核因子κB信号通路在脓毒症中对多器官功能障碍影响的研究进展

脓毒症的定义是因机体对感染反应失调所引起的危及生命的器官功能障碍。目前普遍认为病原体的致病性在脓毒症中处于核心地位,但是仅仅靠病原体的致病性并不能完全解释宿主中过度激活的炎症反应及相应的器官功能障碍。越来越多的证据提示相关信号通路失调在脓毒症的发生发展中起着不可替代的作用,而核因子κB(NF-κB)则是调节宿主对感染反应的关键转录因子,并在脓毒症当中协调固有免疫及获得性免疫。本文查阅了近年来的国内外文献,就NF-κB信号传导途径及NF-κB传导通路与器官功能障碍之间的关系进行详细的阐述,以此为临床上脓毒症的诊断及治疗提供新的思路。

NF-κB信号传导通路相关基因不同表型肝癌患者尿8-OHdG水平观察

目的观察NF-κB信号传导通路相关基因不同表型的肝癌患者尿8-羟基脱氧鸟苷(8-OHdG)水平。方法 PCR-RFLP法检测155例肝癌患者(肝癌组)NF-κB信号传导通路中TNF-α、NF-κB、iNOS、COX-2的基因表型。采用ELISA法检测肝癌组及151例健康体检者(对照组)的尿8-OHdG。结果肝癌组尿8-OHdG水平为(9.29±8.04)ng/mg Cr,对照组为(7.27±5.06)ng/mg Cr,两组相比,P<0.05。肝癌组NF-κB信号传导通路相关基因TNF-α、NF-κB、iNOS、COX-2基因不同表型组尿8-OHdG水平相比,P均>0.05。结论肝癌患者尿8-OHdG水平高于正常,可能与肝癌发病有关。NF-κB信号传导通路相关基因多态性与肝癌患者尿8-OHdG水平无明显关系。

中药调控核因子-κB(NF-κB)信号通路治疗银屑病的研究进展

银屑病是一种慢性自身免疫性皮肤病,其核心是免疫反应失调和角质形成细胞增殖异常。核因子-κB(NF-κB)在银屑病中是一种关键的调节信号通路,通过抑制NF-κB信号途径或下游转录因子肿瘤坏死因子-α(TNF-α)或白细胞介素-17(IL-17)/白细胞介素-23(IL-23)成为未来银屑病治疗的一个新方向。中药针对NF-κB信号通路在银屑病治疗中具有疗效确切、手段多样、不良反应小等优势。总结了中药调控丝裂原活化蛋白激酶(MAPK)/NF-κB、NF-κB/信号传导和转录激活因子3(STAT3)、Toll样受体4(TLR4)/NF-κB信号通路治疗银屑病的研究进展,以期为中药治疗银屑病提供更新策略。

An Experimental Study on the Role of Nuclear Factor-κB in the Signal Conduction of Protein Kinase C Regulating the Proliferation and Apoptosis of T Lymphocytes in Asthma

To explore the role of nuclear factor-κB(NF-κB) in the signal pathway of protein kinase C (PKC) regulating the proliferation and apoptosis of T lymphocytes in asthma. T lymphocytes were isolated from the asthmatic model of guinea pigs and the asthmatic patients. Either the T cells stimulated with PMA alone or those stimulated with PMA together with pyrrolidine dithiocarbamate (PDTC) were incubated for 1 and 24?h. The proliferation of and the presence of NF-κB in the cells incubated for 1?h were observed by MTT and immunohistochemical staining, respectively. And the cells incubated for 24?h were observed for the apoptosis by TUNEL. All the assays were paralleled with controls, and all the data were analyzedstatistically with the software SAS. The percentage of cells of nuclear positive staining of NF-κB and the proliferation of T lymphocytes from asthmatic guinea pigs and asthmatic patients stimulated with PMA were significantly higher than those of T lymphocytes from asthmatic guinea pigs and asthmatic patients stimulated without PMA respectively (P<0.01) and those of T lymphocytes from normal control guinea pigs and normal control persons stimulated with PMA respectively (P<0.01), and were significantly reduced by PDTC (P<0.01). The apoptosis index of T lymphocytes from asthmatic guinea pigs and asthmatic patients stimulated with PMA were significantly lower than those of T lymphocytes from asthmatic guinea pigs and asthmatic patients stimulated without PMA respectively (P<0.01) and those of T lymphocytes from normal control guinea pigs and normal control persons stimulated with PMA respectively (P<0.01), and were significantly induced by PDTC (P<0.01). There were good positive correlation between the percentage of cells of nuclear staining of NF-κB of T lymphocytes and the proliferation of T lymphocytes (r=0.51-0.72, P<0.001), and also good negative correlation between the percentage of cells of nuclear staining of NF-κB and the apoptosis index of T lymphocytes (r=-0.55-0.71, P<0.001, respectively). It concludes that the active PKC of asthmatic T lymphocytes promoting the proliferation and inhibiting the apoptosis of T lymphocytes may be mediated by activating NF-κB, the activation of PKC-NF-κB signal pathway of T lymphocytes NF-κB may play an important role in the pathogenesis of asthma.

基于NF-κB/STAT信号通路探究朱砂根治疗大鼠急性咽炎的作用机制

目的建立大鼠急性咽炎模型并结合网络药理学,基于核因子-κB(nuclear factor-κB,NF-κB)/信号传导及转录激活因子(signal transducer and activator of transcription,STAT)信号通路探讨朱砂根Ardisia crenata干预大鼠急性咽炎的作用机制。方法通过网络药理学方法预测朱砂根干预急性咽炎的靶点,构建活性成分-靶点、靶点-通路网络。构建急性咽炎大鼠模型,检测大鼠血清中白细胞介素-6(interleukin-6,IL-6)、前列腺素E2(prostaglandin E2,PEG2)和IL-10水平;采用qRT-PCR检测大鼠咽部组织中半胱氨酸天冬氨酸蛋白酶-3(cystein-asparate protease-3,Caspase-3)、Caspase-7、Caspase-8、蛋白酪氨酸性磷酸非受体型11(protein tyrosine phosphatase nonreceptor 11,PTPN11)、蛋白激酶B1(protein kinase B1,AKT1)和Janus激酶2(Janus kinase 2,JAK2)mRNA表达;采用Western blotting检测大鼠咽部组织中AKT1、JAK2和Caspase-8蛋白表达。结果网络药理学研究显示,朱砂根主要活性成分与急性咽炎有168个交集靶点,主要作用于NF-κB/STAT信号通路。与模型组比较,朱砂根组大鼠血清中IL-6和PEG_(2)水平明显降低(P<0.01),IL-10水平显著升高(P<0.05、0.01);咽部组织Caspase-3、Caspase-7、Caspase-8、PTPN11、AKT1和JAK2 mRNA表达水平均显著降低(P<0.05、0.01),Caspase-8、AKT1和JAK2蛋白表达水平均显著降低(P<0.05、0.01)。结论朱砂根中的活性成分可能通过调控NF-κB/STAT信号通路,干预炎症反应并加速巨噬细胞分化、凋亡,从而治疗急性咽炎。