Homer1a reduces inflammatory response after retinal ischemia/reperfusion injury

Elevated intraocular pressure(IOP)is one of the causes of retinal ischemia/reperfusion injury,which results in NRP3 inflammasome activation and leads to visual damage.Homerla is repo rted to play a protective role in neuroinflammation in the cerebrum.However,the effects of Homerla on NLRP3inflammasomes in retinal ischemia/reperfusion injury caused by elevated IOP remain unknown.In our study,animal models we re constructed using C57BL/6J and Homer1^(flox/-)/Homerla^(+/-)/Nestin-Cre^(+/-)mice with elevated IOP-induced retinal ischemia/repe rfusion injury.For in vitro expe riments,the oxygen-glucose deprivation/repe rfusion injury model was constructed with M uller cells.We found that Homerla ove rexpression amelio rated the decreases in retinal thickness and Muller cell viability after ischemia/reperfusion injury.Furthermore,Homerla knockdown promoted NF-κB P65^(Ser536)activation via caspase-8,NF-κB P65 nuclear translocation,NLRP3 inflammasome formation,and the production and processing of interleukin-1βand inte rleukin-18.The opposite results we re observed with Homerla ove rexpression.Finally,the combined administration of Homerla protein and JSH-23 significantly inhibited the reduction in retinal thickness in Homer1^(flox/-)Homer1a^(+/-)/Nestin-Cre^(+/-)mice and apoptosis in M uller cells after ischemia/reperfusion injury.Taken together,these studies demonstrate that Homer1a exerts protective effects on retinal tissue and M uller cells via the caspase-8/NF-KB P65/NLRP3 pathway after I/R injury.

Secoemestrin C Ameliorates Psoriasis-like Skin Inflammation in Mice by Suppressing the TNF-α/NF-κB Signaling Pathway

Objective Secoemestrin C(SC),an epitetrathiodioxopiperazine isolated from Aspergillus nidulans,has been previously reported to have immunomodulatory and hepatoprotective effects against acute autoimmune hepatitis.However,the effect of SC on regulating the inflammation and its underlying mechanisms in the pathogenesis of psoriasis remain unclear.This study aimed to evaluate the effects of SC on inflammatory dermatosis both in vitro and in vivo.Methods In vitro,HaCaT cells were induced with tumor necrosis factor-alpha(TNF-α,10 ng/mL)to establish an inflammatory injury model,and the expression of nuclear transcription factor-κB(NF-κB)pathway components was measured using qRT-PCR and Western blotting.An in vivo mouse model of imiquimod(IMQ)-induced psoriasis-like skin inflammation was used to evaluate the effectiveness of SC in alleviating psoriasis.Results SC significantly blocked the activation of NF-κB signaling in TNF-α-stimulated HaCaT cells.In addition,systemic and local administration of SC improved psoriatic dermatitis in the IMQ-induced mouse model.SC reduced skin scale and significantly inhibited the secretion of inflammatory factors in skin lesions.Conclusion The protective effect of SC against psoriatic-associated inflammation reveals its potential therapeutic value for treating psoriasis.

归原疏筋合剂治疗腰椎间盘突出症的临床疗效及对血清NF-κB p65表达水平的影响

【目的】探究归原疏筋合剂治疗腰椎间盘突出症(LDH)患者的临床疗效及其可能的作用机制。【方法】将68例气滞血瘀证LDH患者随机分为试验组和对照组,每组各34例。对照组给予塞来昔布及甲钴胺片内服治疗,试验组在对照组的基础上加用归原疏筋合剂内服治疗,疗程为4周。观察2组患者治疗前后腰痛和下肢痛视觉模拟量表(VAS)评分、Oswestry功能障碍指数(ODI)评分、改良日本骨科协会(JOA)评分以及血清炎症因子[肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)、白细胞介素1β(IL-1β)]和血清核因子κB p65(NF-κB p65)水平的变化情况,并评价2组患者的临床疗效和用药安全性。【结果】(1)脱落情况方面,研究过程中,试验组脱落1例,对照组脱落3例,最终试验组33例、对照组31例纳入疗效统计。(2)疗效方面,治疗4周后,试验组的总有效率为96.97%(32/33),对照组为87.10%(27/31);组间比较(秩和检验),试验组的疗效明显优于对照组(P<0.05)。(3)量表评分方面,治疗后,2组患者的腰痛及下肢痛VAS评分、ODI评分均较治疗前降低(P<0.05或P<0.01),改良JOA评分均较治疗前升高(P<0.01),且试验组对腰痛及下肢痛VAS评分、ODI评分的降低幅度及对改良JOA评分的升高幅度均明显优于对照组(P<0.05或P<0.01)。(4)血清炎症相关指标方面,治疗后,2组患者血清TNF-α、IL-6、IL-1β、NF-κB p65水平均较治疗前降低(P<0.01),且试验组的降低幅度均明显优于对照组(P<0.01)。(5)安全性方面,治疗过程中,试验组的不良事件发生率为2.94%(1/34),对照组为8.82%(3/34),组间比较,差异无统计学意义(P>0.05)。【结论】归原疏筋合剂治疗气滞血瘀证LDH患者疗效确切,可有效缓解患者疼痛症状,改善患者腰椎功能,降低血清炎症因子及NF-κB p65表达水平,其作用机制可能与降低炎症因子水平,抑制NF-κB信号通路的活化有关。

Effects of β-Aescin on the expression of nuclear factor-κB and tumor necrosis factor-α after traumatic brain injury in rats

To investigate the inhibiting effect of β-Aescin on nuclear factor-κB (NF-κB) activation and the expression of tumor necrosis factor-α (TNF-α) protein after traumatic brain injury (TBI) in the rat brain, 62 SD rats were subjected to lateral cortical impact injury caused by a free-falling object and divided randomly into four groups: (1) sham operated (Group A); (2) injured (Group B); (3) β-Aescin treatment (Group C); (4) pyrrolidine dithocarbamate (PDTC) treatment (Group D). β-Aescin was administered in Group C and PDTC treated in Group D immediately after injury. A series of brain samples were obtained directly 6h, 24 h and 3 d respectively after trauma in four groups. NF-κB activation was examined by Electrophoretic Mobility Shift Assay (EMSA); the levels of TNF-α protein were measured by radio-immunoassay (RIA); the water content of rat brain was measured and pathomorphological observation was carried out. NF-κB activation, the levels of TNF-α protein and the water content of rat brain were significantly increased (P＜0.01) following TBI in rats. Compared with Group B, NF-κB activation (P＜0.01), the levels of TNF-α protein (P＜0.01) and the water content of brain (P＜0.05) began to decrease obviously after injury in Groups C and D.β-Aescin could dramatically inhibit NF-κB activation and the expression of TNF-α protein in the rat brain, alleviate rat brain edema, and that could partially be the molecular mechanism by which β-Aescin attenuates traumatic brain edema.

The clinical significance of CD97, NF-kB and COX-2 ingastric MALT lymphomas

Background and Objectives: Increased expression of the CD97, nuclear factor-kB (NF-kB) and cyclooxygenase-2 (COX-2) has been found to play an important role in development of many cancers, including gastric neoplasm. However, the expression and biological behavior of CD97, NF-kB and COX-2 in gastric MALT (mucosa-associated lymphoid tissue) lymphoma has not been well investigated. Methods: The expressions of CD97, COX-2 and NF-kB in 47 cases of gastric MALT lymphoma were detected immunohistochemically, and the relevance between their expressions and the biological behavior was analyzed retrospectively. Results: 1) The expressions of CD97, NF-kB and COX-2 were 87.2%, 36.2% and 48.9%, respectively;2) The difference of CD97 expression between depth of invasion limited in mucosa and submucosa and beyond muscularis propria was significant (100.0% vs. 71.4%, P < 0.01). Moreover, the expression of nuclear CD97 between stage IIE, III, IV and stage I patients showed significant difference (96.4% vs. 73.7%, P < 0.05);3) The expression of NF-kB was significantly correlated with tumor size, depth of invasion and stage;4) The expression of COX-2 was significantly correlated with Helicobacter pylori infection, clinical stage, depth of invasion and tumor size (P < 0.05). Conclusions: Expressions of CD97, NF-κB and COX-2 were correlated with tumor invasion and metastasis in gastric MALT lymphoma.

血必净对创伤弧菌脓毒症大鼠肺组织核因子-KBp65表达作用的研究

目的 观察创伤弧菌脓毒症大鼠肺组织核因子-κB（NF-κB）p65基因及蛋白表达,并探讨血必净对其的干预作用.方法 SD大鼠110只,随机分为正常组（A组,n＝10）、创伤弧菌脓毒症组（B组,n＝50,采用大鼠左下肢皮下注射创伤弧菌悬液制作大鼠创伤弧菌脓毒症模型）和血必净治疗干预组（C组,n＝50,感染后半小时腹腔注射血必净4 mL/kg）.B、C组于染菌后1、6、12、24、48 h活杀（各时间点n=10）,采用逆转录-聚合酶链式反应（RT-PCR） 法、Western blot法和双抗体夹心酶联免疫吸附法（ELISA）分别检测大鼠肺组织NF-κB p65的基因与蛋白表达及IL-10的含量,数据采用单因素方差分析.结果 与A组比较,B组大鼠肺组织创伤弧菌感染后6、12 h NF-κB p65 mRNA表达量与6、12、24和48 h肺组织NF-κB p65蛋白表达量均明显增高 （P〈0.05）;与B组相同时间点比较,C组6 h肺组织NF-κB p65 mRNA表达量与12、24及48 h肺组织NF-κB p65 蛋白表达量明显减少（P〈0.05）; 与A组比较,B组创伤弧菌菌感染12、24和48 h IL-10的含量明显增加（P〈0.05）,与B组相同时间点比较,C组24 h（52.444±9.605）肺组织IL-10的含量明显增高（P〈0.05）;感染后48 h,大鼠肺内血管明显充血,间质水肿并伴炎性浸润,肺泡腔塌陷,血必净干预后,肺组织损伤有所减轻.结论 NF-κB参与了创伤弧菌脓毒症肺损伤过程;血必净能抑制NF-κB p65的表达,从而起到保护创伤弧菌脓毒症大鼠肺组织的作用.

PTEN、P-Akt和NF-κB在中耳胆脂瘤上皮中的表达和意义

目的研究10号染色体缺失张力蛋白磷酸酶(phosphatase and tensin homologue deleted on chromosome ten,PTEN)、磷酸化Akt(P-Akt)及核转录因子-κB(NF-κB)在中耳胆脂瘤上皮中的表达,探讨PI3K(phosphatidylinositol-3-kinase,磷脂酰肌醇-3激酶)-Akt信号通路在中耳胆脂瘤上皮细胞过度增殖机制中的可能作用。方法采用免疫组织化学SP法(辣根酶标记链霉卵白素连接法,streptavidin-peroxidase conjugated method)检测30例中耳胆脂瘤组织标本与15例正常外耳道皮肤标本中PTEN、P-Akt及NF-κB蛋白的表达。结果 PTEN蛋白阳性表达主要定位于上皮细胞核,其在中耳胆脂瘤上皮中阳性表达率为36.7%,明显低于正常外耳道皮肤组的93.3%(P<0.01);P-Akt蛋白阳性表达主要定位于上皮细胞胞质,其在中耳胆脂瘤上皮中阳性表达率为70.0%,明显高于正常外耳道皮肤组的26.7%(P<0.01);NF-κB蛋白阳性表达定位于上皮细胞核,其在中耳胆脂瘤上皮中阳性表达率为63.3%,明显高于正常外耳道皮肤组的20.0%(P<0.01)。在30例中耳胆脂瘤上皮组织中,PTEN分别与P-Akt、NF-κB蛋白的表达之间呈显著负相关(P<0.01),而P-Akt和NF-κB蛋白的表达呈显著正相关(P<0.01)。结论 PTEN、P-Akt和NF-κB在中耳胆脂瘤上皮的异常表达可能在胆脂瘤的发生、发展过程中起重要作用。胆脂瘤上皮中PI3K-Akt信号通路的激活可能参与了胆脂瘤上皮细胞过度增殖机制。

辛伐他汀对急性肺损伤大鼠的保护作用及其机制研究

目的 探讨不同剂量辛伐他汀对脂多糖（LPS）诱导急性肺损伤（ALI）大鼠的保护作用及其机制.方法 50只SD大鼠随机分为对照组、模型组及辛伐他汀干预组T1、T2、T3,每组10只.在LPS注射前24 h和10 min,T1、T2、T3组分别腹腔注射5、10、20 mg/kg辛伐他汀进行预处理.4 h后观察肺组织病理学改变,并行肺损伤评分,检测肺组织核转录因子-SymbolkA@B（NF-SymbolkA@B） p65蛋白及支气管肺泡灌洗液（BALF）中肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）的表达.结果 与模型组比较,T1、T2、T3组肺损伤均显著改善,肺组织NF-SymbolkA@B p65蛋白水平、BALF中TNF-α和IL-1β表达呈一致性显著降低,其中以T3组最显著.NF-SymbolkA@B p65、TNF-α和IL-1β水平与肺损伤评分均呈显著正相关.结论 辛伐他汀对LPS诱导的ALI有保护作用,且与剂量相关,其机制可能与抑制NF-SymbolkA@B活化、降低TNF-α、IL-1β表达有关.

心肌缺血再灌注中肿瘤坏死因子-α表达及与核因子-kB活化的关系

目的 :研究心肌缺血 -再灌注时心肌组织肿瘤坏死因子 -α (TNF -α)表达与心肌核因子 -kB (NF -kB)活化之间的关系。方法 :新西兰兔 2 0 0只分为 :①缺血 -再灌注组 (IR) :结扎兔左冠状动脉前降支造成心肌缺血 4 5min后再开放 ;②吡咯基二硫氨基甲酸酯 (PDTC)预处理组 (IR +PDTC) :在心肌缺血前 1 0分钟静脉注射PDTC (1 5mg/kg) ;③抗肿瘤坏死因子 -α单克隆抗体预处理组 (IR +Anti-TNF -α -mAb) :在心肌缺血前 1 0分钟静脉注射抗肿瘤坏死因子 -α单克隆抗体 ;④假手术对照组 (Sham)。每组又分缺血前 (0 ) ,再灌注后 30、 6 0、90、 1 2 0、 2 4 0、 36 0min时相点。用酶联免疫吸附实验 (ELISA)测定心肌组织中TNF -α的表达 ,凝胶电泳迁移率(ESMA)分析检测心肌组织NF -kB的活性 ,髓过氧化酶法 (MP0 )定量测定心肌组织中浸润的中性粒细胞。结果 :与缺血前比较 ,在缺血 -再灌注组中心肌再灌注 30min后NF -kB活性开始增高 ,1 2 0min达到高峰 ,之后活性有所下降 ,但仍明显高于缺血前 (P <0 0 5 ) ;心肌TNF -α的表达在心肌再灌注 1 2 0min明显增高 (P <0 0 5 ) ,并持续保持在高水平状态 ,并与中性粒细胞浸润升高有相关性 (r=0 76 4 ,P <0 0 5 ) ;在IR +PDTC及IR +Anti-TNF -α-mAb组 ,PDTC、Anti-TNF -

穿心莲内酯对内毒素诱导大鼠急性肺损伤的保护作用及机制的实验研究

目的研究穿心莲内酯（Andro）对内毒素（LPS）诱导的急性肺损伤（ALI）大鼠的保护作用及机制。方法32只健康成年大鼠随机分成四组。生理盐水对照组、穿心莲内酯对照组、内毒素组和穿心莲内酯治疗组。对内毒素组和穿心莲内酯治疗组大鼠通过鼠尾静脉注射LPS（5mg／kg）。给予LPS后3h．6h及12h，对穿心莲内酯对照组和穿心莲内酯治疗组大鼠腹腔注射穿心莲内酯（10mg／kg）。注射LPS后24h收集各组支气管肺泡灌洗液（BALF）及肺组织。检测BALF中肿瘤坏死因子-α（TNF—d）、白细胞介素-1p（IL-1p）及细胞间黏附因子-1（ICAM-1）的浓度；检测肺组织中的丙二醛（MDA）、核转录因子-κB（NF—κB）浓度及髓过氧化物酶（MPO）活性，同时进行动脉血气分析。结果与LPS组比较，穿心莲内酯治疗组TNF-α降低（P〈0．05），而IL-1B和ICAM-1明显降低（P〈0．01）。穿心莲内酯治疗组与LPS组比较，MPO活性降低（P〈0．05），而MDA和NF—KB明显降低（P〈0．01）。穿心莲内酯治疗组与LPS组比较，PaO，明显升高（P〈0．01），pH值升高（P〈0．05），PaCO：降低（P〈0．05）。结论穿心莲内酯通过抑制NF—KB激活对LPS诱导的ALI具有保护作用。

祛浊化痰中药对AS家兔血管成形术后炎性因子表达的影响

目的:观察祛浊化痰中药(通脉颗粒)对高脂饮食兔血管成形术后炎性因子hs-CRP、ICAM-1、NF-KB的影响。方法:选择新西兰大耳白兔50只随机分为空白组、模型组、中药组、西药组、中西药组各10只,通过喂养高脂饲料建立家兔AS模型,8周后造血管内皮球囊拉伤模型,测定hs-CRP含量及各组ICAM-1、NF-KBmRNA表达。结果:通脉颗粒可显著下调高脂饮食兔血管成形术后病灶中hs-CRP含量,且能明显降低家兔血清ICAM-1、NF-KBmRNA表达水平(P<0.05)。结论:通脉颗粒能减少AS斑块内的炎性因子表达,并可抑制血管内皮拉伤后相关炎性因子的表达,以减少AS的形成及防止术后再狭窄。其作用机制可能与调脂、抗炎的作用有关。

桂枝汤和黄连解毒汤对GK大鼠心肌炎症因子及基膜影响的差异研究

目的观察桂枝汤及黄连解毒汤对自发性糖尿病大鼠(GK大鼠)心肌基膜厚度、心肌核因子-κB(NF-κB)、Ⅳ型胶原表达的作用,探讨有关炎症损伤的机制。方法以Wistar大鼠10只作为正常对照组,40只GK大鼠随机分为GK对照组、二甲双胍组、黄连解毒汤组、桂枝汤组,分别以相应药物灌胃给药12周,检测各组血糖、NF-κB、Ⅳ型胶原阳性表达程度及基膜厚度。结果 GK大鼠血糖升高,NF-κB阳性表达增强,Ⅳ型胶原蛋白表达增强,基底膜厚度增加。二甲双胍、黄连解毒汤均可降低GK大鼠血糖(P<0.01)。黄连解毒汤和桂枝汤均能降低NF-κB及Ⅳ型胶原蛋白表达、降低基底膜厚度与GK大鼠对照组比较差异有统计学意义(P<0.01,P<0.05)。在抑制NF-κB阳性表达方面,桂枝汤和黄连解毒汤疗效无统计学意义。在抑制Ⅳ型胶原蛋白表达、降低基底膜厚度方面,桂枝汤作用强于黄连解毒汤(P<0.01,P<0.05)。结论桂枝汤和黄连解毒汤均可以抑制NF-κB阳性表达,抑制Ⅳ型胶原蛋白表达,降低基膜厚度,且桂枝汤优于黄连解毒汤,显示了其调和营卫治法的独特作用。

乙酰化白藜芦醇保护海水淹溺型急性肺损伤的机制研究

目的观察海水淹溺型急性肺损伤（SWD—ALI）的发病机制，验证乙酰化白藜芦醇通过抑制核因子一KB（NF—KB）的表达减轻SWD—ALI。方法32只大鼠分为正常对照组、模型组、乙酰化白藜芦醇预处理组和乙酰化白藜芦醇对照组。模型组和乙酰化白藜芦醇预处理组气管内注入4mL／kg海水，4h后检测肺损伤指标，并用ELISA法检测肺组织中NF—KB的表达量。结果与正常对照相比，模型组大鼠出现明显肺损伤，并伴有炎性细胞浸润和炎性因子的分泌，同时肺组织中NF—KB表达量增高；乙酰化白藜芦醇预处理组吸入海水后肺部损伤明显减轻，NF—KB表达受到抑制。结论NF～KB的促炎机制参与SWD—ALI的发生，乙酰化白藜芦醇能够通过抑制NF—KB表达减轻SWD—ALI。

人肺癌中NF-κBDNA结合活性的意义探讨

目的:观察在肺癌组织中核因子-κB(Nuclearfactor-kappaB,NF-κB)的DNA结合活性,探讨其在肺癌发展中的意义。方法:采用电泳迁移率(Electrophoreticmobilityshiftassay,EMSA)同位素放射自显影的方法分别检测有随访资料的87例肺癌组织中NF-κB的DNA结合活性。结果:NF-κBDNA结合活性在小细胞肺癌组织中高于其它病理类型,在低分化肺癌组织中结合活性较高,在淋巴结转移肺癌组织中结合活性高于无淋巴结转移肺癌组织(P<0.05)。结论:NF-κB的DNA结合活性与肺癌的病理类型、分化程度及是否有淋巴结转移等因素有关。

妇科千金片对盆腔炎模型大鼠血清中TNF-α、NF-κB含量的影响

目的探讨妇科千金片治疗盆腔炎的作用机理。方法选用Wistar大鼠,运用子宫内接种混合菌液制造急性盆腔炎模型。随机分为空白组、假手术组、模型组、妇科千金片低、中、高剂量组、妇炎康组及罗红霉素组,治疗后,用ELISA检测血清肿瘤坏死因子-α(TNF-α)、核因子κB(NF-kB)含量。结果与空白组比较,模型组TNF-α、NF-κB的含量明显升高(P<0.05);与模型组比较,妇科千金片低、中、高剂量组、妇炎康组及罗红霉素组的TNF-α、NF-κB含量明显降低(P<0.05)。结论妇科千金片可能是通过调节血清中TNF-α、NF-κB的含量而发挥抗炎作用。

Zinc-deficient diet aggravates ventilation-induced lung injury in rats

We investigated the effects of zinc deficiency on acute lung injury （ALI） induced by mechanical ventilation. Male Sprague-Dawley rats were fed with a zinc-deficient or zinc-proficient diet for 4 weeks, and then received mechanical ventilation at normal frequency and pressure for 30 min. Total protein, cell count, the number of poly- morphonuclear neutrophil （PMN） in the bronchoalveolar lavage （BAL）, and vascular endothelial growth factor （VEGF） expression in the lung were determined. Activation of nuclear factor-t^B （NF-~cB） was detected by exam- ining the phosphorylation of NF-kB （pNF-kB p65） and the expression of inhibitor of NF-kB （pI-kBa）. Compared to the controls, total cell count and the number of PMNs were significantly increased to 160% and 140%, respec- tively, in zinc-deficient rats treated with ventilation. Activation of NF-kB was significantly increased and VEGF was also increased to three-folds. Zinc deficiency aggravated the inflammatory response in rats and was associated with the overexpression of VEGF in response to mechanical ventilation. Zinc supplementation may be beneficial to zinc-deficient patients during mechanical ventilation.

分子对接与体内验证联合探讨穿山龙复方对痛风模型大鼠TLR4/MyD88/NF-kB信号通路的影响

目的:探讨穿山龙复方对痛风性关节炎(GA)合并高尿酸血症(HUA)模型大鼠Toll样受体4(TLR4)/髓样分化因子88(MyD88)/核转录因子-κB(NF-κB)(TLR4/MyD88/NF-κB)信号通路的影响。方法:先运用分子对接技术预测穿山龙复方中主要活性成分与TLR4/MyD88/NF-κB信号通路相关靶蛋白的分子间相互作用,再建立痛风性关节炎合并高尿酸血症大鼠复合模型进行体内实验验证。将48只雄性SD大鼠分为正常对照组、模型对照组、阳性对照秋水仙碱0.3 mg/kg组及穿山龙复方0.2、0.4、0.8 g/kg组。用尿酸钠、氧嗪酸钾和10%酵母饲料造模的同时,分别给予相应的药物灌胃。7 d后取材,测定踝关节肿胀度;HE染色观察踝关节病理学变化,血清白细胞介素-8(IL-8)、IL-1β、肿瘤坏死因子-α(TNF-α)含量;以Real-timePCR法测定大鼠踝关节中Tlr4、Myd88、Nfkb mRNA表达。结果:分子对接结果表明复方的主要活性成分与TLR4/MyD88/NF-κB信号通路的靶蛋白均有良好的结合活性,其中薯蓣皂苷与TLR4结合活性最强。体内实验结果表明,与正常对照组相比,模型对照组大鼠血尿酸含量以及踝关节损伤程度均显著增加,血清IL-1、IL-8、TNF-α的含量显著升高(P<0.01),踝关节中Tlr4、Myd88、Nfkb mRNA表达显著上调(P<0.01);与模型对照组比较,穿山龙复方各剂量组和秋水仙碱组对GA&HUA复合模型大鼠血尿酸含量以及踝关节损伤程度显著减轻,血清中IL-1β、IL-8、TNF-α的含量显著降低(P<0.01),踝关节中Tlr4、Myd88、Nfkb mRNA表达显著下调(P<0.01)。结论:穿山龙复方可以通过调节TLR4/MyD88/NF-κB信号通路达到抗痛风性关节炎和高尿酸血症的作用。

脂氧素A4对TNF-α诱导的内皮细胞炎症反应的影响

目的:探讨脂氧素A4(LXA4)对肿瘤坏死因子-α(TNF-α)诱导的人肺微血管内皮细胞(HPMECs)炎症相关因子的影响,并初步探讨其可能的机制。方法:实验分为对照组、TNF-α单独刺激组和不同浓度LXA4(5 ng/mL、25 ng/mL、50 ng/mL)预处理组。实时荧光定量PCR检测HPMECs单核细胞趋化蛋白-1(MCP-1)、E-选择素(E-selectin)、白介素-6(IL-6)mRNA表达水平;细胞免疫化学方法定位检测核因子-κB/p65(NF-κB/p65);蛋白质免疫印迹(Western blot)方法检测细胞核内和细胞总蛋白中NF-κB/p65的水平。结果:LXA4可以抑制TNF-α诱导的HPMECs MCP-1、E-selectin、IL-6 mRNA表达的上调;LXA4可以抑制TNF-α引起的HPMECs p65由细胞质向细胞核的转位。结论:LXA4可能通过抑制NF-κB细胞信号通路而抑制血管内皮细胞炎症相关因子的表达,发挥抗炎作用。

铍病大鼠肺组织TNF-α的水平和NF-κB的表达及其意义

目的探讨肿瘤坏死因子-α(TNF-α)及核因子-κB(NF-κB)在铍病发病中的作用。方法采用一次性非暴露式气管注入法染毒建立铍病模型。用酶联免疫吸附法(ELISA)检测肺组织匀浆及支气管肺泡灌洗液(BALF)中TNF-α水平,免疫组化法测定肺组织NF-κB的表达。同时HE染色观察肺组织的大体病理改变。结果大鼠模型组肺组织的病理改变基本符合人类铍病的特点。模型组大鼠肺组织匀浆及BALF中TNF-α水平、肺组织中NF-κB的表达较生理盐水对照组明显升高(P<0·01);且模型组内TNF-α的水平、NF-κB的表达,60d组明显高于20d组(P<0·05)。结论TNF-α和NF-κB相互作用,在铍病的发病机理中起着重要作用,并可作为判定疾病活动性的一项重要参考指标。

抗肿瘤坏死因子-α单克隆抗体对心肌缺血再灌注损伤的保护作用及与核因子KB活化的关系

目的研究抗肿瘤坏死因子-α单克隆抗体(Anti-TNF-αmAb)对心肌缺血再灌注损伤的保护作用及与心肌核因子-kB(NF-kB)活化之间的关系。方法新西兰兔152只分为①缺血-再灌注组;②抗肿瘤坏死因子-α单克隆抗体预处理组;③假手术对照组。用酶联免疫吸附实验测定心肌组织中TNF-α的表达,凝胶电泳迁移率分析检测NF-kB的活性,髓过氧化酶法定量测定心肌组织中浸润的中性粒细胞。结果心肌缺血-再灌注使NF-kB迅速活化;心肌TNF-α的表达也明显增高,其与中性粒细胞浸润升高有相关性(r=0.764,P<0.05);Anti-TNF-α-mAb能抑制NF-kB的活化、减少TNF-α的表达及中性粒细胞浸润。结论心肌缺血-再灌注能刺激心肌NF-kB的活化,活化的NF-kB启动TNF-α的表达而参与缺血-再灌注损伤的发生过程。抗肿瘤坏死因子-α单克隆体对心肌缺血再灌注损伤的保护作用不仅在于直接减少TNF-α,而且可以抑制TNF-α对心肌NF-kB的活化的反馈激活作用。