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1.
栀子苷对缺氧/复氧小胶质细胞TLR4通路的影响   总被引:2,自引:0,他引:2  
目的研究缺氧/复氧对原代培养的小胶质细胞TLR4受体及其通路中MyD88、NF-κBp65、p-ERK1/2、p-IκBα和p38的影响和不同浓度栀子苷的干预作用,以揭示栀子苷治疗脑缺血的分子生物学机制。方法原代培养小胶质细胞,采用缺氧/复氧的方式制备模型,用栀子苷125、250和500μmol.L-1 3个浓度梯度进行干预,用逆转录聚合酶链反应检测小胶质细胞TLR4 mRNA的表达,Western blot检测TLR4、p-IκBα、p38、p-ERK1/2蛋白,免疫荧光双染观察MyD88和NF-κB;结果缺氧/复氧激活了TLR4通路,并通过MyD88依赖途径激活了下游蛋白MyD88、NF-κBp65、p-ERK1/2、p-IκBα和p38;栀子苷250和500μmol.L-1组抑制了通路蛋白的活性;结论缺氧/复氧使TLR4通路蛋白磷酸化激活。栀子苷通过对TLR4通路蛋白的抑制发挥抗炎效应,促进脑缺血的恢复。  相似文献   

2.
目的 研究栀子苷对人肝癌株细胞(Hep G2)细胞胰岛素抵抗(IR)的影响及其可能机制。方法 以高浓度胰岛素建立Hep G2胰岛素抵抗模型。通过葡萄糖试剂盒测定法,确定建立胰岛素抵抗模型所需胰岛素的浓度及作用时间。将Hep G2细胞分为3组,对照组、模型组、栀子苷组(62.5μg·m L-1作用24 h),用RT-PCR检测细胞内胰岛素受体(InsR)、核因子κB(NF-κB)的表达。结果 100 nmol·L-1胰岛素处理24 h为建立胰岛素抵抗Hep G2细胞模型的最佳条件。药物组作用后,与模型组相比,葡萄糖消耗量明显增加,差异有统计学意义(P<0.05)。药物组InsR mRNA的表达量明显高于模型组,差异有统计学意义(P<0.05),药物组NF-κB mRNA的表达量明显低于模型组,差异有统计学意义(P<0.05)。结论 栀子苷可以改善Hep G2细胞的胰岛素抵抗,主要是通过下调NF-κB的表达、上调InsR的表达来发挥其药物作用。  相似文献   

3.
目的:研究芍药总苷调控巨噬细胞核因子-κB(NF-κB)p65蛋白核的转移作用,探讨芍药总苷对NF-κB活化的影响。方法:原代培养大鼠腹腔巨噬细胞,经脂多糖和芍药总苷作用后,用Western blot方法观察NF-κB亚基p65蛋白在胞浆和胞核的表达。结果:经脂多糖刺激后,p65蛋白在胞浆中表达显著减少,在胞核中表达显著增多;芍药总苷显著增加了脂多糖刺激后p65蛋白在胞浆中的表达,并减少了其在胞核内的表达。结论:芍药总苷可抑制NF-κB p65蛋白从胞浆向胞核的转移,提示其具有抑制NF-κB活化的作用。  相似文献   

4.
贾萍  荣晓凤  丁燕  刘岳凤  田杨  张永如 《中国药房》2007,18(36):2811-2813
目的:研究芍药总苷调控巨噬细胞核因子-κB(NF—κB)p65蛋白核的转移作用,探讨芍药总苷对NF—κB活化的影响。方法:原代培养大鼠腹腔巨噬细胞,经脂多糖和芍药总苷作用后,用Western blot方法观察NF—κB亚基p65蛋白在胞浆和胞核的表达。结果:经脂多糖刺激后,p65蛋白在胞浆中表达显著减少,在胞核中表达显著增多;芍药总苷显著增加了脂多糖刺激后p65蛋白在胞浆中的表达,并减少了其在胞核内的表达。结论:芍药总苷可抑制NF—κB p65蛋白从胞浆向胞核的转移,提示其具有抑制NF—κB活化的作用。  相似文献   

5.
中药调控NF-κB活性的研究进展   总被引:5,自引:0,他引:5  
核因子-κB (nuclear factor-κB, NF-κB) 是真核细胞内广泛存在的一种转录因子,在免疫、炎症、肿瘤等众多疾病的发生发展中起着重要作用.近年来大量研究发现很多对NF-κB相关疾病具有显著疗效的中药都表现出对NF-κB的活性抑制作用,通过在细胞及分子水平上对中药的作用机理分析表明,中药中确实存在着一些活性成分,能够在细胞或分子水平上调节NF-κB的活性,发挥治疗的作用.因此,提示中药可作为筛选NF-κB活性抑制药物的天然资源库,从中筛选NF-κB活性抑制药物是可行的.本文对具有NF-κB活性抑制作用的中药提取物、单体中药、单味中药和中药复方做了综述.  相似文献   

6.
咖啡酸苯乙酯(CAPE)是源于蜂胶的小分子化合物,具有抗炎、免疫调节、抗肿瘤和抗氧化等作用,是NF-κB信号通路的特异性抑制剂,具有良好的临床应用前景。CAPE抑制多种介质诱导的NF-κB通路活化,降低肿瘤坏死因子α和白细胞介素1β等促炎因子的浓度,其机制涉及阻滞p65核转录、抑制NF-κB与DNA结合等。本综述主要介绍近年来国内外关于CAPE基于NF-κB通路的抗炎免疫和抗肿瘤药理活性研究进展,以期对该化合物的进一步研究和应用提供参考。  相似文献   

7.
目的研究胡黄连苷Ⅱ对大鼠脑缺血/再灌注后核转录因子κB(NF-κB)和NF-κB抑制因子(I-κB)表达的影响。方法应用线栓法建立大鼠大脑中动脉闭塞再灌注模型,经尾静脉注射胡黄连苷Ⅱ(10mg·kg-1)和丹参素钠(10mg·kg-1)干预治疗,原位TUNEL检测神经细胞凋亡,免疫组化检测NF-κB和I-κB的表达,ELISA法检测脑组织匀浆NF-κB和I-κB的含量。结果假手术组大鼠皮质、纹状体和海马区脑组织NF-κB和I-κB弱表达,TUNEL阳性细胞数量较少,散在分布。阴性对照组大鼠各区脑组织TUNEL阳性细胞数量较假手术组均增多,NF-κB和I-κB表达增强,脑组织匀浆NF-κB和I-κB增高(P<0.05)。阳性对照组和胡黄连苷组各区脑组织TUNEL阳性细胞数量,NF-κB和I-κB表达(A值)及脑组织匀浆NF-κB和I-κB含量均低于阴性对照组(P<0.05),阳性对照组与胡黄连苷组比较,各指标差异均无显著性(P>0.05)。结论胡黄连苷Ⅱ可能通过下调NF-κB和I-κB的表达,抑制脑缺血/再灌注损伤的炎症反应导致的神经细胞凋亡。  相似文献   

8.
霉酚酸抑制内皮细胞核因子—κB的活性   总被引:4,自引:0,他引:4  
目的:研究霉酚酸对内皮细胞核因子-κB(NF-κB)活力及其抑制因子IκBa的影响。方法:利用凝胶迁移率实验(EMSA)检测不同浓度的霉酚酸对一般培养状态和佛波脂(PMA)激活的内皮细胞的NF-κB活力影响。并用Western blot方法检测霉酚酸对NF-κB抑制因子IκBa的作用。结果:PMA显著激活内皮细胞中的NF-κB活性。降低IκBα的蛋白水平,霉酚酸抑制PMA刺激的内皮细胞NF-κB活性升高,并抑制内皮细胞胞浆IκBα蛋白的降解,结论:霉酚酸可影响内皮细胞NF-κB的活性,这可能是MPA影响内皮细胞功能的作用机制之一。  相似文献   

9.
目的探讨二苯乙烯苷(TSG)对过氧化氢(H2O2)诱导人脐静脉内皮细胞凋亡及对核因子κB(NF-κB)、NF-κB抑制因子(IκB)基因表达的影响。方法体外培养人脐静脉内皮细胞,实验分为对照组、H2O2组、TSG组,采用Ho-echst 33258染色观察细胞凋亡形态,MTT法检测细胞增殖率,流式细胞术检测细胞凋亡率,RT-PCR检测NF-κB与IκB mR-NA表达,Western blot检测NF-κB p65、IκB蛋白表达。结果与对照组比较,H2O2组凋亡细胞数增多,细胞凋亡率增加,细胞增殖降低;NF-κB mRNA和蛋白表达增加,IκB mRNA和蛋白表达降低,差异均有显著性(P<0.01)。经TSG预处理后,细胞的增殖率较H2O2组增加,细胞凋亡率减少;NF-κBmRNA和蛋白表达减少,IκB mRNA和蛋白表达增加(P<0.01)。结论二苯乙烯苷能抑制H2O2诱导的人脐静脉内皮细胞凋亡,其作用机制可能与调节NF-κB/IκB表达有关。  相似文献   

10.
目的探讨宝华玉兰种子提取物对核转录因子-κB(NF-κB)、核转录因子-κB抑制蛋白α(IκBα)表达的抑制作用机制。方法使用宝华玉兰种子提取物处理人肝癌细胞HepG2后,用Western blotting法检测NF-κB及IκBα蛋白的表达变化情况。结果宝华玉兰种子提取物对IκBα的磷酸化及降解有抑制作用。宝华玉兰种子提取物可有效抑制NF-κB介导的基因转录。结论宝华玉兰种子提取物可能通过抑制IκBα磷酸化及降解,阻断NF-κB活性,进而抑制COX-2而发挥其抗炎和抗肿瘤作用。  相似文献   

11.
Identification of novel target pathways in glioblastoma (GBM) remains critical due to poor prognosis, inefficient therapies and recurrence associated with these tumors. In this work, we evaluated the role of nuclear-factor-kappa-B (NFκB) in the growth of GBM cells, and the potential of NFκB inhibitors as antiglioma agents. NFκB pathway was found overstimulated in GBM cell lines and in tumor specimens compared to normal astrocytes and healthy brain tissues, respectively. Treatment of a panel of established GBM cell lines (U138MG, U87, U373 and C6) with pharmacological NFκB inhibitors (BAY117082, parthenolide, MG132, curcumin and arsenic trioxide) and NFκB-p65 siRNA markedly decreased the viability of GBMs as compared to inhibitors of other signaling pathways such as MAPKs (ERK, JNK and p38), PKC, EGFR and PI3K/Akt. In addition, NFκB inhibitors presented a low toxicity to normal astrocytes, indicating selectivity to cancerous cells. In GBMs, mitochondrial dysfunction (membrane depolarization, bcl-xL downregulation and cytochrome c release) and arrest in the G2/M phase were observed at the early steps of NFκB inhibitors treatment. These events preceded sub-G1 detection, apoptotic body formation and caspase-3 activation. Also, NFκB was found overstimulated in cisplatin-resistant C6 cells, and treatment of GBMs with NFκB inhibitors overcame cisplatin resistance besides potentiating the effects of the chemotherapeutics, cisplatin and doxorubicin. These findings support NFκB as a potential target to cell death induction in GBMs, and that the NFκB inhibitors may be considered for in vivo testing on animal models and possibly on GBM therapy.  相似文献   

12.
与A20结合的核因子κB抑制蛋白1(A20 binding inhibitor of NF-κB activation,ABIN1)是近年来研究发现的一个新泛素结合蛋白。最初的研究表明,ABIN1通过结合锌指结构蛋白A20在NF-κB信号通路中发挥重要的调节作用。目前发现,ABIN1在过表达的条件下能抑制肿瘤坏死因子、白细胞介素1、脂多糖、表皮生长因子等诱导的NF-κB的活性,从而发挥抗炎和免疫调节作用。因此,以ABIN1为新靶点调节NF-κB活性的研究日益受到关注。本文就ABIN1蛋白结构、功能及其研究进展做一综述。  相似文献   

13.
BackgroundApproaches promoting fibroblast-like synoviocytes (FLS) apoptosis are considered as a meaningful strategy for rheumatoid arthritis (RA) treatment. We have previously reported the anti-arthritic effect of penta-acetyl geniposide ((Ac)5GP, an active derivative of geniposide) on adjuvant-induced arthritis (AIA) rats in vivo. The present study aimed to investigate the pro-apoptotic effect of (Ac)5GP on AIA FLS in vitro and the underlying molecular mechanisms.MethodsRat AIA was induced by complete Freund’s adjuvant, and FLS were primary-cultured from synovial tissues. AIA FLS were treated with (Ac)5GP (50, 100 and 200 μM) for 48 h and cell proliferation and apoptosis were respectively examined. The involvement of apoptosis-related proteins (Bax, Bcl-2 and caspase 3) and nuclear factor kappa B (NF-κB) signaling pathway was checked.Results(Ac)5GP inhibited the viability of AIA FLS and reduced the percentage of Ki67-positive cells in AIA FLS. Particularly, (Ac)5GP promoted AIA FLS apoptosis in vitro by inducing apoptotic nuclear morphology, facilitating DNA ladder formation and increasing percentages of both early and late apoptotic cells. (Ac)5GP treatment on AIA FLS decreased Bcl-2 protein level whereas increased the levels of Bax and caspase 3 proteins. Moreover, (Ac)5GP reduced the degradation and phosphorylation of IκBα, down-regulated NF-κB p65 protein level in nucleus and inhibited NF-κB p65 nuclear translocation.Conclusions(Ac)5GP had a potent pro-apoptotic effect on AIA FLS in vitro, which is associated with regulating apoptosis-related proteins and inhibiting NF-κB activation.  相似文献   

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Importance of the field: Nuclear factor kappa B (NF-κB) is activated by a variety of cancer-promoting agents. The reciprocal activation between NF-κB and inflammatory cytokines makes NF-κB important for inflammation-associated cancer development. Both the constitutive and anticancer therapeutic-induced NF-κB activation blunts the anticancer activities of the therapy. Elucidating the roles of NF-κB in cancer facilitates developing approaches for cancer prevention and therapy.

Areas covered in this review: By searching PubMed, we summarize the progress of studies on NF-κB in carcinogenesis and cancer cells' drug resistance in recent 10 years.

What the reader will gain: The mechanisms by which NF-κB activation pathways are activated; the roles and mechanisms of NF-κB in cell survival and proliferation, and in carcinogenesis and cancer cells' response to therapy; recent development of NF-κB-modulating means and their application in cancer prevention and therapy.

Take home message: NF-κB is involved in cancer development, modulating NF-κB activation pathways has important implications in cancer prevention and therapy. Due to the complexity of NF-κB roles in different cancers, careful evaluation of NF-κB's in each cancer type is crucial in this regard. More cancer cell-specific NF-κB inhibiting means are desired for improving anticancer efficacy and reducing systemic toxicity.  相似文献   

18.
Nuclear factor kappa B (NFκB) has emerged as a crucial regulator of cell survival, playing important functions in cellular resistance to oxidants and chemotherapeutic agents. Recent studies showed that NFκB mediates cell survival through suppression of the accumulation of reactive species (RS) and a control of sustained activation of the Jun-N-terminal kinase (JNK) cascade. This work was undertaken in order to evaluate the role of NFκB in modulating the pro-oxidant effects of supplementation with vitamin A (retinol, ROH) in Sertoli cells, a major ROH physiological target. In this work, we reported that ROH treatment increases mitochondrial RS formation leading to a redox-dependent activation of NFκB. NFκB activation played a pivotal role in counteract RS accumulation in ROH-treated cells, since NFκB inhibition with DNA decoy oligonucleotides or pharmacological inhibitors (BAY-117082) potentiated ROH-induced RS accumulation and oxidative damage. In the presence of NFκB inhibition, ROH-induced oxidative stress promoted a prolonged activation of the JNK-activator protein 1 (AP-1) pathway and induced significant decreases in cell viability. Inhibition of JNK-AP-1 with decoy oligonucleotides to AP-1 or JNK inhibitor SP600125 prevented the decreases in cell viability. Antioxidants blocked the persistent JNK-AP-1 activation, cell oxidative damage, and the decreases in cell viability induced by NFκB inhibition. Finally, our data point superoxide dismutase (SOD)2 as a potential antioxidant factor involved in NFκB protective effects against ROH-induced oxidative stress. Taken together, data presented here show that NFκB mediates cellular resistance to the pro-oxidant effects of vitamin A by inhibiting RS accumulation and the persistent and redox-dependent activation of JNK-AP-1 cascade.  相似文献   

19.
NF-κB transmits signals from the cell surface to the nucleus. Signaling through cell surface receptors to activate NF-κB and mitogen-activated protein kinases through adaptor molecules is of critical importance to survival and activation of all cells in the body, including those regulating innate and adaptive immunity. As such, NF-κB is a key signaling component in autoimmunity and an attractive target for autoimmune disease therapy. However, given its global importance, targeting NF-κB tends to be immunosuppressive. In this review, the authors discuss the roles played by NF-κB in autoimmunity, drugs which target it, and complexities which need to be addressed to improve the use of NF-κB as a target. Finally, the authors highlight some novel approaches that are likely to be important in the next generation of NF-κB therapies.  相似文献   

20.
目的:探讨胆囊收缩素-8(cholecystokinin-8,CCK-8)对高血压性大鼠脑出血后血肿周围组织核因子-κB ( Necular Factor Kappa B ,NF-κB)活性的影响。方法取成年SD大鼠72只,体重250~300 g,随机分假手术组( n =12)、脑出血组( n =24)和CCK-8治疗组( n =24)。采用电泳迁移率改变分析方法(electrophoretic mobility shift assay , EMSA)检测核内NF-κB的活性,用免疫组化方法观察NF-κB在细胞内的表达情况,并用干湿重法测量出血侧脑组织含水量。结果脑出血组各时间点NF-κB的活性以及脑含水量较假手术组和CCK-8治疗均有明显增高( P <0妹.05)。结论脑出血后,脑组织NF-κB的表达明显增加,CCK-8可以有效的抑制NF-κB的活性,这对于减轻NF-κB在脑出血后介导的继发性炎性损害起到了积极的作用。  相似文献   

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