海水浸泡对大鼠小肠组织NF-κB,IκBα表达的影响

目的 观察海水浸泡并创伤大鼠小肠NF-κB,IκBα达的变化规律.方法 Wistar大鼠91只,随机分为3组:空白对照组7只,创伤组42只,海水浸泡并创伤组42只.创伤组采用腹部开放伤模型,海水浸泡并创伤组在腹部开放伤的基础上海水浸泡1 h.采用Western blotting方法测定3组小肠组织NF-κB,IκBα达量并进行统计分析和组间比较.结果 与创伤组相比,海水浸泡并创伤组伤后3 h小肠组织NF-κB的表达即出现明显增高,并一直持续到72 h(P<0.05),创伤组似较空白组略有降低,但差异无统计学意义(P>0.05);IκBα变化规律与NF-κB相反.结论 IκBα速而且持续地参与了海水浸泡并创伤大鼠的炎症反应过程,海水浸泡并创伤组大鼠伤情严重,损伤因素持续存在.在相当长一段时间内NF-κB负反馈机制并未得到建立.     

Effects of seawater immersion combined with open abdominal injury on the expression of NF-κB,and IκBαof small intestine in rats

Objective To observe effects of seawater immersion combined with open abdominal injury on the expression of NF-κB,and IκBαas well as the change pattern in rats. Methods Ninety-one Wistar rats were randomly divided into 3 groups: the control group (n =7), the open abdominal injury group(n =42) and open abdominal injury combined with 1-hour seawater immersion group ( n =42). The expression of NF-κB,andIκBαin small intestine tissues was measured by Western blot and statistical analyses were also made in the study. Results The expression of NF-κB,in the seawater immersion combined with open abdominal injury group increased significantly 3 hours after injury, when compared with that of the open abdominal injury group(P<0. 05), whereas the expression of NF-κB, of the pure injury group was slightly lower than that of the control group, but no statistical differences could be seen between them(P>0.05). The change pattern in the expression of IκBαwas quite the opposite to that of NF-κB. Conclusions NF-κB seemed to be rapidly and persistently involved in the whole inflammatory response to trauma induced by opened abdominal injury and seawater immersion, when a comparison was made with the pure open abdominal injury group. Injuries for the rats in the open abdominal injury combined with seawater immersion group were serious, and the feedback mechanism for NF-κB was not established for quite a long time.     

Effects of seawater immersion combined with open abdominal injury on the expression of NF-κB,and IκBαof small intestine in rats

Objective To observe effects of seawater immersion combined with open abdominal injury on the expression of NF-κB,and IκBαas well as the change pattern in rats. Methods Ninety-one Wistar rats were randomly divided into 3 groups: the control group (n =7), the open abdominal injury group(n =42) and open abdominal injury combined with 1-hour seawater immersion group ( n =42). The expression of NF-κB,andIκBαin small intestine tissues was measured by Western blot and statistical analyses were also made in the study. Results The expression of NF-κB,in the seawater immersion combined with open abdominal injury group increased significantly 3 hours after injury, when compared with that of the open abdominal injury group(P<0. 05), whereas the expression of NF-κB, of the pure injury group was slightly lower than that of the control group, but no statistical differences could be seen between them(P>0.05). The change pattern in the expression of IκBαwas quite the opposite to that of NF-κB. Conclusions NF-κB seemed to be rapidly and persistently involved in the whole inflammatory response to trauma induced by opened abdominal injury and seawater immersion, when a comparison was made with the pure open abdominal injury group. Injuries for the rats in the open abdominal injury combined with seawater immersion group were serious, and the feedback mechanism for NF-κB was not established for quite a long time.     

Effects of seawater immersion combined with open abdominal injury on the expression of NF-κB,and IκBαof small intestine in rats

Objective To observe effects of seawater immersion combined with open abdominal injury on the expression of NF-κB,and IκBαas well as the change pattern in rats. Methods Ninety-one Wistar rats were randomly divided into 3 groups: the control group (n =7), the open abdominal injury group(n =42) and open abdominal injury combined with 1-hour seawater immersion group ( n =42). The expression of NF-κB,andIκBαin small intestine tissues was measured by Western blot and statistical analyses were also made in the study. Results The expression of NF-κB,in the seawater immersion combined with open abdominal injury group increased significantly 3 hours after injury, when compared with that of the open abdominal injury group(P<0. 05), whereas the expression of NF-κB, of the pure injury group was slightly lower than that of the control group, but no statistical differences could be seen between them(P>0.05). The change pattern in the expression of IκBαwas quite the opposite to that of NF-κB. Conclusions NF-κB seemed to be rapidly and persistently involved in the whole inflammatory response to trauma induced by opened abdominal injury and seawater immersion, when a comparison was made with the pure open abdominal injury group. Injuries for the rats in the open abdominal injury combined with seawater immersion group were serious, and the feedback mechanism for NF-κB was not established for quite a long time.     

Effects of seawater immersion combined with open abdominal injury on the expression of NF-κB,and IκBαof small intestine in rats

Objective To observe effects of seawater immersion combined with open abdominal injury on the expression of NF-κB,and IκBαas well as the change pattern in rats. Methods Ninety-one Wistar rats were randomly divided into 3 groups: the control group (n =7), the open abdominal injury group(n =42) and open abdominal injury combined with 1-hour seawater immersion group ( n =42). The expression of NF-κB,andIκBαin small intestine tissues was measured by Western blot and statistical analyses were also made in the study. Results The expression of NF-κB,in the seawater immersion combined with open abdominal injury group increased significantly 3 hours after injury, when compared with that of the open abdominal injury group(P<0. 05), whereas the expression of NF-κB, of the pure injury group was slightly lower than that of the control group, but no statistical differences could be seen between them(P>0.05). The change pattern in the expression of IκBαwas quite the opposite to that of NF-κB. Conclusions NF-κB seemed to be rapidly and persistently involved in the whole inflammatory response to trauma induced by opened abdominal injury and seawater immersion, when a comparison was made with the pure open abdominal injury group. Injuries for the rats in the open abdominal injury combined with seawater immersion group were serious, and the feedback mechanism for NF-κB was not established for quite a long time.     

Effects of seawater immersion combined with open abdominal injury on the expression of NF-κB,and IκBαof small intestine in rats

Objective To observe effects of seawater immersion combined with open abdominal injury on the expression of NF-κB,and IκBαas well as the change pattern in rats. Methods Ninety-one Wistar rats were randomly divided into 3 groups: the control group (n =7), the open abdominal injury group(n =42) and open abdominal injury combined with 1-hour seawater immersion group ( n =42). The expression of NF-κB,andIκBαin small intestine tissues was measured by Western blot and statistical analyses were also made in the study. Results The expression of NF-κB,in the seawater immersion combined with open abdominal injury group increased significantly 3 hours after injury, when compared with that of the open abdominal injury group(P<0. 05), whereas the expression of NF-κB, of the pure injury group was slightly lower than that of the control group, but no statistical differences could be seen between them(P>0.05). The change pattern in the expression of IκBαwas quite the opposite to that of NF-κB. Conclusions NF-κB seemed to be rapidly and persistently involved in the whole inflammatory response to trauma induced by opened abdominal injury and seawater immersion, when a comparison was made with the pure open abdominal injury group. Injuries for the rats in the open abdominal injury combined with seawater immersion group were serious, and the feedback mechanism for NF-κB was not established for quite a long time.     

Effects of seawater immersion combined with open abdominal injury on the expression of NF-κB,and IκBαof small intestine in rats

Objective To observe effects of seawater immersion combined with open abdominal injury on the expression of NF-κB,and IκBαas well as the change pattern in rats. Methods Ninety-one Wistar rats were randomly divided into 3 groups: the control group (n =7), the open abdominal injury group(n =42) and open abdominal injury combined with 1-hour seawater immersion group ( n =42). The expression of NF-κB,andIκBαin small intestine tissues was measured by Western blot and statistical analyses were also made in the study. Results The expression of NF-κB,in the seawater immersion combined with open abdominal injury group increased significantly 3 hours after injury, when compared with that of the open abdominal injury group(P<0. 05), whereas the expression of NF-κB, of the pure injury group was slightly lower than that of the control group, but no statistical differences could be seen between them(P>0.05). The change pattern in the expression of IκBαwas quite the opposite to that of NF-κB. Conclusions NF-κB seemed to be rapidly and persistently involved in the whole inflammatory response to trauma induced by opened abdominal injury and seawater immersion, when a comparison was made with the pure open abdominal injury group. Injuries for the rats in the open abdominal injury combined with seawater immersion group were serious, and the feedback mechanism for NF-κB was not established for quite a long time.     

Effects of seawater immersion combined with open abdominal injury on the expression of NF-κB,and IκBαof small intestine in rats

Objective To observe effects of seawater immersion combined with open abdominal injury on the expression of NF-κB,and IκBαas well as the change pattern in rats. Methods Ninety-one Wistar rats were randomly divided into 3 groups: the control group (n =7), the open abdominal injury group(n =42) and open abdominal injury combined with 1-hour seawater immersion group ( n =42). The expression of NF-κB,andIκBαin small intestine tissues was measured by Western blot and statistical analyses were also made in the study. Results The expression of NF-κB,in the seawater immersion combined with open abdominal injury group increased significantly 3 hours after injury, when compared with that of the open abdominal injury group(P<0. 05), whereas the expression of NF-κB, of the pure injury group was slightly lower than that of the control group, but no statistical differences could be seen between them(P>0.05). The change pattern in the expression of IκBαwas quite the opposite to that of NF-κB. Conclusions NF-κB seemed to be rapidly and persistently involved in the whole inflammatory response to trauma induced by opened abdominal injury and seawater immersion, when a comparison was made with the pure open abdominal injury group. Injuries for the rats in the open abdominal injury combined with seawater immersion group were serious, and the feedback mechanism for NF-κB was not established for quite a long time.     

Effects of seawater immersion combined with open abdominal injury on the expression of NF-κB,and IκBαof small intestine in rats

Objective To observe effects of seawater immersion combined with open abdominal injury on the expression of NF-κB,and IκBαas well as the change pattern in rats. Methods Ninety-one Wistar rats were randomly divided into 3 groups: the control group (n =7), the open abdominal injury group(n =42) and open abdominal injury combined with 1-hour seawater immersion group ( n =42). The expression of NF-κB,andIκBαin small intestine tissues was measured by Western blot and statistical analyses were also made in the study. Results The expression of NF-κB,in the seawater immersion combined with open abdominal injury group increased significantly 3 hours after injury, when compared with that of the open abdominal injury group(P<0. 05), whereas the expression of NF-κB, of the pure injury group was slightly lower than that of the control group, but no statistical differences could be seen between them(P>0.05). The change pattern in the expression of IκBαwas quite the opposite to that of NF-κB. Conclusions NF-κB seemed to be rapidly and persistently involved in the whole inflammatory response to trauma induced by opened abdominal injury and seawater immersion, when a comparison was made with the pure open abdominal injury group. Injuries for the rats in the open abdominal injury combined with seawater immersion group were serious, and the feedback mechanism for NF-κB was not established for quite a long time.     

Effects of seawater immersion combined with open abdominal injury on the expression of NF-κB,and IκBαof small intestine in rats

Objective To observe effects of seawater immersion combined with open abdominal injury on the expression of NF-κB,and IκBαas well as the change pattern in rats. Methods Ninety-one Wistar rats were randomly divided into 3 groups: the control group (n =7), the open abdominal injury group(n =42) and open abdominal injury combined with 1-hour seawater immersion group ( n =42). The expression of NF-κB,andIκBαin small intestine tissues was measured by Western blot and statistical analyses were also made in the study. Results The expression of NF-κB,in the seawater immersion combined with open abdominal injury group increased significantly 3 hours after injury, when compared with that of the open abdominal injury group(P<0. 05), whereas the expression of NF-κB, of the pure injury group was slightly lower than that of the control group, but no statistical differences could be seen between them(P>0.05). The change pattern in the expression of IκBαwas quite the opposite to that of NF-κB. Conclusions NF-κB seemed to be rapidly and persistently involved in the whole inflammatory response to trauma induced by opened abdominal injury and seawater immersion, when a comparison was made with the pure open abdominal injury group. Injuries for the rats in the open abdominal injury combined with seawater immersion group were serious, and the feedback mechanism for NF-κB was not established for quite a long time.     

Effects of seawater immersion combined with open abdominal injury on the expression of NF-κB,and IκBαof small intestine in rats

Objective To observe effects of seawater immersion combined with open abdominal injury on the expression of NF-κB,and IκBαas well as the change pattern in rats. Methods Ninety-one Wistar rats were randomly divided into 3 groups: the control group (n =7), the open abdominal injury group(n =42) and open abdominal injury combined with 1-hour seawater immersion group ( n =42). The expression of NF-κB,andIκBαin small intestine tissues was measured by Western blot and statistical analyses were also made in the study. Results The expression of NF-κB,in the seawater immersion combined with open abdominal injury group increased significantly 3 hours after injury, when compared with that of the open abdominal injury group(P<0. 05), whereas the expression of NF-κB, of the pure injury group was slightly lower than that of the control group, but no statistical differences could be seen between them(P>0.05). The change pattern in the expression of IκBαwas quite the opposite to that of NF-κB. Conclusions NF-κB seemed to be rapidly and persistently involved in the whole inflammatory response to trauma induced by opened abdominal injury and seawater immersion, when a comparison was made with the pure open abdominal injury group. Injuries for the rats in the open abdominal injury combined with seawater immersion group were serious, and the feedback mechanism for NF-κB was not established for quite a long time.     

抑制NF-κB激活的策略

NF-κB是一个广泛存在于哺乳动物细胞中的转录因子。它可以参与机体的炎症反应、免疫反应、细胞分化与凋亡及其他应激反应。NF-κB启动基因的表达涉及到IKK的激活、IκB磷酸化和泛素化、IκB裂解、NF-κB向核内的迁移、NF-κB与DNA的结合等过程。NF-κB的过度激活会引起一系列的疾病，如哮喘、类风湿性关节炎、肠炎等，利用药物或通过转基因方法来抑制以NF-κB为核心的信号转导途径可能会成为防治某些疾病的途径。     

电离辐射对小鼠腹腔巨噬细胞IL-12和NF-κB活性的影响

目的　观察电离辐射对小鼠腹腔巨噬细胞IL 12和NF κB活性的影响以及两者间相互作用的关系。方法　采用酶联免疫吸附实验 (ELISA)检测IL 12蛋白水平变化 ,通过电泳凝胶移动变化分析 (EMSA)检测NF κB结合活性的变化。结果　①ELISA检测结果显示 ,腹腔巨噬细胞分泌的IL 12在 0 0 75GyX射线全身照射后 4～ 8h升高 (P <0 0 5 ) ,2Gy照射后从 2h开始升高 ,一直持续至 4 8h仍高于假照组的水平 (P <0 0 5 ) ,而且 2Gy引起IL 12升高的幅度大于 0 0 75Gy ;②EMSA检测结果显示 ,NF κB呈现两条特异带分别代表P6 5 P5 0、P5 0 P5 0两种二聚体 ,0 0 75Gy照射后P6 5 P5 0明显增高 ,最高时超过假照组的 2 0 0 % (2～ 8h) ,而P5 0 P5 0则升高不明显 ;2Gy照射后则显示P6 5 P5 0、P5 0 P5 0均明显升高 ,二者在 2～ 8h也超过假照组的 2 0 0 %。结论　IL 12表达增强和NF κB活性升高的一致性提示NF κB可能参与辐射诱导IL 12变化的分子调控。     

HIF-1α与NF-κB在妊娠期高血压疾病患者胎盘组织中的表达及意义

目的检测胎盘组织中HIF-1α和NF-κB的表达,探讨其与妊娠期高血压疾病发生的关系。方法选择2006年12月—2007年12月在我院住院分娩的孕妇50例,分为妊娠期高血压组、轻度子痫前期组、重度子痫前期组、子痫组、正常妊娠组,采用免疫组化法检测50例胎盘标本绒毛上皮组织中HIF-1α和NF-κB的表达。结果(1)妊娠期高血压疾病组HIF-1α与NF-κB表达较正常妊娠组明显升高,且差异有统计学意义(P<0.05);(2)妊娠期高血压疾病组胎盘HIF-1α与NF-κB的表达呈正相关(P<0.01),而正常妊娠组相关性不明显(P>0.05)。结论胎盘组织中HIF-1α与NF-κB的表达升高与妊娠期高血压疾病的发生有关。     

银杏叶提取物抑制人冠状动脉内皮细胞中NF-κB表达及VAP-1、IL-6生成的研究

目的：检测银杏叶提取物（Ginkgo biloba extract,EGb）能否抑制由活化血小板刺激引起的人冠状动脉内皮细胞（human coronary artery ebditgekuak cells,HCAECs）中NF-κB的表达,并降低炎症因子血管黏附蛋白-1（vascalur adhesion protein l,VAP-1）,白细胞介素6（interlenkin-6,IL-6）的生成。方法活化血小板刺激HCAECs建立氧化应激模型,使用银杏叶提取物（4、40、400μg/ml）进行干预后,通过Western Blot检测NF-κB（p65、PP65）的表达量,酶联免疫吸附试验检测VAP-1,IL-6的生成量。结果活化血小板刺激HCAECs可引起目的分子表达量的增加,检测结果显示治疗量的EGb能显著抑制p65,PP65的表达及VAP-1、IL-6的生成,并成剂量依赖性。结论银杏叶提取物能显著抑制活化血小板刺激的人冠状动脉内皮细胞中p65,PP65的表达,并降低VAP-1及IL-6的生成。     

氯胺酮对体外循环诱导外周血单核细胞NF-κB及TNF-α表达的影响

目的：观察氯胺酮对体外循环（CPB）诱导外周血单核细胞（PBMCs）中核因子-κB（NF-κB）和肿瘤坏死因子（TNF-α）表达的影响。方法：选择先天性室间隔缺损心脏病需行体外循环心脏直视手术患儿20例，随机双盲分为对照组和氯胺酮组，每组10例。氯胺酮组在CPB开始时立即给予1mg／kg氯胺酮。采用Western blot和RT-PCR测定CPB前（T0）、CPB 30min（T1）、停CPB后1h（T2）、停CPB后4h（T3），PBMCs中NF-κB P65及TNF-α mRNA的表达。结果：两组PBMCs NF-κB P65和TNF-α mRNA表达水平在T2、T3时均有不同程度升高，但在T2、T3时氯胺酮组的表达水平显著低于对照组。结论：氯胺酮对CPB诱导的PBMCs NF-κB和TNF-α表达具有一定的抑制作用。     

葛根素对糖尿病大鼠肾脏NF-κB65、TNF-α表达的影响

目的观察葛根素对糖尿病大鼠肾脏NF-κB65、TNF-α表达的影响。方法 SD大鼠随机分为正常对照组(A组),糖尿病组(B组),葛根素低、中、高剂量组(C、D、E组),每组10只。糖尿病大鼠模型建立后,C、D、E组分别给予葛根素注射液40、80、160mg/(kg·d)腹腔注射,A组和B组腹腔注射等量生理盐水。实验第8周末检测各组空腹血糖(FBG)、24h尿微量白蛋白排泄率(UAER)、肌酐(Scr)、尿素氮(BUN);采用光镜和电镜观察肾皮质形态学改变;采用免疫组织化学法检测肾组织中NF-κB65、TNF-α蛋白的表达。结果 C、D、E组FBG、UAER、Scr、BUN均高于A组(P0.01或P0.05),但明显低于B组(P0.01或P0.05)。光镜及电镜下,C、D、E组肾脏病理改变较B组明显改善,且肾组织NF-κB65、TNF-α表达较B组减少。结论葛根素能减少尿白蛋白,改善糖代谢、肾功能和肾组织结构,对糖尿病大鼠肾脏有保护作用,其机制可能与下调肾组织NF-κB65、TNF-α表达有关。     

不同剂量辛伐他汀对急性冠状动脉综合征患者NF-κB及IL-6的作用

目的观察不同剂量辛伐他汀对急性冠状动脉综合征患者外周血NF-κB及IL-6水平的影响。方法 40例急性冠状动脉综合征患者随机分为2组：10 mg辛伐他汀组（辛伐他汀10 mg/d＋常规用药）和20 mg辛伐他汀组（辛伐他汀20 mg/d＋常规用药）。分别测定治疗前后外周血NF-κB及IL-6的浓度。同期选取40例健康人作对照。结果急性冠状动脉综合征患者外周血NF-κB及IL-6水平测定值均高于对照组（P〈0.01）;两组治疗后NF-κB及IL-6的测定值均低于治疗前水平（P〈0.05）,20 mg辛伐他汀组与10 mg辛伐他汀组相比,降低外周血NF-κB及IL-6水平效果更加明显,二者差异有统计学意义（P〈0.05）。结论辛伐他汀可明显降低急性冠状动脉综合征患者外周血NF-κB及IL-6水平,且随着剂量加大,效果更加明显。     

电离辐射诱导NF-κB-HIF-1α通路在人淋巴瘤细胞中的活化

目的 观察电离辐射对恶性淋巴瘤细胞中NF-κB-HIF-1α通路的活化状态的影响,探讨恶性淋巴瘤放射抗拒的可能机制.方法 采用Western blot免疫印迹分析方法,检测5 Gy X射线照射1、4、10和20 h后,Namalwa、Ramos和Raji 3种恶性淋巴瘤细胞系中NF-κB、HIF-1α及其相关蛋白IKK的表达水平,观察1、10和50 nmol/L NF-κB抑制剂QNZ对HIF-1α等蛋白表达的影响.结果 照射4 h后,3种淋巴瘤细胞中IKK蛋白表达增加(t=8.01、5.14和5.42,P＜0.01).10 h后,3种淋巴瘤细胞核p-P65蛋白表达增加(t=11.25、17.43和22.09,P＜0.01),至20 h时表达开始下降.10～20 h时,3种淋巴瘤细胞HIF-1α蛋白表达增加,与0 h相比,差异均有统计学意义(t=19.05、12.44和12.88,P＜0.01).与单纯照射组相比,采用NF-κB抑制剂预处理3种肿瘤细胞24 h后,HIF-1α蛋白表达下降,且随药物浓度的增加而下降(t=18.69、19.35和12.26,P＜0.01).结论 电离辐射能够活化恶性淋巴瘤细胞中的NF-κB-HIF-1α通路,可能是肿瘤放射抗拒的机制之一.

Abstract：

Objective To observe the effect of X-ray radiation on NF-κB-HIF-1α pathway activation in three malignant lymphoma and to explore the mechanism of radioresistance mediated by this pathway.Methods Expression levels of p-P65,IKK and HIF-1α in Namalwa,Ramos and Raji cells were determined by Western blot 1,4,10 and 20 h after 5 Gy X-ray irradiation.The effect of QNZ on HIF-1α expression was also observed.Results Expression level of IKK protein was up-regulated 4 h after irradiation in the 3 lymphoma cell strains( t = 8.01,5.14,5.42,P ＜ 0.01 ),followed by up-regulation of p-P65 protein expression level at 10 h and HIF-1α at 10-20 h after X-ray irradiation (t = 11.25,17.43,22.09,P ＜ 0.01 ).Pretreatment of QNZ 24 h before X-ray irradiation significantly reduced the upregulation of HIF-1α protein expression induced by simple ion radiation ( t = 18.69,19.35,12.26,P ＜0.01 ).Conclusion NF-κB - HIF-1α pathway was activated in human lymphoma cells after ion radiation and may be involved in the mechanism of radioresistance.