大黄素对腹腔感染大鼠血浆白蛋白及TNF-α、IL-6影响的实验研究

目的：探讨大黄素对于腹腔感染大鼠的保护作用。方法：90只大鼠随机分为3组，A组：假手术组；B组：大黄素治疗组；C组：盲肠结扎穿孔模型（CLP）组。造模12h，2，4h，36h后分别测定血浆白蛋白浓度、肿瘤坏死因子-α（TNF—α）、白介素-6（IL-6）等并观察肠粘膜损伤程度。结果：CLP后大鼠血浆白蛋白浓度降低，而C组下降较B组明显（P〈0．05）。TNF—α、IL-6明显升高，而C组升高较B组明显（P〈0．01），肠粘膜损伤评分变化也有相同趋势（P〈0．05）。结论：大黄素能减轻CLP所致腹腔感染大鼠的炎症反应和肠粘膜的损伤。     

甲状腺激素对脓毒症大鼠肠粘膜屏障的保护作用

目的 探讨补充外源性甲状腺激素对脓毒症大鼠肠粘膜屏障的保护作用。方法 将ＳＤ大鼠３０只随机分为３组：假手术组、脓毒症组和治疗组。利用盲肠结扎打孔法（ＣＬＰ）制作大鼠脓毒症模型,通过腹腔注入１０ｍｇ／Ｌ三碘甲状腺原氨酸（Ｔ３）１．５ｍｌ／ｋｇ体重,以纠正脓毒症大鼠的低Ｔ３状态,用透射电镜观察肠粘膜机械性屏障的变化。结果 治疗组动物脓毒症表现轻,２４ｈ存活率显著高于脓毒症组（Ｐ〈０．０５）。脓毒症组大     

甲状腺激素对脓毒症大鼠血清一氧化氮浓度及肠粘膜一氧化氮合酶的影响

目的探讨补充外源性甲状腺激素对脓毒症大鼠血清一氧化氮 (NO)及肠粘膜诱导型一氧化氮合酶 (iNOS)的影响。方法应用盲肠结扎打孔法制作大鼠脓毒症模型 ,32只雄性SD大鼠随机分为 4组 :假手术组、脓毒症组、T3预防组及T3治疗组。术后 2 4h检测血清NO及甲状腺激素浓度 ,取末端回肠HE染色以判断组织损伤程度 ,同时应用免疫组化检测小肠粘膜中iNOS的表达。结果T3预防组动物死亡率较脓毒症组低 (LogRank检验值 =3 85 ,P <0 0 5 ) ,血清NO浓度降低 (F =19 6 ,P <0 0 1) ,肠粘膜损伤程度减轻 (χ2 =5 30 3,P <0 0 5 ) ,肠粘膜上皮细胞iNOS的表达明显下降(χ2 =4 876 ,P <0 0 5 )。结论脓毒症时补充外源性甲状腺激素对肠粘膜屏障具有明显的保护作用。     

Toll样受体4介导心肺复苏后肠粘膜损伤的研究

目的探讨Toll样受体4（TLR4）信号在心脏骤停及复苏后肠粘膜损伤中的作用。方法采用15只雄性大鼠建立心脏骤停及心肺复苏模型（窒息法）,自主循环恢复后,留取回肠标本,观察6、24和48小时肠粘膜的形态学改变及损伤情况：Westernblot检测回肠粘膜TLR4表达,以及ELISA法测定粘膜肿瘤坏死因子-α（TNF-α）的释放。结果复苏后动物肠粘膜显著受损,损伤程度均明显高于假手术组（sham）（P〈0．01）,其中6小时组为甚;TLR4表达在3个时间段均明显强于sham（P〈0．001）,并伴随着TNF-α表达升高。TLR4表达强弱与TNF-α释放及粘膜损伤程度变化呈正相关（P〈0．05）。结论本研究与其他疾病研究结果基本相符合,心肺复苏后肠粘膜损伤伴随着TLR4的高炎症信号,TLR4信号失控通过诱导炎性介质产生导致复苏后肠粘膜损伤。     

菊苣酸对脓毒症相关性脑病小鼠认知功能的影响

目的 探讨菊苣酸对脓毒症相关性脑病(SAE)小鼠认知功能的影响.方法 健康雄性C57BL/6小鼠60只,6～8周龄,体重20～25 g.采用随机数字表法将小鼠分为四组:假手术组(S组)、脓毒症组(P组)、菊苣酸组(CA组)和菊苣酸+SIRT1抑制剂EX527组(CE组),每组15只.P组、CA组和CE组行盲肠结扎穿孔(...     

盲肠结扎穿孔脓毒症大鼠肠黏膜通透性改变与TNF-α表达水平的关系

目的采用盲肠结扎穿孔法建立大鼠脓毒症模型,探讨其肠黏膜通透性改变与肿瘤坏死因子-α(TNF-α)表达水平的关系。方法选取48只健康雄性SD大鼠,按照随机数字表分为假手术组(n=24,仅行单纯剖腹手术)与CLP组(n=24,采用盲肠结扎穿孔法制作)。记录两组在术后6 h、12 h、24 h、48 h四个时间点(每个时间点6只)的血清二胺氧化酶(DAO)、TNF-α表达水平并行HE染色观察回肠组织病理改变情况。结果假手术组大鼠腹腔内小肠肠管无明显充血水肿等炎性表现,CLP组术后12 h回肠黏膜即开始出现局部炎性反应,至术后48 h时有明显的肠黏膜损伤性改变。假手术组大鼠在术后6 h、12 h、24 h、48 h时血清TNF-α及DAO表达水平之间的差异均无统计学意义(均P 0.05),CLP组上述时间点的血清TNF-α及DAO表达水平均高于假手术组,差异均有统计学意义(均P 0.05)。结论大鼠在盲肠结扎穿孔致脓毒症状态下可出现血清早期促炎因子TNF-α表达水平的升高,同时伴有血清DAO的变化及回肠黏膜病理改变,TNF-α等促炎因子释放引发的炎症反应可能与肠黏膜通透性改变有关。     

吸入高浓度氢气对脓毒症小鼠急性肾损伤及线粒体动力学的影响

目的评价吸入高浓度氢气对脓毒症小鼠急性肾损伤(AKI)及线粒体动力学的影响。方法雄性C57BL/6J小鼠128只, 6～8周龄, 体质量20～25 g, 采用随机数字表法分为4组(n=32):假手术组(Sham组)、假手术+氢气组(Sham+H组)、脓毒症AKI组(S-AKI)和脓毒症AKI+氢气组(S-AKI+H组)。采用盲肠结扎穿孔法建立小鼠脓毒症模型。Sham+H组和S-AKI+H组于假手术或造模后1和6 h时分别吸入67%氢气+33%氧气1 h。取20只小鼠观察造模后7 d的生存情况。于造模后24 h时, 取血标本, 采用比色法测定血清BUN和Cr浓度;取肾组织, HE染色后进行肾小管损伤评分, 采用ELISA法测定肾组织TNF-α、IL-1β和高迁移率族蛋白B1(HMGB1)的含量, 采用分光光度法测定SOD和过氧化氢酶(CAT)的活性, 采用Western blot法测定动力相关蛋白1(Drp1)和线粒体融合蛋白2(Mfn2)的表达水平。结果与Sham组比较, S-AKI组生存率降低, 血清BUN和Cr浓度、肾小管损伤评分、肾组织TNF-α、IL-1β和HMGB1含量升高,...     

帕瑞昔布钠对脓毒症大鼠肠黏膜屏障功能的影响

目的 探讨帕瑞昔布钠对脓毒症大鼠肠屏障功能的影响。 方法 采用盲肠结扎穿孔法（cecal ligation and puncture, CLP）诱导脓毒症大鼠肠损伤模型。72只Wistar大鼠按随机数字表法分为4组（每组18只）：假手术组（Sham组）、假手术＋10 mg/kg帕瑞昔布钠组（SP组）、脓毒症组（CLP组）、脓毒症＋10 mg/kg帕瑞昔布钠组（CP组）。SP组和CP组大鼠于假手术或CLP后20 min腹腔注射帕瑞昔布钠10 mg/kg,12 h后再重复注射1次。CLP组和Sham组大鼠仅经腹腔注射等量生理盐水。于假手术或CLP后24 h,检测血浆二胺氧化酶（diamine oxidase, DAO）和D-乳酸的浓度,检测各组大鼠肠组织紧密连接蛋白（zonula occludens-1, ZO-1）和Claudin-1的蛋白表达,检测肠组织髓过氧化物酶（myeloperoxidase, MPO）的活性水平。光镜检测肠组织的病理学变化。 结果 与CLP组比较,CP组脓毒症大鼠血浆中DAO和D-乳酸水平降低（P〈0.05）,MPO活性下降（P〈0.05）,CP组肠组织ZO？蛳1和Claudin-1表达上调（P〈0.05）,CP组Chiu＇s评分降低（P〈0.05）。 结论 10 mg/kg帕瑞昔布钠治疗脓毒症大鼠能够减轻肠组织损伤和炎症反应,有效降低肠黏膜的通透性,改善肠屏障功能。     

环氧合酶-2对脓毒症大鼠肝损伤的影响

目的研究环氧合酶-2（COX-2）在脓毒症大鼠的肝组织炎症反应中的表达，探索脓毒症中保护肝细胞的新途径。方法选择质量相近的Wistar大鼠54只随机分为3组：假手术组、脓毒症组及NS398组，建立盲肠结扎穿孔（CLP）脓毒症动物模型；用RT—PCR方法检测肝组织中COX-2mRNA的表达；酶联免疫吸附法（ELISA法）检测血清IL-6、TNF-α及IL-10水平变化；同时检测肝功能（ALT、AST）和肝脏病理变化。结果①肝组织中COX-2mRNA在假手术组呈低表达；脓毒症组CLP造模后3h表达明显增强，到6h达到高峰，12及24h时仍呈高表达；NS398组各时相点COX-2mRNA表达较脓毒症组明显降低（P〈0．05），但仍高于假手术组（P〈0．05）。②肝功能改变及IL-6、TNF-α水平在脓毒症组各时相点改变较假手术组和NS398组明显增高（P〈0.05）；IL-10水平NS398组高于假手术组（P〈0.05）和脓毒症组（P〈0．05）。③脓毒症组病理损伤重，NS398组肝脏病理损伤减轻。结论COX-2在脓毒症肝损伤中可能发挥重要作用。     

脓毒症大鼠肾脏高迁移率族蛋白-1与肿瘤坏死因子表达的关系

新近的研究提示 ,高迁移率族蛋白 1(highmobilitygroup 1protein ,HMG 1)作为晚期炎症介质 ,可能参与了脓毒症及其介导急性肝、肺损害的病理生理过程[1-3 ] 。本实验采用盲肠结扎穿孔法 (CLP)造成大鼠脓毒症模型 ,对肾组织HMG 1mRNA表达的改变及其与肿瘤坏死因子 (TNF)的关系进行了初步探讨。一、材料与方法1.动物分组及模型 :雄性Wistar大鼠随机分为 3组 :(1)正常对照组 (10只 ) ;(2 )盲肠结扎穿孔组 (2 0只 ) :动物麻醉后 ,沿腹正中线切开 ,在盲肠根部结扎盲肠。用 18号针穿刺盲肠 3次 ,并留置一条宽 2mm的橡皮片贯通盲肠 ,防止针…     

促炎症和抗炎症细胞因子基因表达与脓毒症小鼠肝损伤的关系

目的 探索促炎症及抗炎症细胞因子在脓毒症小鼠肝损伤中的作用。方法 盲肠结扎穿孔（ＣＬＰ）造成小鼠脓毒症模型,假手术（sham）组接受同样手术操作且不行ＣＬＰ。用ＲＴ－ＰＣＲ的方法检测了脓毒症小鼠肝组织中多种细胞因子（促炎症细胞因子ＴＮＦα、ＩＬ－１β、ＩＬ－６,抗炎症细胞因子ＩＬ－４）mＲＮＡ的表达,同时还测定了肝组织含水量及微血管通透性的改变。结果 与sham组相比,ＣＬＰ小鼠在３h后ＴＮＦα、ＩＬ－１β基因表达即明显增高（Ｐ＜０.０１）,至１２h仍然高于sham组（Ｐ＜０.０１）,但较３h有所降低;ＩＬ－６基因在ＣＬＰ后３h也明显增高（Ｐ＜０.０１）,并且在ＣＬＰ后１２h仍继续增高（Ｐ＜０.０１）;与之不同的是ＩＬ－４基因,在ＣＬＰ后３h ＩＬ－４基因表达与sham组差异无显著意义,至ＣＬＰ后１２h才明显高于sham组（Ｐ＜０.０１）。ＣＬＰ后３h肝组织含水量与肝微血管通透性即开始有所升高但与sham组比较差异无显著意义,至ＣＬＰ后１２h进一步增高与sham组比较差异均有显著意义（含水量Ｐ＜０.０５,微血管通透性Ｐ＜０.０１）。结论 促炎症细胞因子与抗炎症细胞因子之间力量对比的失衡可能是脓毒症并发肝损伤的重要原因。     

Cecal ligation and puncture as a model of sepsis in the rat: influence of the puncture size on mortality, bacteremia, endotoxemia and tumor necrosis factor alpha levels

BACKGROUND: Cecal ligation and puncture is a widely used experimental model of sepsis. AIM OF THE STUDY: The present study was aimed to evaluate the influence of the size of the cecal puncture on mortality, bacteremia, endotoxemia and plasma TNF-alpha levels. MATERIALS AND METHODS: Female Sprague-Dawley rats underwent cecal ligation and puncture, divided into the following groups, defined by the diameter of the cecal puncture: 0.5-cm blade incision (n = 25), 13-gauge (n = 25), 16-gauge (n = 25), 18-gauge puncture (n = 25) and 4 punctures with a 22-gauge needle (n = 25). A sham operation was performed in another 25 rats. Three animals of each group were sacrificed 5 h after the procedure for blood cultures as well as determination of plasma endotoxin and TNF-alpha. The remaining animals were followed up for a week after cecal ligation and puncture for evaluation of mortality. RESULTS: Five hours after cecal ligation and puncture, bacteremia was present in all animals, independently of the puncture size. Endotoxemia and plasma TNF levels tended to increase along with the diameter of the cecal puncture. Mortality gradually increased with the puncture size, from 27% with a 22-gauge needle to 95% with the blade incision. CONCLUSIONS: The severity of sepsis obtained with cecal ligation and puncture in rats can be easily modulated varying the size of the puncture.     

Evidence that tumor necrosis factor participates in the regulation of muscle proteolysis during sepsis.

The role of tumor necrosis factor (TNF) in the regulation of muscle protein turnover was studied in rats. Protein synthesis and total and myofibrillar protein breakdown rates were measured in incubated extensor digitorum longus muscles. Intraperitoneal administration of recombinant TNF-alpha (300 micrograms/kg of body weight) increased total and myofibrillar protein breakdown rates by 28% and threefold, respectively, with no effect on protein synthesis. In subsequent experiments, sepsis was induced by cecal ligation and puncture or a sham-operation was performed. Rats received TNF antiserum (1 mL/100 g of body weight) or control serum 2 hours before cecal ligation and puncture or sham-operation. Treatment with TNF antiserum reduced the mortality rate from 25% to 5% following cecal ligation and puncture. The treatment had no effect on protein synthesis but reduced total and myofibrillar protein breakdown rates by 26% and 39%, respectively, in septic animals. Results suggest TNF is involved in the regulation of sepsis-induced muscle proteolysis.     

Molecular diagnostics in sepsis: from bedside to bench

BACKGROUND: Based on recent in vitro data, we tested the hypothesis that microarray expression profiles can be used to diagnose sepsis, distinguishing in vivo between sterile and infectious causes of systemic inflammation. STUDY DESIGN: Exploratory studies were conducted using spleens from septic patients and from mice with abdominal sepsis. Seven patients with sepsis after injury were identified retrospectively and compared with six injured patients. C57BL/6 male mice were subjected to cecal ligation and puncture, or to IP lipopolysaccharide. Control mice had sham laparotomy or injection of IP saline, respectively. A sepsis classification model was created and tested on blood samples from septic mice. RESULTS: Accuracy of sepsis prediction was obtained using cross-validation of gene expression data from 12 human spleen samples and from 16 mouse spleen samples. For blood studies, classifiers were constructed using data from a training data set of 26 microarrays. The error rate of the classifiers was estimated on seven de-identified microarrays, and then on a subsequent cross-validation for all 33 blood microarrays. Estimates of classification accuracy of sepsis in human spleen were 67.1%; in mouse spleen, 96%; and in mouse blood, 94.4% (all estimates were based on nested cross-validation). Lists of genes with substantial changes in expression between study and control groups were used to identify nine mouse common inflammatory response genes, six of which were mapped into a single pathway using contemporary pathway analysis tools. CONCLUSIONS: Sepsis induces changes in mouse leukocyte gene expression that can be used to diagnose sepsis apart from systemic inflammation.     

Chronic kidney disease worsens sepsis and sepsis-induced acute kidney injury by releasing High Mobility Group Box Protein-1

We have shown that folate-induced kidney dysfunction and interstitial fibrosis predisposes mice to sepsis mortality. Agents that increase survival in normal septic mice were ineffective in a two-stage kidney disease model. Here we used the 5/6 nephrectomy mouse model of progressive chronic kidney disease (CKD) to study how CKD affects acute kidney injury (AKI) induced by sepsis. We induced sepsis using cecal ligation and puncture and found that the presence of CKD intensified the severity of kidney and liver injury, cytokine release, and splenic apoptosis. Accumulation of High Mobility Group Box Protein-1 (HMGB1; a late proinflammatory cytokine released from apoptotic cells), vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-α, interleukin (IL)-6, or IL-10 was increased in CKD or sepsis alone and to a greater extent in CKD-sepsis. Only part of the increase was explained by decreased renal clearance. Surprisingly, we found splenic apoptosis in CKD, even in the absence of sepsis. Although VEGF neutralization with soluble fms-like tyrosine kinase 1 (sFLT-1) (a soluble VEGF receptor) effectively treated sepsis, it was ineffective against CKD-sepsis. A single dose of HMGB1-neutralizing antiserum administered 6?h after sepsis alone was ineffective; however, CKD-sepsis was attenuated by anti-HMGB1. Splenectomy transiently decreased circulating HMGB1 levels, reversing the effectiveness of anti-HMGB1 treatment on CKD-sepsis. Thus, progressive CKD increases the severity of sepsis, in part, by reducing the renal clearance of several cytokines. CKD-induced splenic apoptosis and HMGB1 release could be important common mediators for both CKD and sepsis.     

Impaired cell-mediated immunity in experimental abdominal sepsis and the effect of interleukin 2.

A murine model of experimental sepsis, ie, cecal ligation and puncture, was used to determine the potential effects of infection on in vitro cell-mediated immunity. Following cecal ligation and puncture, in vitro responses of mouse splenocytes to mitogens (phytohemagglutinin and concanavalin A), the effects of in vitro interleukin 2 on these responses, and the impact of in vivo interleukin 2 on survival were studied. Compared with controls (sham cecal ligation and puncture), phytohemagglutinin responses 1 day after cecal ligation and puncture were enhanced (43% +/- 17%, n = 9), phytohemagglutinin and concanavalin A responses at day 4 were suppressed (45.5% +/- 4.4% and 57.5% +/- 5.6%), and, by day 7, phytohemagglutinin and concanavalin A responses were approaching values in mice treated by sham cecal ligation and puncture. Suppressed phytohemagglutinin responses at day 4 after cecal ligation and puncture were restored to normal with in vitro interleukin 2 (61,052 +/- 3407 cpm for cecal ligation and puncture and 64,643 +/- 4727 cpm for sham cecal ligation and puncture). Mortalities following cecal ligation and puncture were identical at day 1 after cecal ligation and puncture (6/20) for both interleukin 2- and vehicle-treated groups; thereafter, interleukin 2-treated groups fared better. At day 1 after cecal ligation and puncture, the mean spleen cell phytohemagglutinin response was enhanced (43.8% +/- 17%, n = 9) compared with sham cecal ligation and puncture (= 10). By day 4, the responses to both concanavalin A and phytohemagglutinin were suppressed (45.5% +/- 4.4% and 57.5% +/- 5.6%, respectively). Responses at day 7 approached those of controls given sham cecal ligation and puncture. Sepsis causing a temporary impairment of cell-mediated immunity may be a factor in the frequent coexistence of altered cell-mediated immunity and sepsis, and interleukin 2 may have a role in limiting the adverse effects of sepsis.     

琥珀酰明胶注射液对脓毒症大鼠A2B腺苷受体介导的肺毛细血管通透性的影响

目的研究不同剂量琥珀酰明胶注射液(改良明胶,MFG)对A2B腺苷受体(A2BAR)介导的肺毛细血管通透性的影响。方法 50只雄性SD大鼠,随机分为五组,每组10只,假手术组(S组):不结扎,不穿孔,不复苏;生理盐水组(NS组,30ml/kg);输注MFG7.5ml/kg组(MFG1组);15ml/kg组(MFG2组);30ml/kg组(MFG3组)。大鼠盲肠结扎穿孔(CLP)术后4h开始液体复苏2h,6h内持续监测HR和MAP,6h后处死动物取相应组织进行检测:肺毛细血管通透性、A2BAR含量、cAMP及PKA表达水平、TNF-α、IL-6和IL-10含量。结果与S组比较,NS、MFG1、MFG2、MFG3组肺毛细血管通透性、A2BAR表达、cAMP及PKA、TNF-α、IL-6和IL-10含量均升高(P<0.05或P<0.01)。与NS组比较,MFG组肺毛细血管通透性均降低(P<0.05);A2BAR表达,cAMP及PKA含量均升高(P<0.05或P<0.01)。TNF-α,IL-6和IL-10含量差异无统计学意义。结论 MFG可通过增强内皮细胞上A2BAR的表达及其信号通路的传导来发挥其肺血毛细血管保护作用。     

一种改良小鼠脓毒症模型的建立

目的 建立一种模拟外科临床实际,早期致死率低,用于脓毒症综合治疗研究的小鼠模型.方法 小鼠随机分为3组,即对照组、盲肠结扎穿孔(CLP)组和改良组.对照组行假手术;CLP组行盲肠结扎穿孔术;改良组通过CLP后8 h行盲肠切除和腹腔生理盐水冲洗建立脓毒症模型.观察各组动物出现死亡时间及24、48、72 h累计死亡率;术后4、12、24 h分别处死动物,检测外周血白细胞计数(VC-BC),血清内毒素、肿瘤坏死因子(TNF)水平及肺、肝病理.结果 改良组动物出现死亡时间较CLP组明显延迟,术后48、72 h累计死亡率虽明显低于CLP组(P＜0.05),但仍分别高达53.3%、80%;术后各时间点WBC较CLP组与假手术组明显升高(P＜0.05);血清内毒素和TNF-α水平明显高于假手术组,但低于CLP组;光镜下见肺泡间隔增宽,间质充血、水肿、大量炎性细胞浸润,肝细胞水肿伴散在点状坏死,肝窦扩张伴间质大量炎性细胞浸润.结论 该脓毒症改良模型具有良好的外科临床相关性,早期致死率低,可重复性好.     

Effect of bacterial sepsis on gluconeogenic capacity in the rat

Since sepsis places increased demands on the host for energy and on other substrates for tissue repair and host defense, hepatic gluconeogenesis is critical for the host's adaptation to sepsis. Substrate-stimulated gluconeogenesis (i.e., gluconeogenic capacity) was assessed by the alanine load method in mannoheptulose-pretreated rats made septic by cecal ligation after laparotomy, as well as by cecal ligation and puncture after laparotomy. Fasted rats subjected to laparotomy only (sham-ligated) and fasted, nonoperated rats (controls) were investigated simultaneously. Following an overnight (-18 to 0 hr) fast, nonoperated animals converted 17.9 +/- 1.5% of [14C]alanine to [14C]glucose. Continued fasting in nonoperated animals resulted in enhanced (P less than 0.05) gluconeogenic capacity (6 hr = 27.2 +/- 3.0%; 24 hr = 26.2 +/- 1.9%; and 48 hr = 28.5 +/- 2.6%) relative to Time 0. Laparotomy alone (sham ligation) delayed the fasting-induced increase (P less than 0.05) in gluconeogenesis capacity (6 hr = 21.1 +/- 1.2%; 24 hr = 18.5 +/- 1.3%; 48 hr = 27.8 +/- 1.0%) relative to Time 0. In contrast, postoperative sepsis produced a sustained depression (P less than 0.05) of gluconeogenic capacity relative to nonoperated sham-ligated controls at 48 hr (cecal ligation, 18.4 +/- 1.4%; and cecal ligation and puncture, 18.8 +/- 1.2%). Thus, (1) fasting enhances hepatic gluconeogenic capacity; (2) surgical trauma transiently blunts the gluconeogenic response to fasting; and (3) sepsis undermines the gluconeogenic response to fasting.