核因子E2相关因子2转录调控粒状头样2基因影响上皮性卵巢癌细胞活力

目的 探讨核因子E2相关因子2（Nrf2）及其下游基因粒状头样2（GRHL2）对上皮性卵巢癌是否影响以及增殖细胞在上皮性卵巢癌细胞中Nrf2对GRHL2基因的调控作用。 方法 采用染色质免疫共沉淀方法检测Nrf2是否与6种候选基因结合。采用Nrf2过表达结合荧光素酶报告基因实验，检测Nrf2对GRHL2基因的转录激活作用。采用Real-time PCR实验，分析卵巢癌患者输卵管上皮组织及不同卵巢癌细胞中Nrf2和GRHL2在mRNA水平的表达。采用Western blotting技术，分析Nrf2过表达和敲降对GRHL2蛋白表达量的影响。采用细胞计数试剂盒-8（CCK-8）实验检测Nrf2过表达和敲降对卵巢癌细胞活力的影响。 结果 Nrf2可以与GRHL2启动子结合，对GRHL2基因有转录激活的作用。Nrf2过表达和敲降分别升高和降低GRHL2蛋白质表达量；并且，在卵巢癌患者输卵管上皮组织及不同类型卵巢癌细胞系中Nrf2和GRHL2 mRNA水平均异常升高；Nrf2过表达和敲降分别升高和降低卵巢癌细胞活力，而GRHL2敲降可显著降低Nrf2过表达对卵巢癌细胞活力的增强作用。 结论 转录因子Nrf2可通过转录激活GRHL2基因，发挥对卵巢癌细胞活力的增强作用。     

核因子E2相关因子2在神经细胞衰老及其相关疾病中的作用

衰老是正常身体功能逐渐出现生物学损伤的过程,中枢神经系统最容易受到影响。目前关于衰老的机制探讨有很多,其中氧化应激被广泛关注。核因子E2相关因子2(Nrf2)作为一种维持人体内氧化还原平衡和信号转导的重要转录因子,可以激活抗氧化反应元件(ARE)以保护大脑免受氧化应激的损伤,从而在抗衰老及相关疾病中起到积极作用。Nrf2的缺失与神经元变性、星型胶质细胞以及小胶质细胞的过度活化有关,其后果是引起衰老及相关疾病。本文对Nrf2与各类神经细胞衰老的关系以及Nrf2在衰老相关神经系统疾病中的作用进行了综述。     

姜黄素对大鼠睾丸缺血再灌注损伤后的保护作用及核因子E2相关因子2表达的影响

目的 ：探究姜黄素对大鼠睾丸缺血再灌注损伤后的保护作用及核因子E2相关因子2(Nrf2)表达的影响。方法 ：32只4周龄健康雄性SD大鼠随机分为假手术组、生理盐水组、姜黄素单次给药组（术中灌注姜黄素）、姜黄素连续给药组（术中及术后7 d灌注姜黄素）,每组8只。建立左侧睾丸扭转复位动物模型,于缺血再灌注损伤后1周用彩色多普勒超声观察睾丸损伤情况;术后6周处死大鼠,取左侧睾丸,测量精子活动率及精子计数;睾丸组织切片H-E染色观察睾丸组织病理改变;qRT-PCR检测各组大鼠睾丸Nrf2表达的差异。结果 ：姜黄素给药组能明显提高大鼠睾丸缺血再灌注损伤后精子活动率、精子计数水平,且能显著改善睾丸组织损害程度。姜黄素给药组睾丸Nrf2的表达水平明显高于缺血再灌注损伤组。结论 ：姜黄素能够上调缺血再灌注损伤后睾丸Nrf2的表达,有效减轻睾丸缺血再灌注损伤,从而对青春前期大鼠单侧睾丸扭转起到明显的远期保护作用,且连续给药优于单次给药。     

核因子E2相关因子2对人永生化角质形成细胞氧化损伤的保护作用

目的 探讨核因子E2相关因子2(Nrf2)对过氧化氢(H2O2)诱导的人永生化角质形成细胞(HaCaT)氧化损伤的保护作用.方法 用慢病毒转染方式使HaCaT过表达Nrf2(Nrf2/HaCaT),并用MTT法和抗Ki67免疫荧光染色法检测其增殖活性.实验分为Nrf2/HaCaT组和HaCaT组,每组5个样本.应用20...     

抗氧化应激转录因子-Nrf2的研究进展

细胞毒物、致癌物以及亲电子试剂在外界环境中无处不在,这些物质及其代谢产物直接或间接干扰DNA、蛋白质和脂质等生物大分子的生理功能,参与各种疾病包括肿瘤、老化、哮喘、急性肺损伤、动脉粥样硬化、神经退行性疾病和自身免疫病等疾病的病理生理过程,时刻威胁人类健康。为了对抗各种外来物质的攻击,细胞在进化过程中逐渐获得了对抗这些毒性物质的防御能力。其中一个对抗氧化应激最重要的细胞防御机制是由核因子E2相关因子2(nuclear factor-E2-related factor 2,Nrf2)所介导的,Nrf2通过与胞浆蛋白Kelch样环氧氯丙烷相关蛋白-1(Kelch-like epichlorohydrin-associated protein 1,Keap1)以及抗氧化反应元件(antioxidant response element,ARE)相互作用,启动下游编码抗氧化蛋白和II相解毒酶的基因表达,发挥细胞保护作用。     

核因子E2相关因子2与肾间质纤维化研究进展

肾间质纤维化（renal interstitial fibrosis,RIF）是慢性肾衰竭的主要原因之一,是各种慢性肾脏疾病的共同结果,其发病机制与肾间质成纤维细胞,肾小管上细胞,炎性细胞以及肾小管周围毛细血管内皮细胞的转型,损伤和数量相关。氧化应激是导致细胞损伤、衰老和死亡的主要原因之一,其在神经退行性疾病、缺血性心脏病、肝、肺纤维化和癫痫等重要疾病的发生和发展中起重要作用。     

Nrf-2基因过表达对急性胰腺炎大鼠胰腺的保护作用

目的探讨Nrf-2基因过表达对急性胰腺炎大鼠胰腺的保护作用。方法 32只雄性SD大鼠随机分为4组:正常对照组(NC)、Nrf-2过表达组(Nrf-2^+/+)、胰腺炎组(AP)、Nrf-2过表达胰腺炎组(Nrf-2^+/++AP)。各组均采用尾静脉注射慢病毒感染后,AP组和Nrf-2^+/++AP组通过腹腔内注射蛙皮素和脂多糖造模;造模后24 h处死大鼠取材,ELISA法检测大鼠血清C-反应蛋白(CRP)含量;检测胰腺组织超氧化物歧化酶(SOD)、丙二醛(MAD)和髓过氧化物酶(MPO)水平;RT-PCR检测胰腺Nrf-2mRNA相对表达量;Western blot检测Nrf-2蛋白相对表达量;H&E染色观察大鼠胰腺组织细胞形态。结果 AP组与NC组相比,大鼠血清C反应蛋白含量显著升高,SOD活性明显降低,MDA含量和MPO活性明显高于AP组,且AP组胰腺组织损伤较NC组明显增加;与AP组相比,Nrf-2过表达后,Nrf-2^+/++AP组大鼠血清C反应蛋白含量显著降低,SOD活性明显升高,MDA含...     

核转录因子—kB与前列腺肿瘤

按转录因子NF—kB具有多向性调节作用，可在多种因素作用下被激活，参与调控多种基因的表达；参与免疫反应、胚胎发育、凋亡、肿瘤形成和转移等多种生理及病理过程；并与肿瘤转移过程中起重要作用的粘附分子和细胞外基质蛋白水解酶等分泌调节有关．酣列腺肿瘤的发生、发展及浸润转移，与NF—kB及其抑制因子间正常平衡的破坏及随之而来的系列NF—kB依赖基因表达的改变密切相关．本文综述了NF—kB与恶性肿瘤发生、发展、浸润转移的关系及与NF—kB相关的抗肿瘤策略．     

大鼠肝癌发生过程中肿瘤坏死因子相关的凋亡诱导配体及核转录因子-κB的表达

目的:探讨肿瘤坏死因子相关的凋亡诱导配体(TRAIL)及核转录因子κB(NF-κB)在大鼠肝癌发生过程巾的表达及意义.方法:应用免疫组织化学SP法,对二乙基亚硝胺(DEN)诱发的大鼠肝癌发生过程中TRAIL及NF-κB的动态表达进行检测.结果:二乙基亚硝胺诱发的肝癌为肝细胞癌,大鼠肝癌癌变过程大致经过肝细胞损伤期、肝细胞增生-硬化期和肝细胞癌变期3个阶段.在正常大鼠肝、损伤期及增生硬化期偶见少量肝细胞呈TRAIL阳性表达,进入癌变期,TRAIL阳性细胞数量增多,主要位于癌结节内.在正常大鼠肝,偶见少量肝细胞呈NF-κB阳性表达,随着肝癌发生发展,阳性表达细胞逐渐增多,至诱癌晚期,可见大量NF-κB阳性表达细胞,均比正常肝组织表达高.结论:TRAIl及NF-κB可能与肝癌的发生发展密切相关.     

The characterization of squamous cell carcinoma induced by ultraviolet irradiation in hairless mice

Squamous cell carcinomas (SCCs) induced by ultraviolet irradiation in hairless mice were characterized according to their growth, gross appearance and light and transmission electron microscopic features. SCCs arose directly from irradiated skin (ab initio) or progressed from pre-existing epidermal tumours and lesions. SCCs could be graded using guidelines established for human tumours. SCCs comprised 60.8% of the tumours examined. Of these, 35.6% were designated as grade 1, 27.7% as grade 2, 7.9% as grade 3 and 28.7% as grade 4. Spindle cell tumours suspected of being SCCs were included in grade 4. Grades 1, 2 and 3 could not be distinguished on the basis of growth and gross appearance. Those arising ab initio presented as either red, ulcerated lesions or as raised, white, verrucose lesions. Grade 4 SCCs that arose ab initio presented as rapidly growing, red, spherical lesions. Those that arose from pre-existing tumours or lesions had no characteristic appearance, and variable growth. Light microscopically, grade 4 SCCs with an obvious point of origin from epidermis or other epidermal tumours, and putative grade 4 SCCs without such a point of origin, were characterized commonly by spindle cells, pleomorphic giant or multinucleated cells and individual cell reticular fibres. Ultrastructurally, spindle cells, although poorly differentiated, were distinct from flibroblastic proliferations and had few tonofilaments or desmosomes, and were inconsistently surrounded by basal lamina-like material. On the basis of these characteristics, and despite inconclusive positivity with immunoperoxidase staining for keratin and prekeratin, it was concluded that these spindle cell tumours were most probably of identical squamous cell origin.(ABSTRACT TRUNCATED AT 250 WORDS)     

Bax gene disruption alters the epidermal response to ultraviolet irradiation and in vivo induced skin carcinogenesis

Bcl-2 family member proteins are differentially expressed in skin and in non-melanoma skin cancer (NMSC). To elucidate the contribution of bcl-2 and bax proteins to epidermal differentiation and skin carcinogenesis, we investigated keratinocyte proliferation, differentiation and tumourigenesis in bcl-2(-/-) and bax(-/-) mice. The rate and pattern of proliferation and spontaneous cell death in the bcl-2(-/-) and bax(-/-) mice were not different from control mice. The epidermis of bcl-2(-/-) and bax(-/-) expressed sightly higher levels of cytokeratin 1 and loricrin compared to control littermates. The apoptotic response to ultraviolet-induced genotoxic stress was assessed by quantitating TUNEL positive cells. Bax(-/-) keratinocytes showed a significant resistance to UV-induced cell death compared to control mice. The life-span of bcl-2(-/-) mice precluded an assessment of bcl-2 gene disruption on in vivo tumourigenesis. A significant increase in tumour incidence was observed in bax(-/-) mice compared to control mice in two-step chemical carcinogenesis studies. These findings suggest that bcl-2 and bax gene products may be important determinants of normal keratinocyte differentiation and response to genotoxic stress in vivo, and indicate that bax may provide a tumour suppressor effect during skin carcinogenesis.     

Effect of experimental ultraviolet irradiation of blood on immunity

Clinic for Pediatric Surgery, Anesthesiology, and Resuscitation, Second Moscow Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR A. D. Ado.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 113, No. 2, pp. 178–179, February, 1992.