值滞后以及组织TNF-α和 TNF-α mRNA 表达相对较弱等。结论 TNF-α是参与烧伤复合内毒素血症早期肝脏损害的重要细胞因子。     

烧伤并发内毒素血症早期肝损害与TNF-α mRNA表达的实验研究

目的观察ＴＮＦαｍＲＮＡ及其蛋白的组织分布和细胞定位,探讨烧伤并发内毒素血症早期肝损害的发生机理。方法选用２０％Ⅲ度ＴＢＳＡ烧伤大鼠合并腹腔内毒素（ＬＰＳ）注射造成烧伤复合内毒素血症肝损害模型,采用光镜,电镜及免疫组化原位杂交染色观察大鼠肝脏的形态功能变化、血清ＴＮＦα含量变化、肝组织ＴＮＦα和ＴＮＦαｍＲＮＡ的细胞定位及其分布。结果烧伤复合内毒素血症组,光镜下主要表现肝窦反应,枯否细胞（ＫＣｓ）激活与增生以及肝细胞（ＨＣｓ）变性坏死等;电镜下主要表现肝窦内血小板聚集、纤维素沉积与中性粒细胞（ＰＭＮｓ）扣押以及ＫＣｓ、肝细胞退变溶解等。血清丙氨酸氨基转氨酶（ＡＬＴ）显著升高（Ｐ＜０．０１）和白蛋白（ＡＬＢ）轻度下降。组织ＴＮＦα主要定位于肝窦内皮细胞（ＳＥＣｓ）、ＫＣｓ。ＴＮＦαｍＲＮＡ主要定位于ＫＣｓ、ＰＭＮｓ、巨噬细胞（ＭＰｓ）。而在单因素组主要特点为病变程度轻,肝功能损害不明显,血清ＴＮＦα峰值滞后以及组织ＴＮＦα和ＴＮＦαｍＲＮＡ表达相对较弱等。结论ＴＮＦα是参与烧伤复合内毒素血症早期肝脏损害的重要细胞因子。     

内毒素血症时肝组织中脂多糖受体CD14的表达及其意义

目的 观测内毒素血症时大鼠肝组织中脂多糖受体CD14 mRNA的表达及其在内毒素介导Kupffer细胞（KCs)激活中的作用。方法 经大鼠尾静脉注入内毒素（剂量按5mg/kg计算）建立内毒素血症动物模型，测定血浆中内毒素、脂多糖结合蛋白（LBP)、TNF－α及IL－6含量变化，同时观测不同时相点肝组织中CD14 mRNA的表达及肝组织形态学变化，并与生理盐水组大鼠相比较。结果 在内毒素血症组大鼠中，随着血浆LPS浓度升高和时间延长，肝组织中CD14 mRNA的表达明显增强；血浆中LBP、TNF－α和IL－6含量也明显增加，与对照组相比较有显著差异（P＜0．01）。伴随KCs激活和肝细胞损伤的形态学改变，表现为KCs数量增多、体积增大、噬功能增强，肝细胞出现变性、坏死等变化。结论 内毒素血症时，随着肝组织中CD14表达增强和血浆LBP增加，可介导KCs激活，产生和释放多种细胞因子，诱导或加重肝组织及其它器官的损害。     

烧伤合并内毒素血症TNFαmRNA原位表达与早期心肌损害的实验研究

目的观察TNFαmRNA及其蛋白在心肌细胞的原位表达,探讨烧伤合并内毒素血症早期心肌损害的可能机制。方法采用20％TBSAⅢ度烧伤复合内毒素血症多脏器损害模型,时相点设为伤后0.5、1、3、6、12、24和48h。将178只大鼠随机分为烧伤复合内毒素注射组(烧注组)、单纯烧伤(单烧组)、单纯内毒素注射组(单注组)和正常对照组。采用光、电镜观察,ELISA及免疫组化,原位杂交染色,等观察大鼠心肌形态功能变化、血清TNFα含量变化、TNFαmRNA及其蛋白在心肌细胞的定位及分布。结果烧注组致伤早期心肌出现一系列损害性改变,如波浪变性、收缩带形成、肌纤维断裂和灶性胞浆内溶解等。左室收缩压(LVSP)及室内压最大变化速率(±dp/dtmax)显著下降(P＜0.01)。血清TNFα水平于1h明显升高(P＜0.01),3～6h达高峰。TNFαmRNA主要定位于心肌细胞和部分炎细胞。而单因素组病变程度轻,心肌损害不明显,血清TNFα峰值滞后以及心肌组织TNFαmRNA表达相对较弱。结论烧伤合并内毒素血症状态下,心肌本身可表达TNFαmRNA及其蛋白,并可能作为机体TNFα产生来源之一,参与早期心肌结构与功能损害的发生发展。     

烧伤复合内毒素血症对肝脏的损害及其意义的研究

２０％ＩＩＩ度体表烧伤复合１μｇ／ｇ内毒素注射对大鼠肝脏的损害显示明显的协同效应。其病变过程可分为肝窦反应与枯否氏细胞增生期，肝细胞与枯否氏细胞变性坏死期和损伤修复期三个阶段。根据病理组织学，酶细胞化学和超微结构变化观察，结合血浆内毒素检测，电镜立体形态计量分析和肝功能变化等结果，提示细菌内毒素在烧伤早期肝脏损害发生机制中具有重要的致病作用。文中重要计论了烧伤状态下，内毒素对肝脏的损害效应，病变特     

TNFα、NO在烧伤复合内毒素血症早期肾损害中的作用及其意义

目的 探讨肿瘤坏死因子α(TNFα)、一氧化氮(NO)在烧伤合并内毒素血症早期肾脏损害中的作用及其意义。方法 以大鼠体表烧伤Ⅲ度20％TBSA合并小剂量内毒素(1mg／kg体重)腹腔注射造成多脏器损害模型,按设计分组并在致伤后不同时相点进行肾脏病理形态学观察、TNFα和NO血清浓度测定、TNFα mRNA原位杂交和iNOS免疫组化染色。结果 烧伤后注射内毒素组诱导型一氧化氮合酶(iNOS)的表达和NO的合成以及TNFα mRNA的表达和TNFα的血浆水平均显高于和早于单纯烧伤组和单纯注射内毒素组。结论 烧伤合并内毒素血症时肾组织中NO和TNFα的水平显升高,两的升高可能是导致肾脏损害和引起肾脏血流动力学改变的重要因素之一。     

烧伤复合内毒素血症对肝脏的损害及其意义的研究

20％Ⅲ度体表烧伤复合lμg/g内毒素注射对大鼠肝脏的损害显示明显的协同效应。其病变过程可分为肝窦反应与枯否氏细胞增生期、肝细胞与枯否氏细胞变性坏死期和损伤修复期三个阶段。根据病理组织学、酶细胞化学和超微结构变化观察,结合血浆内毒素检测、电镜立体形态计量分析和肝功能变化等结果,提示细菌内毒素在烧伤早期肝脏损害发生机制中具有重要的致病作用。文中重点讨论了烧伤状态下,内毒素对肝脏的损害效应、病变特点、演变规律及其形态发生机制。     

烧伤复合内毒素血症对肝脏的损害及其意义的研究

２０％Ⅲ度体表烧伤复合１μｇ／ｇ内毒素注射对大鼠肝脏的损害显示明显的协同效应。其病变过程可分为肝窦反应与枯否氏细胞增生期、肝细胞与枯否氏细胞变性坏死期和损伤修复期三个阶段。根据病理组织学、酶细胞化学和超微结构变化观察，结合血浆内毒素检测、电镜立体形态计量分析和肝功能变化等结果，提示细菌内毒素在烧伤早期肝脏损害发生机制中具有重要的致病作用。文中重点讨论了烧伤状态下，内毒素对肝脏的损害效应、病变特点、演变规律及其形态发生机制。     

枯否细胞NF-κB 激活对胆源性内毒素血症大鼠肝部分切除后肝细胞再生的影响

目的探讨胆源性内毒素血症(BE)大鼠肝部分切除(PH)后枯否细胞(KCs)核因子-κB(NF-κB))激活对肝细胞再生的影响.方法将Wistar大鼠分为4组(每组72只)N-PH组(正常大鼠70%PH组);BE-PH组(BE大鼠70%PH组);BE-PH 白细胞介素(IL)-10治疗组;BE-PH治疗对照组.检测70%PH后0、1、6、24、48、72h KCs NF-κB 激活、KCs肿瘤坏死因子α(TNFα)mRNA、IL-1βmRNA和IL-6 mRNA表达以及肝细胞溴脱氧核苷尿嘧啶(BrdU)标记.结果 BE-PH组KCs NF-κB活性高于N-PH组(P<0.001),KCs TNFαmRNA、IL-1βmRNA及IL-6 mRNA表达亦明显高于N-PH组,而肝细胞BrdU高峰标记指数(38.82±9.79)低于N-PH组(64.37±13.69)(P<0.01);BE-PHIL-10组KCs NF-κB 活性低于BE-PH组(P<0.01),KCs TNFα、IL-1β及IL-6 mRNA表达减少,而肝细胞BrdU高峰标记指数高于BE-PH组(P<0.05).结论 BE-PH后KCs NF-κB 高水平激活导致KCs TNFαmRNA、IL-1βmRNA及IL-6 mRNA表达增高,从而抑制肝细胞再生,适当调控KCs NF-κB 活性能促进BE-PH后肝细胞再生.     

重组人生长激素对大鼠肝脏缺血再灌注损伤的保护作用

目的 探讨重组人生长激素（rhGH）对肝脏缺血再灌注损伤的保护作用及其机理。方法 Pringle法建立100只肝脏缺血再灌注损伤动物模型，rhGH组于建立模型前7d每天给予rhGH针剂皮下注射（0．2U／100g体重），对照组等量生理盐水注射，观察其血清ALT、TNFα和IL-1a的变化，检测肝细胞中丙二醛（MDA）、肝脏能荷（energy charge，EC）的变化及核转录因子-kB（NF—kB）和细胞间黏附分子-1（ICAM-1）mRNA的表达，电镜观察肝脏的超微结构变化。结果 rhGH组ALT、TNFα、IL-1a和MDA在各个时间点的水平均明显低于对照组（P〈0．05），rhGH组EC水平明显高于对照组（P〈0．05）；rhGH组肝细胞核因子NF—kB表达及ICAM1mRNA的表达水平均明显低于对照组（P〈0．05）。对照组电镜下可见肝窦内皮细胞破坏，肝细胞线粒体结构改变，rhGH组肝细胞超微结构明显改善。结论 rhGH可能通过下调NF-kB的表达，进一步抑制了细胞因子（TNF—α、IL-1α）和ICAM1致炎因子mRNA的表达，减少MDA的生成，从而减轻了这些因子对肝脏的损伤。     

p38丝裂原活化蛋白激酶信号转导通路在严重烧伤大鼠枯否细胞肿瘤坏死因子α和白细胞介素1β产生中的作用

目的 探讨p38丝裂原活化蛋白激酶(MAPK)信号转导通路在严重烧伤大鼠枯否细胞(KCs)促炎性细胞因子肿瘤坏死因子α(TNF-α)和白细胞介素1β(IL-1β)产生中的作用。方法 健康成年的雄性SD大鼠32只,随机分为：假烫组;假烫 SB203580组;烧伤对照组;烧伤 SB203580组,每组8只。假烫或烧伤24h后分离出肝脏KCs,培养18h后加入50ng／ml的LPS进行刺激,18h后取上清液,用酶联免疫吸附法(ELISA)测定TNF-α和IL-1β的含量,并收集KCs,实时逆转录聚合酶链反应检测KCs内TNF-α和IL-1β mRNA表达的改变,蛋白印迹(Western blot)法检测KCs中p38MAPK和JNK活性的变化。结果 烧伤大鼠分离出的KCs培养上清液中TNF-α和IL-1β含量、KCs中TNF-α和IL-1β mRNA的表达均较假烫组的明显增强,同时KCs中p38 MAPK活性和JNK活性升高,SB203580能显著抑制大鼠KCs上清液中TNF-α和IL-1β含量、KCs中TNF-α和IL-1β mRNA的表达和p38MAPK活性的升高,对JNK活性无影响。结论p38MAPK信号转导通路介导了严重烧伤大鼠KCs促炎性细胞因子TNF-α和IL-1β的产生。     

Lipopolysaccharide-binding protein and lipopolysaccharide receptor CD14 gene expression after thermal injury and its potential mechanism(s)

BACKGROUND: We hypothesized that lipopolysaccharide-binding protein (LBP) and lipopolysaccharide receptor CD14 would present a pair of key molecules in pathophysiologic alterations induced by low concentrations of endotoxin after trauma. The aim of this study was to investigate the relationship between endotoxin translocation and tissue LBP/CD14 messenger ribonucleic acid (mRNA) expression after burn injury, and to define the potential role of LBP/CD14 in mediating inflammatory mediator induction, as well as the pathogenesis of organ damage. METHODS: Wistar rats were subjected to a 35% full-thickness scald injury, and tissue samples from liver, kidneys, lungs, and intestine were collected to measure LBP/CD14 and tumor necrosis factor-alpha (TNF-alpha) mRNA expression. Peritoneal macrophages were harvested by peritoneal lavage to determine CD14 mRNA expression. RESULTS: It was found that endotoxin levels in liver, spleen, and lung increased markedly after thermal injury, with the highest level in liver. Both tissue LBP and CD14 mRNA expression increased markedly after burns, peaking at 12 hours, and then decreasing gradually. At 48 hours, LBP gene expression had a tendency to the baseline level, whereas CD14 mRNA expression increased again. Likewise, CD14 mRNA levels were up-regulated markedly in peritoneal macrophages. Conversely, gene expression of TNF-alpha in tissues elevated markedly after acute insults. There were positive correlations between lipopolysaccharide levels and LBP/CD14 mRNA as well as TNF-alpha mRNA expression in tissues. Similar results were also obtained between CD14, TNF-alpha mRNA expression in liver tissue and liver function parameters, and between pulmonary TNF-alpha mRNA and myeloperoxidase activities (p < 0.01). CONCLUSION: Thermal injury per se can markedly up-regulate both LBP and CD14 gene expression in various organs. Excessive LBP and CD14 mRNA expression might be associated with enhanced synthesis and release of TNF-alpha stimulated by endotoxin translocation after major burns.     

休克期切痂对烫伤大鼠肝、肺组织高迁移率族蛋白B1表达及促炎/抗炎平衡的影响

目的 观察休克期切痂对烫伤大鼠组织早期和晚期炎症介质变化规律及相应器官功能的影响,探讨休克期切痂改善预后的分子机制。方法 Wistai大鼠30％Ⅲ度烫伤后随机分为24h切痂组和72h切痂组。分别检测肝、肺组织高迁移率族蛋白B1(HMGB1)、白介素-10(IL-10)及肿瘤坏死因子-α(TNF-α)的表达。结果烫伤后2d,肝、肺组织HMGB1、TNF-α mRNA表达增强,而IL-10mRNA伤后8d增强;24h切痂大鼠伤后4d肝、肺组织HMGB1和TNF-α mRNA表达下调,伤后8d其IL-10 mRNA表达恢复正常;72h切痂大鼠伤后8d肝、肺IL-10mRNA仍维持较高水平。伤后2．8d肝组织内TNF-α蛋白水平呈双峰改变,4d时减少;24h和72h切痂组肝TNF-α维持在正常范围;伤后2、4d肝TNF-α／IL-10比例升高,24h切痂可降低TNF-α／IL-10。此外,24h切痂组4、8d血浆天冬氨酸氨基转移酶和丙氨酸氨基转移酶含量及肺组织髓过氧化物酶活性显著降低。结论休克期切痂可阻断严重烫伤大鼠肝、肺组织早期和晚期炎症介质过度表达,维持促炎／抗炎介质平衡,改善多脏器功能。     

Decreased wound neutrophils and indiscrete margination in the pathogenesis of wound infection

To assess the pathogenesis of increased susceptibility to infection and septic death in a rat model, neutrophils (PMNs) in the wound, circulating PMNs, and their in vivo activity were evaluated after 30% and 60% burns. Eight hours after injury there were twice as many PMNs in the wounds of rats that sustained 30% compared with 60% burns. There was no difference between these two groups in the number of circulating PMNs at 2, 4, 6, and 8 hours after injury. In vivo evaluation of PMN response to infusion of F-Met-Leu-Phe revealed that circulating PMNs were more sensitive 4 hours after 60% burns compared with sham burns. At this time PMNs were found to be less sensitive to zymosan-activated serum infusion after 30% burns compared with sham burns. However, the PMNs in rats with 30% burns were more sensitive to this stimulus than were PMNs in rats with 60% injuries. Thus rats with greater injury, known to be more susceptible to wound infection, have fewer PMNs in their wounds 8 hours after injury. This is preceded by an increased sensitivity of PMNs in vivo to bacterial chemotactic factor and a relative increase in sensitivity to wound factors. This unusual finding implicates indiscrete margination as a factor in the pathogenesis of infection.     

p38 mitogen-activated protein kinase inhibition attenuates burn-induced liver injury in rats

This study was made to evaluate the effect of SB203580, a specific p38 MAP kinase inhibitor, on burn-induced hepatic injury as well as the activation of nuclear factor (NF)-kappaB in severely burned rats. Sprague-Dawley rats were divided into three groups: (1) sham group, rats underwent sham burn; (2) burn group, rats given third-degree burns over 30% total body surface area (TBSA) and treated with vehicle plus lactated Ringer solution for resuscitation 4 ml/(kg% TBSA); and (3) burn plus SB203580 group, rats given burn injury and fluid resuscitation plus SB203580 (10 mg/kg i.v., 15 min and 12 h after burn). Hepatocellular injury (measured by serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT)) and hepatocellular function (determined by the indocyanine green dye retention rate (ICG R15)) were assessed at 24 h post-burn. Liver histologic changes were also analyzed. Burn trauma resulted in increased serum aminotransferases concentrations, decreased ICG R15, elevated serum tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta levels and hepatic TNF-alpha and IL-1beta mRNA expressions, and worsen histologic condition. The level of Nuclear Factor (kappa) inhibitor (IkappaBalpha) in liver was decreased and DNA-binding activity of Nuclear Factor-kappaB (NF-kappaB) was increased after thermal injury. p38 MAP kinase was more significantly activated in liver harvested from burn rats than from shams. SB203580 inhibited the activation of p38 MAP kinase, reduced the levels of TNF-alpha and IL-1beta, and prevented burn-mediated liver injury. Both the IkappaBalpha level and NF-kappaB activity in the liver following burns was not affected by administration with SB203580. These findings suggest that (1) p38 MAP kinase activation is one important aspect of the signaling event that may mediate the release of TNF-alpha and IL-1beta and contributes to burn-induced liver injury and (2) p38 MAP kinase does not influence the activation of NF-kappaB directly in the liver of severely burned rats.     

烫伤大鼠组织肿瘤坏死因子mRNA表达与内毒素血症的关系

目的 探讨烫伤后不同组织肿瘤坏死因子（ＴＮＦ－α）ｍＲＮＡ的动态表达及其与内毒素血症的关系。方法 采用大鼠３５％体表面积Ⅲ度烫伤模型,实验随机分为正常对照组、烫伤组、多粘菌素Ｂ治疗组。血浆内毒素水平采用改良过氯酸预处理血浆偶氮显色法鲎试验定量测定;组织ＴＮＦ－αｍＲＮＡ含量采用逆转录聚合酶链反应检测。结果 烫伤后门静脉及体循环内毒素水平均显著升高,８ｈ达高峰,２４ｈ则逐渐下降。给予低剂量多粘菌素Ｂ     

Role of Kupffer cells in lung injury in rats administered endotoxin 1

The purpose of this study was to investigate the regulation of lung macrophages (Muvarphis) by Kupffer cells (KCs) in lung injury caused by endotoxemia. Phenotypic differences in tissue Muvarphis were also investigated. Muvarphis were isolated from gadolinium chloride (GdCl(3))- or saline-treated rats 2 h after saline or lipopolysaccharide (LPS) administration. Furthermore, rats were given GdCl(3) 24 h prior to LPS administration, and survival rate was assessed for 24 h. Moreover, lung edema was assessed 9 h after LPS injection. Expression of inflammatory mediators was measured in the liver and lung. KCs were divided into three subpopulations based on size and phagocytosis. The expression of TNF-alpha and MIP-2 was greater in the small KCs and lung Muvarphis, while the expression of IL-6, IL-10, and MCP-1 was greater in the large and intermediate KCs. GdCl(3) eliminated ED2-positive large KCs and did not have any effect on the lung Muvarphis. The number of ED1-positive KCs increased significantly in both organs after LPS challenge and was reduced by GdCl(3). The population of ED2-positive KCs did not change following LPS administration. GdCl(3) completely prevented increases in lung microvascular permeability and mortality after LPS infusion. After LPS administration, expression of TNF-alpha and IL-6 increased rapidly and then decreased gradually in both organs. GdCl(3) inhibited these increases in the liver significantly and enhanced the expression of MCP-1 and IL-10 in the lung 9 h after LPS administration. Thus, the heterogeneous response of KCs to endotoxin leads to production of certain cytokines and chemokines that affect lung function.     

Glycine attenuates endotoxin-induced liver injury by downregulating TLR4 signaling in Kupffer cells

BACKGROUND: Several experimental studies have observed better outcomes after glycine treatment in patients with endotoxin-induced liver injuries, but its molecular mechanism is not yet fully understood. The purpose of this study was to evaluate the hypothesis that glycine attenuates endotoxin-induced liver injury by affecting endotoxin signal transduction in liver macrophages. METHODS: An animal model of endotoxin-induced liver injury was established by intraperitoneally injecting mice with 10 mg/kg body weight endotoxin fed a pretreatment diet with or without 5% (w/w) glycine. Blood and liver samples were obtained for analysis of liver morphology and to determine concentrations of alanine aminotransferase, endotoxin receptor Toll-like receptor 4 (TLR4), tumor necrosis factor-alpha (TNF-alpha), and interleukin (IL)-10 at various time points after injection. To investigate the effect of glycine on liver macrophages, Kupffer cells (KCs) were isolated and challenged by LPS (100 ng/mL), with or without glycine (4 mmol/l) pretreatment, and the expressions of TLR4, IL-10, and TNF-alpha were assayed at mRNA and protein levels. DNA-binding activity of nuclear factor-kappa B (NF-kappaB) was also analyzed using enzyme-linked immunosorbent assay. RESULTS: Dietary glycine significantly improved the survival rate of endotoxemic mice (P < .05), whereas serum alanine aminotransferase and TNF-alpha levels were significantly decreased at different time points (P < .05); IL-10 levels were increased (P < .05). Concurrently, LPS-induced hepatic tissue injury was attenuated as indicated by morphologic analysis; secretion of IL-10 in liver tissue (P < .05) was enhanced; and expression of TLR4 and TNF-alpha in liver tissue was downregulated (P < .05). Consistent with these in vivo experiments, enhanced secretion of IL-10 and inhibited expression of TLR4 and TNF-alpha caused by glycine pretreatment were also observed in LPS-stimulated KCs. NF-kappaB DNA-binding activity was also significantly inhibited by glycine (P < .05, respectively). CONCLUSIONS: Dietary glycine improved survival rates and liver function in endotoxemic mice by regulating the production of proinflammatory or anti-inflammatory cytokines in liver. It attenuated liver injury by deactivating KCs through inhibiting TNF-alpha secretion and increasing IL-10 production. The downregulative effect of glycine on the endotoxin signaling pathway and TLR4/NF-kappaB/TNF-alpha may be a novel potential mechanism by which glycine inhibits KC activity.     

严重烫伤后高迁移率族蛋白-1基因表达的改变及意义

目的　观察烫伤后肝、肺组织高迁移率族蛋白-1（HMG-1）mRNA表达的变化规律及其与器官功能损害的关系。　方法　采用大鼠35%Ⅲ度烫伤模型,动物随机分为正常对照组、烫伤组和重组杀菌/通透性增加蛋白(rBPI21)治疗组,留取组织和血标本分别检测组织内毒素含量、HMG-1mRNA表达及器官功能指标。　结果　严重烫伤后早期肝、肺组织HMG-1基因表达改变不明显（正常对照组肝组织0.202±0.097;肺组织0.263±0.091）,伤后24h则明显增多(肝组织0.487±0.189;肺组织0.513±0.069,P＜0.05,0.01),且一直持续至伤后72h(肝组织0.687±0.142;肺组织0.520±0.076,P＜0.01)。给予rBPI21治疗可有效抑制肝和肺中内毒素水平的升高,并显著抑制肝、肺组织HMG-1mRNA水平(P＜0.01)。相关分析结果显示,肝组织HMG-1mRNA表达与血清谷丙转氨酶、谷草转氨酶水平、肺组织HMG-1mRNA表达与髓过氧化物酶活性呈显著正相关（P＜0.05,0.01）。　结论　严重烫伤后肝、肺组织HMG-1表达显著增多,且持续时间较长,局部组织HMG-1诱生与烧伤后内毒素介导的重要器官功能损害关系密切。