急性炎症反应中真核细胞转录因子—кB的信号转导作用

真核细胞转录因子 κB(nuclearfactorκB,NFκB)是一种普遍存在于真核细胞中具有序列特异性二聚体结构的转录因子 ,是所有 Rel家族 DNA结合蛋白的总称 ,在调节免疫应答、炎症反应及细胞增殖、分化及凋亡等方面起关键作用 〔1〕。NFκB转录复合体包括一系列由 p5 0、p5 2、Rel A(p6 5 )、Rel B和 c Rel等亚基构成的同型或异型二聚体 ,这些复合体结合到 DNA的调控区域 (称为κB位点 )后 ,激活特异靶基因的表达活性〔2〕。通常情况下 ,NFκB存在于细胞浆中 ,并与其抑制蛋白 (inhibitoryκB,IκB)家族相结合 ,后者遮蔽了 NFκB的细…     

核转录因子-κB在急性肾损伤细胞凋亡中的作用

急性肾损伤是临床常见的危重症,病死率高,缺乏有效的防治措施.研究发现,细胞凋亡在急性肾损伤的发生机制中起着重要作用.核转录因子-κB (NF-κB)是具有多向转录调节作用的核蛋白因子,与细胞凋亡关系密切,参与多种凋亡相关基因的转录调控,具有抑制和促进细胞凋亡的双向作用.本文就NF-κB信号传导在急性肾损伤细胞凋亡中的作用作一综述.     

痰热清注射液对内毒素所致全身炎症反应综合征大鼠核转录因子-κB的调控作用

目的 观察痰热清注射液对内毒素致全身炎症反应综合征(SIRS)大鼠核转录因子-κB(NF-κB)的调控作用.方法 将60只雄性Wistar大鼠随机分为正常对照组、SIRS组和痰热清组,每组20只.腹腔注射内毒素复制SIRS大鼠模型.制模成功后2 h,痰热清组腹腔注射痰热清注射液4.5 ml/kg.各组于实验后6 h开胸取心脏血,用酶联免疫吸附法(ELISA)检测NF-κB活性以及肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)的表达.结果 与正常对照组[(31.06±16.34)、(76.26±16.88)、(45.37±9.64)ng/L]比较,SIRS组大鼠NF-κB活性[(87.52±36.72)ng/L]以及TNF-α[(321.52±56.74)ng/L]和IL-1β[(136.76±19.68)ng/L]表达明显升高(P均<0.01);与SIRS组比较,痰热清组大鼠NF-κB活性[(49.51±20.51)ng/L]以及TNF-α[(183.46±30.64)ng/L]和IL-1β[(90.62±16.29)ng/L]表达明显降低(P均<0.01).SIRS组大鼠NF-κB活性与TNF-α和IL-1β表达均呈明显正相关(r1＝0.67,r2=0.43,P均<0.01).结论 痰热清注射液可明显抑制SIRS大鼠的炎症反应,其作用机制可能是抑制NF-κB的活化.     

核转录因子-κB在急性胰腺炎中的意义

1　引言急性胰腺炎 (ＡＰ)是常见的急腹症之一 ,大约有2 0 %～ 30 %的患者并发成人呼吸窘迫综合征(ＡＲＤＳ)或多器官功能不全综合征 (ＭＯＤＳ)而成为重症急性胰腺炎 (ＳＡＰ)。ＳＡＰ具有较高的病死率 ,传统的胰酶异常激活和胰腺的自身消化很难解释。近来的研究表明 ,其与白细胞过度激活、多种细胞因子作用有关 ,ＡＰ时细胞因子通过炎症介质瀑布样级联反应 ,引起胰腺及胰外多器官损害[1,2 ] 。核转录因子 κＢ(ＮＦ κＢ)是 1986年由Ｓｅｎ和Ｂａｌ ｔｉｍｏｒｅ[3] 首先从Ｂ淋巴细胞核抽提物中检测到的一种能与免疫球蛋白ｋ轻链基因增强…     

地塞米松对脑损伤大鼠核转录因子-κB水平的影响

目的 探讨地塞米松对大鼠重度创伤性颅脑损伤(TBI)后脑组织中核转录因子-κB(NF-κB)的影响.方法 将Wistar大鼠随机分为TBI组和地塞米松治疗组,采用气体冲击致大鼠重度TBI模型.各组于术后0、6、24、72、120 h取5只大鼠活杀,取脑组织,苏木素-伊红(HE)染色观察脑组织病理学变化.免疫组化检测脑组织中NF-κB水平.结果 TBI后6 h大鼠脑组织中NF-κB表达即显著升高(P<0.05),于伤后24 h达峰值(P<0.01),之后有所回降.至120 h仍维持较高水平(P<0.05或P<0.01).经地塞米松治疗后6、24、72 h脑组织中NF-kB显著低于TBI组(P均<0.01).结论 大鼠TBI后早期脑组织中NF-κB即反应性升高,并维持较高水平,引起炎症级联反应,导致TBI后继发性损伤.地塞米松可抑制NF-κB,减轻紊乱的炎症细胞因子所致的继发性损伤,起到治疗与保护作用.     

核因子κB与全身炎症反应综合征

全身炎症反应综合征(SIRS)是指机体在感染因素作用下导致机体的生理损伤和病理改变,释放体液和细胞因子,引发全身过度炎症反应的一种临床过程[1].它能够引起多器官功能障碍综合征(MODS)、急性呼吸窘迫综合征(ARDS),甚至死亡.在其发生发展过程中,许多炎症细胞释放的细胞因子及炎症介质起着抗感染的作用.但过度的或失控的炎症反应又能引起中性粒细胞介导的组织损伤和器官功能紊乱.SIRS的中性粒细胞性炎症反应是由以下物质在局部生成所致:细胞因子、趋化因子、内皮细胞白细胞粘附分子和酶,如诱导性一氧化氮合成酶(iNOS)和环氧化酶2(COX2).而这些物质的生成受到转录因子复合体核因子κB(nuclear factorkappa B,NFκB)的调节.NFκB作为近年来才发现的具有基因转录调节作用的蛋白质因子,参与了许多炎性因子的调控.因此研究如何抑制NFκB的激活,减少促炎基因的表达,从而减轻组织损伤和炎症反应以改善SIRS患者的预后具有重要意义.     

核转录因子-κB在大鼠重症急性胰腺炎中的表达

重症急性胰腺炎(SAP)病死率较高,目前尚无特异性治疗措施。近年来研究认为,包括肿瘤坏死因子、白细胞介素、血小板活化因子、磷脂酶A2、花生四烯酸代谢产物、内皮素等细胞因子、趋化     

地塞米松对脑损伤大鼠核转录因子-κB水平的影响

Objective To explore the effects of dexamethasone on nuclear factor-kB (NF-κB) expression in brain tissue after traumatic brain injury (TBI). Methods Forty rats were randomly divided into two groups: dexamethasone treatment and no treatment, and severe brain injury was produced by gas percussion in both groups. At 0, 6, 24, 72 and 120 hours after injury, 5 rats of each group were executed and the histopathological changes in brain tissue in rats were observed by hematoxylin-eosin (HE) stain. The expression of NF-κB in brain tissue of rats was detected by immunohistochemical method. Results NF-κB expression was significantly up-regulated at 6 hours in brain tissue of rats after TBI (P<0.05), reaching the highest level at 24 hours (P<0. 01). It showed a tendency to lower, but was still high at 120 hours after TBI (P<0. 05 or P<0. 01). After treatment with dexamethasone, NF-κB level was lowered at 6, 24 and 72 hours (all P<0. 01). Conclusion NF-κB expression is up-regulated in brain tissue in early period after TBI, and keeps on a high level, thus inducing inflammatory response to produce secondary injury to brain tissue. Dexamethasone shows protective effects by regulating the levels of NF-κB and prevents secondary injury which is caused by the inflammatory cytokines in rat brain tissue after TBI.     

地塞米松对脑损伤大鼠核转录因子-κB水平的影响

Objective To explore the effects of dexamethasone on nuclear factor-kB (NF-κB) expression in brain tissue after traumatic brain injury (TBI). Methods Forty rats were randomly divided into two groups: dexamethasone treatment and no treatment, and severe brain injury was produced by gas percussion in both groups. At 0, 6, 24, 72 and 120 hours after injury, 5 rats of each group were executed and the histopathological changes in brain tissue in rats were observed by hematoxylin-eosin (HE) stain. The expression of NF-κB in brain tissue of rats was detected by immunohistochemical method. Results NF-κB expression was significantly up-regulated at 6 hours in brain tissue of rats after TBI (P<0.05), reaching the highest level at 24 hours (P<0. 01). It showed a tendency to lower, but was still high at 120 hours after TBI (P<0. 05 or P<0. 01). After treatment with dexamethasone, NF-κB level was lowered at 6, 24 and 72 hours (all P<0. 01). Conclusion NF-κB expression is up-regulated in brain tissue in early period after TBI, and keeps on a high level, thus inducing inflammatory response to produce secondary injury to brain tissue. Dexamethasone shows protective effects by regulating the levels of NF-κB and prevents secondary injury which is caused by the inflammatory cytokines in rat brain tissue after TBI.     

地塞米松对脑损伤大鼠核转录因子-κB水平的影响

Objective To explore the effects of dexamethasone on nuclear factor-kB (NF-κB) expression in brain tissue after traumatic brain injury (TBI). Methods Forty rats were randomly divided into two groups: dexamethasone treatment and no treatment, and severe brain injury was produced by gas percussion in both groups. At 0, 6, 24, 72 and 120 hours after injury, 5 rats of each group were executed and the histopathological changes in brain tissue in rats were observed by hematoxylin-eosin (HE) stain. The expression of NF-κB in brain tissue of rats was detected by immunohistochemical method. Results NF-κB expression was significantly up-regulated at 6 hours in brain tissue of rats after TBI (P<0.05), reaching the highest level at 24 hours (P<0. 01). It showed a tendency to lower, but was still high at 120 hours after TBI (P<0. 05 or P<0. 01). After treatment with dexamethasone, NF-κB level was lowered at 6, 24 and 72 hours (all P<0. 01). Conclusion NF-κB expression is up-regulated in brain tissue in early period after TBI, and keeps on a high level, thus inducing inflammatory response to produce secondary injury to brain tissue. Dexamethasone shows protective effects by regulating the levels of NF-κB and prevents secondary injury which is caused by the inflammatory cytokines in rat brain tissue after TBI.     

地塞米松对脑损伤大鼠核转录因子-κB水平的影响

Objective To explore the effects of dexamethasone on nuclear factor-kB (NF-κB) expression in brain tissue after traumatic brain injury (TBI). Methods Forty rats were randomly divided into two groups: dexamethasone treatment and no treatment, and severe brain injury was produced by gas percussion in both groups. At 0, 6, 24, 72 and 120 hours after injury, 5 rats of each group were executed and the histopathological changes in brain tissue in rats were observed by hematoxylin-eosin (HE) stain. The expression of NF-κB in brain tissue of rats was detected by immunohistochemical method. Results NF-κB expression was significantly up-regulated at 6 hours in brain tissue of rats after TBI (P<0.05), reaching the highest level at 24 hours (P<0. 01). It showed a tendency to lower, but was still high at 120 hours after TBI (P<0. 05 or P<0. 01). After treatment with dexamethasone, NF-κB level was lowered at 6, 24 and 72 hours (all P<0. 01). Conclusion NF-κB expression is up-regulated in brain tissue in early period after TBI, and keeps on a high level, thus inducing inflammatory response to produce secondary injury to brain tissue. Dexamethasone shows protective effects by regulating the levels of NF-κB and prevents secondary injury which is caused by the inflammatory cytokines in rat brain tissue after TBI.     

地塞米松对脑损伤大鼠核转录因子-κB水平的影响

Objective To explore the effects of dexamethasone on nuclear factor-kB (NF-κB) expression in brain tissue after traumatic brain injury (TBI). Methods Forty rats were randomly divided into two groups: dexamethasone treatment and no treatment, and severe brain injury was produced by gas percussion in both groups. At 0, 6, 24, 72 and 120 hours after injury, 5 rats of each group were executed and the histopathological changes in brain tissue in rats were observed by hematoxylin-eosin (HE) stain. The expression of NF-κB in brain tissue of rats was detected by immunohistochemical method. Results NF-κB expression was significantly up-regulated at 6 hours in brain tissue of rats after TBI (P<0.05), reaching the highest level at 24 hours (P<0. 01). It showed a tendency to lower, but was still high at 120 hours after TBI (P<0. 05 or P<0. 01). After treatment with dexamethasone, NF-κB level was lowered at 6, 24 and 72 hours (all P<0. 01). Conclusion NF-κB expression is up-regulated in brain tissue in early period after TBI, and keeps on a high level, thus inducing inflammatory response to produce secondary injury to brain tissue. Dexamethasone shows protective effects by regulating the levels of NF-κB and prevents secondary injury which is caused by the inflammatory cytokines in rat brain tissue after TBI.     

地塞米松对脑损伤大鼠核转录因子-κB水平的影响

Objective To explore the effects of dexamethasone on nuclear factor-kB (NF-κB) expression in brain tissue after traumatic brain injury (TBI). Methods Forty rats were randomly divided into two groups: dexamethasone treatment and no treatment, and severe brain injury was produced by gas percussion in both groups. At 0, 6, 24, 72 and 120 hours after injury, 5 rats of each group were executed and the histopathological changes in brain tissue in rats were observed by hematoxylin-eosin (HE) stain. The expression of NF-κB in brain tissue of rats was detected by immunohistochemical method. Results NF-κB expression was significantly up-regulated at 6 hours in brain tissue of rats after TBI (P<0.05), reaching the highest level at 24 hours (P<0. 01). It showed a tendency to lower, but was still high at 120 hours after TBI (P<0. 05 or P<0. 01). After treatment with dexamethasone, NF-κB level was lowered at 6, 24 and 72 hours (all P<0. 01). Conclusion NF-κB expression is up-regulated in brain tissue in early period after TBI, and keeps on a high level, thus inducing inflammatory response to produce secondary injury to brain tissue. Dexamethasone shows protective effects by regulating the levels of NF-κB and prevents secondary injury which is caused by the inflammatory cytokines in rat brain tissue after TBI.     

地塞米松对脑损伤大鼠核转录因子-κB水平的影响

Objective To explore the effects of dexamethasone on nuclear factor-kB (NF-κB) expression in brain tissue after traumatic brain injury (TBI). Methods Forty rats were randomly divided into two groups: dexamethasone treatment and no treatment, and severe brain injury was produced by gas percussion in both groups. At 0, 6, 24, 72 and 120 hours after injury, 5 rats of each group were executed and the histopathological changes in brain tissue in rats were observed by hematoxylin-eosin (HE) stain. The expression of NF-κB in brain tissue of rats was detected by immunohistochemical method. Results NF-κB expression was significantly up-regulated at 6 hours in brain tissue of rats after TBI (P<0.05), reaching the highest level at 24 hours (P<0. 01). It showed a tendency to lower, but was still high at 120 hours after TBI (P<0. 05 or P<0. 01). After treatment with dexamethasone, NF-κB level was lowered at 6, 24 and 72 hours (all P<0. 01). Conclusion NF-κB expression is up-regulated in brain tissue in early period after TBI, and keeps on a high level, thus inducing inflammatory response to produce secondary injury to brain tissue. Dexamethasone shows protective effects by regulating the levels of NF-κB and prevents secondary injury which is caused by the inflammatory cytokines in rat brain tissue after TBI.     

地塞米松对脑损伤大鼠核转录因子-κB水平的影响

Objective To explore the effects of dexamethasone on nuclear factor-kB (NF-κB) expression in brain tissue after traumatic brain injury (TBI). Methods Forty rats were randomly divided into two groups: dexamethasone treatment and no treatment, and severe brain injury was produced by gas percussion in both groups. At 0, 6, 24, 72 and 120 hours after injury, 5 rats of each group were executed and the histopathological changes in brain tissue in rats were observed by hematoxylin-eosin (HE) stain. The expression of NF-κB in brain tissue of rats was detected by immunohistochemical method. Results NF-κB expression was significantly up-regulated at 6 hours in brain tissue of rats after TBI (P<0.05), reaching the highest level at 24 hours (P<0. 01). It showed a tendency to lower, but was still high at 120 hours after TBI (P<0. 05 or P<0. 01). After treatment with dexamethasone, NF-κB level was lowered at 6, 24 and 72 hours (all P<0. 01). Conclusion NF-κB expression is up-regulated in brain tissue in early period after TBI, and keeps on a high level, thus inducing inflammatory response to produce secondary injury to brain tissue. Dexamethasone shows protective effects by regulating the levels of NF-κB and prevents secondary injury which is caused by the inflammatory cytokines in rat brain tissue after TBI.     

核转录因子-κB在慢性间歇低氧大鼠各脏器的表达及其介导的炎症因子变化

目的：观察核转录因子-κB(NF-κB)在正常大鼠及慢性间歇低氧大鼠各脏器的表达差异及其信号通路介导的慢性间歇低氧大鼠机体多种炎症因子变化。方法：将30只雄性大鼠,随机分为对照组及间歇低氧组各15只。对照组常规饲料喂养,关灯睡眠;间歇低氧组每日间歇缺氧7 h。8周后处死2组大鼠,使用酶联免疫吸附法(ELISA)检测血清单核细胞趋化蛋白-1(MCP-1)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、IL-8、C-反应蛋白(CRP)。使用蛋白质印迹法(Western Blotting)分别检测2组大鼠NF-κB的蛋白表达。结果：间歇低氧组NF-κB表达较对照组增加,差异有统计学意义(P<0.01),MCP-1、TNF-α、IL-6、IL-8、CRP水平均较对照组明显增高,差异有统计学意义(P<0.01)。结论：炎症因子在慢性间歇低氧大鼠机体高表达,源于慢性间歇低氧引起的机体免疫紊乱,NF-κB介导的信号通路激活,介导了炎症反应。     

地塞米松对脑损伤大鼠核转录因子-κB水平的影响

Objective To explore the effects of dexamethasone on nuclear factor-kB (NF-κB) expression in brain tissue after traumatic brain injury (TBI). Methods Forty rats were randomly divided into two groups: dexamethasone treatment and no treatment, and severe brain injury was produced by gas percussion in both groups. At 0, 6, 24, 72 and 120 hours after injury, 5 rats of each group were executed and the histopathological changes in brain tissue in rats were observed by hematoxylin-eosin (HE) stain. The expression of NF-κB in brain tissue of rats was detected by immunohistochemical method. Results NF-κB expression was significantly up-regulated at 6 hours in brain tissue of rats after TBI (P<0.05), reaching the highest level at 24 hours (P<0. 01). It showed a tendency to lower, but was still high at 120 hours after TBI (P<0. 05 or P<0. 01). After treatment with dexamethasone, NF-κB level was lowered at 6, 24 and 72 hours (all P<0. 01). Conclusion NF-κB expression is up-regulated in brain tissue in early period after TBI, and keeps on a high level, thus inducing inflammatory response to produce secondary injury to brain tissue. Dexamethasone shows protective effects by regulating the levels of NF-κB and prevents secondary injury which is caused by the inflammatory cytokines in rat brain tissue after TBI.     

地塞米松对脑损伤大鼠核转录因子-κB水平的影响

Objective To explore the effects of dexamethasone on nuclear factor-kB (NF-κB) expression in brain tissue after traumatic brain injury (TBI). Methods Forty rats were randomly divided into two groups: dexamethasone treatment and no treatment, and severe brain injury was produced by gas percussion in both groups. At 0, 6, 24, 72 and 120 hours after injury, 5 rats of each group were executed and the histopathological changes in brain tissue in rats were observed by hematoxylin-eosin (HE) stain. The expression of NF-κB in brain tissue of rats was detected by immunohistochemical method. Results NF-κB expression was significantly up-regulated at 6 hours in brain tissue of rats after TBI (P<0.05), reaching the highest level at 24 hours (P<0. 01). It showed a tendency to lower, but was still high at 120 hours after TBI (P<0. 05 or P<0. 01). After treatment with dexamethasone, NF-κB level was lowered at 6, 24 and 72 hours (all P<0. 01). Conclusion NF-κB expression is up-regulated in brain tissue in early period after TBI, and keeps on a high level, thus inducing inflammatory response to produce secondary injury to brain tissue. Dexamethasone shows protective effects by regulating the levels of NF-κB and prevents secondary injury which is caused by the inflammatory cytokines in rat brain tissue after TBI.     

核转录因子κB在炎性相关癌症中的作用

核转录因子κB（nuclear factor—kappa B,NF—κB）是一种重要的转录因子蛋白,广泛存在于机体各种组织细胞中,对细胞因子、化学因子、生长因子、细胞黏附分子、抗凋亡蛋白基因等多种因子的表达上调起关键作用,并且在多种疾病尤其是癌症的发病机制中发挥重要的作用。     

核转录因子-κB在急性心肌梗死血管内皮细胞损伤中的作用

目的 观察急性心肌梗死(AMI)再灌注后核转录因子-κB(NF-κB)活性和血清肿瘤坏死因-α(TNF-α)、可溶性血栓调节蛋白(STM)水平的动态变化,探讨心肌缺血/再灌注对内皮细胞损伤的作用及机制.方法 随机选取进行静脉溶栓再通的AMI患者(AMI再灌注组,8例),并以健康体检者8例作为正常对照组.以电泳迁移率变动分析法(EMSA)检测NF-κB活性,放射免疫法测定TNF-α含量,酶联免疫吸附试验测量sTM水平.结果 NF-κB活性以及TNF-α和sTM水平在溶栓后0.5 h就明显升高,1 h达高峰,3、12和24 h逐渐下降;各时间点的数值均显著高于对照组(P均＜0.05);1 h时的各数值均显著高于24 h(P均＜0.05).sTM与NF-κB活性和TNF-α之间的动态变化有明显相关性(P均＜0.05).结论 AMI再灌注后存在着NF-κB活化、TNF-α增加和内皮细胞损伤;NF-κB活化可能是造成血管内皮细胞损伤的重要机制之一.