核因子-κB在高脂饮食诱导的大鼠胰腺损伤中的作用

目的研究长期高脂饮食诱导的大鼠胰腺损伤及核因子-κB(NF-κB)在其发病机制中的作用。方法雄性Wistar大鼠14只分为高脂组和正常对照组,分别给予正常饮食和高脂饮食喂养20周。检测血清三酰甘油、总胆固醇及淀粉酶、脂肪酶、葡萄糖水平;常规HE染色观察胰腺病理改变;透射电镜观察胰腺超微结构改变;苦味酸-天狼猩红染色观察胶原形成;免疫组织化学染色检测NF-κB/p65、细胞间黏附分子-1(ICAM-1)和α-平滑肌动蛋白(α-SMA)表达;RT-PCR法检测胰腺组织中NF-κB/p65、ICAM-1、TNF-α、α-SMAmRNA水平。结果高脂组大鼠喂养2周后即出现高脂血症,20周末,高脂组大鼠血清三酰甘油和总胆固醇均高于对照组(P<0.01)。20周后高脂组大鼠胰腺组织腺泡细胞萎缩、空泡变性;内质网明显扩张,血管内皮细胞间隙增宽,血管内皮断续;胰腺组织内有胶原形成。高脂组大鼠胰腺NF-κB/p65、ICAM-1和α-SMA蛋白高表达;高脂组大鼠NF-κB/p65、ICAM-1、TNF-α、α-SMAmRNA水平均较对照组明显增高(P<0.05或P<0.01)。结论长期高脂饮食可引起高脂血症和胰腺组织损伤,其分子机制与NF-κB活化及其下游分子的表达增强有关。     

罗格列酮对高脂饮食大鼠胰腺核因子-κB表达和β细胞凋亡的影响

目的 观察高脂饮食对大鼠胰腺核因子(NF)-κB表达及胰岛β细胞凋亡的影响及罗格列酮干预作用.方法 雄性Wistar大鼠40只随机分为正常对照(NC)组(16只)和高脂对照(HF)组(24只),喂养第4周HF组中随机分出8只大鼠给予罗格列酮(RSG)灌胃,即RSG组.喂养第4、8周每组分别取8只行高胰岛素-正葡萄糖钳夹试验测葡萄糖输注率(GIR),随后处死大鼠并测胰岛素、生化等指标,TUNEL法观察β细胞凋亡,Western印迹测NF-κB蛋白表达.结果 HF组较NC组GIR下降、NF-κB表达及β细胞凋亡数目增加,RSG组较HF组GIR升高、NF-κB表达及β细胞凋亡数目减少,与NC组无差异.结论 高脂饮食4w诱导胰岛素抵抗大鼠模型.罗格列酮可能通过降低NF-κB表达而改善胰岛素抵抗,减少胰岛β细胞凋亡.     

核因子-κB在脑缺血预处理中的作用

脑缺血预处理(brain ischemic conditioning,BIP)可提高脑组织对缺血损伤的耐受性.核因子-κB(nuclear factor of κB,NF-κB)是一种重要的转录调控因子,存在于神经系统的所有类型细胞.研究表明,BIP可能通过介导NF-κB的一系列级联反应而发挥神经保护效应,这可能为BIP在临床上预防和治疗缺血性脑血管病提供新的治疗策略.     

核因子-κB在脂多糖诱导的大鼠胰腺腺泡细胞AR42J炎性效应中的作用

目的 探讨核因子-κB(NF-κB)在急性胰腺炎体外模型中的作用.方法 以10 mg/L脂多糖刺激AR42J细胞构建急性胰腺炎的体外模型,设2 h、6 h、12 h、18 h和24 h共5个时间点,每时间点设3个复孔,逆转录-多聚酶链反应(RT-PCR)半定量法观察细胞间黏附分子-1(ICAM-1)和NF-κB p65亚单位mRNA表达的改变;链酶亲和素-生物素-过氧化物酶复合物法(SABC)检测p65蛋白在AR42J细胞中的表达;人工碘比色法观察培养液上清中淀粉酶的改变.结果 脂多糖刺激后,AR42J细胞以时间依赖方式上调ICAM-1 mRNA和p65 mRNA的表达,24 h达最高值;二者之间具有直线相关性(P＜0.01),同时p65蛋白亦呈时间依赖方式表达增强,24 h表达最强;各组间淀粉酶无明显改变(P＞0.05).结论 在脂多糖诱导的胰腺腺泡细胞AR42J炎性效应中,NF-κB调控致炎细胞因子ICAM-1的表达.     

核因子-κB在急性胰腺炎病程中的研究进展

核因子-κB(NF-κB)是一种具有多向性调节作用的核转录因子,可在免疫刺激剂等多种因素作用下被激活,参与调节免疫功能、炎症、凋亡有关的基因转录与表达,NF-κB在多种疾病中的作用已日益引起人们的关注。近年研究证实,NF-κB在急性胰腺炎病程中发挥着重要的作用。     

核因子-κB与酒精性肝病

本文总结了NF-κB在酒精性肝病发生发展中所起的作用:可促进炎症反应和氧化应激,同时还有促进肝细胞再生和抗凋亡作用,针对NF-κB活性的激活与抑制,可以从不同环节寻找药物用于治疗和预防酒精性肝病。     

核因子-κB与动脉粥样硬化

<正>核因子(NF)-κB是属于Rel家族的转录因子,是与诸多包括动脉粥样硬化(AS)在内炎症性疾病密切相关的细胞内信号转导通路。在AS发展的各个阶段,从斑块形成到稳定和破裂,活化的NF-κB通过调节下游如细胞因子、炎症介质、趋化因子等参与AS的信号转导。1 NF-κB通路的组成1.1 NF-κB家族转录因子NF-κB是1986年首次在成熟的B淋巴细胞核提取时发现的,能与免疫球蛋白kappa(k)轻链上的     

NF-κB生物学特性及其在胰腺疾病中的表达研究

NF-κB是一种具有多向调节作用的可诱导的转录因子,分布广泛,功能复杂。研究显示,NF-κB异常活化在胰腺多种疾病发生、发展过程中发挥重要作用。NF-κB亦可作为分子靶点,抑制其活性将成为胰腺疾病防治的新思路。本文概述NF-κB的生物学特性及其在胰腺疾病中的表达和意义。     

核因子-κB在大鼠急性坏死性胰腺炎中作用的实验研究

目的了解核因子-κB在大鼠实验性急性坏死性胰腺炎中作用。方法32只SD大鼠随机分为假手术组,急性坏死性胰腺炎(ANP)组。用凝胶迁移滞留方法检测每组大鼠6h,12h胰腺组织核因子-κBDNA结合活性的变化,并观察胰腺病理,血清淀粉酶,血清TNF-α改变。结果同假手术组相比,ANP组的胰腺病理评分,血清淀粉酶,TNF-α,胰腺组织核因子-κB活性明显升高(P<0.01),另外在ANP组内术后12h的大鼠胰腺病理评分,血清TNF-α,胰腺组织核因子-κB活性比6h组升高更为明显。结论核因子-κB在大鼠ANP时存在着动态变化,且调控着血清TNF-α的表达,从而参与了ANP的发病机制。     

核因子-κB在大鼠急性坏死性胰腺炎中作用的实验研究

目的了解核因子-κB在大鼠实验性急性坏死性胰腺炎中作用.方法 32只SD大鼠随机分为假手术组,急性坏死性胰腺炎(ANP)组.用凝胶迁移滞留方法检测每组大鼠6 h,12 h胰腺组织核因子-κB DNA结合活性的变化,并观察胰腺病理,血清淀粉酶,血清TNF-α改变.结果同假手术组相比,ANP组的胰腺病理评分,血清淀粉酶,TNF-α,胰腺组织核因子-κB活性明显升高(P＜ 0.01),另外在ANP组内术后12 h的大鼠胰腺病理评分,血清TNF-α,胰腺组织核因子-κB活性比6 h组升高更为明显.结论核因子-κB在大鼠ANP时存在着动态变化,且调控着血清TNF-α的表达,从而参与了ANP的发病机制.     

Liraglutide及PTEN在高脂饮食诱导的大鼠胰岛细胞凋亡中的作用

目的观察高脂饮食的SD大鼠胰腺第10号染色体同源丢失性磷酸酶-张力蛋白基因（PTEN）表达量的变化,以及liraglutide对胰岛细胞凋亡的作用。方法20只雄性SD大鼠随机分为3组：正常饮食（ND）组（n=6）、高脂饮食（HFD）组（n=6）和高脂饮食并给予liraglutide（HL）组（n=8）。ND组给予正常饮食,HFD组和HL组给予高脂饮食持续20周后行0GTT试验。随后ND组和HFD组给予生理盐水0．2mg／kg,HL组给予liraglutide0．2mg／kg,早晚各1次,持续4周,给药终点再次行OG-TT试验,评估β细胞功能。应用实时定量PCR检测各组大鼠胰腺PTENmRNA相对表达量,TUNEL染色观察大鼠胰岛细胞凋亡的变化。结果与ND组相比,HFD组和HL组大鼠体重增加（P〈0．05）,血TG和TC升高（P〈0．01）,OGTT中胰岛素曲线下面积（AUCIns）增大（P〈0．05或P〈0．01）,且胰腺PTENmRNA表达量增多（P〈0．05）。与HFD组相比,HL组体重、进食量和血TC下降（P〈0．05或P〈0．01）,OGTT中60min和120min时胰岛素和血糖降低（P〈O．01）,胰岛细胞凋亡减少,β细胞功能得到一定改善,但胰腺PTENmRNA表达量的差异无统计学意义（P〉0．05）。结论高脂饮食时SD大鼠胰腺PTENmRNA表达增加,liraglutide对高脂饮食大鼠胰腺PTENmRNA表达没有影响,但可能通过Akt信号通路减少其胰岛细胞凋亡。     

Role of osteoprotegerin/receptor activator of nuclear factor kappa B/receptor activator of nuclear factor kappa B ligand axis in nonalcoholic fatty liver disease

Concomitantly with the increase in the prevalences of overweight/obesity, nonalcoholic fatty liver disease(NAFLD) has worldwide become the main cause of chronic liver disease in both adults and children. Patients with fatty liver display features of metabolic syndrome(Met S), like insulin resistance(IR), glucose intolerance, hypertension and dyslipidemia. Recently, epidemiological studies have linked obesity, Met S, and NAFLD to decreased bone mineral density and osteoporosis, highlighting an intricate interplay among bone, adipose tissue, and liver. Osteoprotegerin(OPG), an important symbol of the receptor activator of nuclear factor-B ligand/receptor activator of nuclear factor kappa B/OPG system activation, typically considered for its role in bone metabolism, may also play critical roles in the initiation and perpetuation of obesityrelated comorbidities. Clinical data have indicated that OPG concentrations are associated with hypertension, left ventricular hypertrophy, vascular calcification, endothelial dysfunction, and severity of liver damage in chronic hepatitis C. Nonetheless, the relationship between circulating OPG and IR as a key feature of Met S as well as between OPG and NAFLD remains uncertain. Thus, the aims of the present review are to provide the existent knowledge on these associations and to discuss briefly the underlying mechanisms linking OPG and NAFLD.     

核因子κB在慢性阻塞性肺疾病发病机制中的作用

核因子κB(nuclear factor kappa B,NF-κB)是一种广泛存在于体内多种细胞的核转录因子,与免疫,肿瘤的发生、发展,细胞凋亡的调节以及胚胎发育等有着密切联系,是一种重要的核转录因子.慢性阻塞性肺疾病(chronic obstructive pulmonary diseases,COPD)是一种以气道、肺实质和肺血管的慢性炎症为特征的疾病.NF-κB作为信号转导途径中的枢纽,活化的失调与COPD的发生和发展密切相关,参与COPD的多种发病机制.本文就NF-κB及其在COPD的中的作用作一综述.     

High glucose induced nuclear factor kappa B mediated inhibition of endothelial cell migration

Delayed wound healing and accelerated atherosclerosis are common vascular complications of diabetes mellitus. Although elevated blood glucose level is the major contributing factor, mechanisms that mediate these complications are not clearly understood. In the present study, we have demonstrated that elevated glucose inhibits endothelial cell migration, thereby delaying wound healing. Our results clearly indicated that high glucose (10 or 30 mM) induced activation of nuclear factor kappa B (NF-kappaB) inhibited endothelial cell migration (P<0.05). High glucose induced NF-kappaB DNA binding activity may mediate this inhibition of migration by regulating intracellular nitric oxide. In vitro wound healing model in human aortic endothelial cells (HAEC) were used to evaluate cell migration under the influence of high glucose. The migration inhibited by high glucose was restored by NF-kappaB inhibitors (including E3-4-methylphenyl sulfonyl-2-propenenitrile, N-tosyl-Lys-chloromethylketone (TLCK), or over-expression of inhibitor subunit of kappaB) and endothelial nitric oxide synthase inhibitors (N-methyl-L-arginine (L-NMMA); and Nomega-nitro-L-arginine methyl ester (L-NAME)). Furthermore, NF-kappaB inhibitors attenuated high glucose induced eNOS expression and intracellular nitric oxide (NO) production. Cytoskeletal immunofluorescence staining confirmed differences in actin distribution in HAEC incubated in high glucose in the presence or absence of NF-kappaB and NO inhibitors, explaining the differences observed in migration. In summary, our results for the first time suggest therapeutic strategies involving inhibition of NF-kappaB activation induced by high glucose, which may improve wound healing and help avoid some of the vascular complications of diabetes.     

Chitosan ameliorates the severity of steatohepatitis induced by high fat diet in rats

Objective. Currently, no agent has been conclusively demonstrated to prevent the progression of non-alcoholic steatohepatitis (NASH). Chitosan, a natural product derived from chitin, was thought to possess hypocholesterolemic properties. The aim of this study was to evaluate the potential effects of chitosan on nutritional steatohepatitis in rats. Material and methods. Rats were fed with a high fat diet for 4 weeks to develop NASH that was confirmed by liver biopsy, and then 4 weeks of chitosan was given. Serum chemistry and liver histology were assessed and the steatoinflammatory mechanisms were studied. Results. Chitosan significantly protected against high fat diet-induced hepatic steatohepatitis. This effect was associated with repressed serum levels of total protein (TP), globulin (GLO), alanine aminotransferase (ALAT), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT), total cholesterol (TC) and low-density lipoprotein (LDL). Chitosan elevated the serum levels of high-density lipoprotein (HDL) and the ratio of albumin to globulin. Furthermore, increased TNF-α, lipoemia, hyperinsulinemia, hyperleptinemia and hypoadiponectin in NASH were significantly ameliorated by treatment with chitosan. Conclusions. Chitosan effectively attenuated the steatohepatitis induced by a high fat diet. The therapeutic effect of chitosan on NASH may be activated through exerting an influence on adipokines.     

Melatonin inhibits nuclear factor kappa B activation and oxidative stress and protects against thioacetamide induced liver damage in rats

BACKGROUND/AIMS: Free radical-mediated oxidative stress has been implicated in the pathogenesis of acute liver injury. The aim of our study was to investigate whether melatonin, a potent free radical scavenger could prevent fulminant hepatic failure in rats. METHODS: Liver damage was induced by two consecutive injections of thioacetamide (TAA, 300 mg/kg/i.p.) at 24 h intervals. Treatment with melatonin (3 mg/kg/daily, i.p) was initiated 24 h prior to TAA. RESULTS: Twenty-four h after the second TAA injection, serum liver enzymes and blood ammonia were lower in rats treated with TAA+melatonin compared to TAA (P<0.001). Liver histology was significantly improved and the mortality in the melatonin-treated rats was decreased (P<0.001). The increased nuclear binding of nuclear factor kappa B in the livers of the TAA-treated rats, was inhibited by melatonin. The hepatic levels of thiobarbituric acid reactive substances, protein carbonyls and inducible nitric oxide synthase were lower in the TAA+melatonin-treated group (P<0.01), indicating decreased oxidative stress and inflammation. CONCLUSIONS: In a rat model of TAA-induced fulminant hepatic failure, melatonin improves survival and reduces liver damage and oxidative stress. The results suggest a causative role of oxidative stress in TAA-induced hepatic damage and suggest that melatonin may be utilized to reduce liver injury associated with oxidative stress.     

马来酸罗格列酮干预高脂饲养大鼠脂肪肝的研究

目的观察高脂饲养所致正常SD大鼠脂肪肝与胰岛素抵抗的关系及罗格列酮干预脂肪肝的效果。方法将8周龄雄性SD大鼠随机分为三组，每组各11只：正常饲养组（NC）、高脂饲养组（HF）、高脂＋罗格列酮组（HF4-Ros）。饲养8周后取空腹血测定血糖、脂联素，胰岛素敏感性用正常血糖高胰岛素钳夹术稳态时的葡萄糖输注率（GIR）来评价，测定肝脏中TG含量，并对大鼠肝脏组织做HE染色。结果高脂饲养8周后，与NC组相比，HF组肝脏呈现明显脂肪肝，肝脏中TG明显增加达154．2％（NC组3．89mg／g，HF组9．89mg／g，P〈0．01）；与HF组相比，HF4-Ros组肝脏中TG显著降低达46．6％（5．28mg／g，P〈0．01），脂肪肝减轻。结论马来酸罗格列酮能明显改善高脂饲养大鼠的脂肪肝。