儿茶素单体在治疗炎症性肠病作用中对NF-κB信号通路的影响

目的探索儿茶素单体表没食子儿茶素没食子酸酯(EGCG)在治疗炎症性肠病(IBD)模型大鼠作用中对NF-κB信号通路的影响。方法将36只健康SD大鼠随机分为正常对照组、模型组、EGCG治疗组,每组12只,以三硝基苯磺酸(TNBS)灌肠制作大鼠IBD模型。灌肠用药2周后,分别用ELISA检测肠组织中PGE2、NO含量;免疫组化检测肠粘膜COX-2、iNOS的蛋白表达;Western Blotting检测大鼠肠粘膜NF-κB p65蛋白水平的变化。结果①模型组肠组织内PGE2、NO含量显著增高。EGCG治疗组大鼠肠组织内PGE2、NO含量与模型组相比显著减少(P=0.000);②模型组肠粘膜组织中COX-2表达明显增强,正常结肠组织未见或少见COX-2蛋白表达。而EGCG灌肠后大鼠肠组织中COX-2的表达显著下降。③模型组肠粘膜组织中iNOS表达明显增强,正常结肠组织未见或少见iNOS蛋白表达。而EGCG灌肠后大鼠肠组织中iNOS的表达显著下降。④正常大鼠肠组织NF-κB p65蛋白水平较低,模型组肠组织内NF-κB p65蛋白水平显著增加。EGCG可显著抑制肠组织内NF-κB p65蛋白水平表达。结论 EGCG可通过降低NF-κB p65蛋白的表达,下调COX-2、iNOS的表达,使其产物PGE2、NO生成减少,从而达到减轻炎症的目的。因此NF-κB可作为EGCG治疗大鼠实验性结肠炎的一个有效的分子"靶点"。     

花色苷对ApoE基因缺陷小鼠炎症信号转导的影响

目的:探讨黑米皮(BRF)花色苷(ANTH)对ApoE基因(ApoE-/-)缺陷小鼠动脉粥样硬化(AS)斑块形成及炎症信号转导的影响。方法:将45只雄性ApoE-/-小鼠随机分为三组:阳性对照组(A组)、花色苷提取后黑米皮组(B组)和黑米皮花色苷组(C组);15只正常小鼠为阴性对照组(D组)。B组和C组分别加入黑米皮花色苷提取物及5%花色苷提取后的黑米皮,饲养20w,取血后处死动物,测定主动脉脂质斑块大小和血液各型NOS水平及NO水平,Western-blot法检测血管壁内ICAM-1及NF-κB表达。结果:C组的主动脉脂质斑块面积大小明显低于A组和B组;C组总一氧化氮合酶(tNOS)水平明显高于A组和B组;C组血清中iNOS水平略有降低,但差异不显著;C组血清cNOS和NO水平显著升高;C组COX-2mRNA、ICAM-1及NF-κB蛋白质表达下降。结论:黑米皮花色苷是黑米皮抗AS的活性成分,其作用机制与抑制NF-κB介导的炎性因子iNOS、COX-2表达及促进血管舒张因子NO生成有关。     

Dietary supplementation with geranylgeraniol suppresses lipopolysaccharide-induced inflammation via inhibition of nuclear factor-κB activation in rats

Purpose

The isoprenoid geranylgeraniol (GGOH) inhibits nuclear factor-kappa B (NF-κB) activation in the liver, yet the mechanism remains unclear. We investigated the modulation and inhibition of lipopolysaccharide (LPS)-induced NF-κB signaling in the liver of rats fed a GGOH-supplemented diet.

Methods

Rats were fed a diet supplemented with or without GGOH for 10 days. Rats were then intraperitoneally injected with 0.5 mg/kg LPS or vehicle (sterilized saline) and fasted for 18 h. Plasma levels of the inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, and the liver damage indicators alanine and aspartate aminotransferases (ALT and AST) were assessed. Liver mRNA and proteins were assayed for changes in NF-κB target genes and signal transduction genes.

Results

Rats fed a high-dose, GGOH-supplemented diet showed significantly lower levels of plasma inflammatory cytokines and ALT and AST activities. In the liver, GGOH significantly suppressed NF-κB activation and mRNA expression of its pro-inflammatory target genes. Furthermore, GGOH supplementation substantially suppressed mRNA expression of signal transducer genes upstream of the IκB kinase complex. Western blotting of liver extracts further demonstrated the substantial decrease in total IL-1 receptor-associated kinase 1 (IRAK1) and TNF receptor-associated factor 6 (TRAF6), leading to lower signal transduction and inhibition of NF-κB after LPS.

Conclusion

A 10-day, high-dose, GGOH-supplemented diet was sufficient to inhibit LPS-induced inflammation and activation of NF-κB in rat livers. GGOH significantly modulated NF-κB signaling molecules, inhibiting its signal transduction and activation in the liver, thus protecting against liver damage.     

Soy protein inhibits inflammation-induced VCAM-1 and inflammatory cytokine induction by inhibiting the NF-κB and AKT signaling pathway in apolipoprotein E–deficient mice

Purpose

Inflammation is a hallmark of many diseases, such as atherosclerosis, autoimmune diseases, obesity, and cancer. Isoflavone-free soy protein diet (SPI^?) has been shown to reduce atherosclerotic lesions in a hyperlipidemic mouse model compared to casein (CAS)-fed mice, despite unchanged serum lipid levels. However, possible mechanisms contributing to the athero-protective effect of soy protein remain unknown. Therefore, we investigated whether and how SPI^? diet inhibits inflammatory responses associated with atherosclerosis.

Methods

Apolipoprotein E knockout (apoE?/?) mice (5-week) were fed CAS or SPI^? diet for 1 or 5 week to determine LPS- and hyperlipidemia-induced acute and chronic inflammatory responses, respectively. Expression of NF-κB-dependent inflammation mediators such as VCAM-1, TNF-α, and MCP-1 were determined in aorta and liver. NF-κB, MAP kinase, and AKT activation was determined to address mechanisms contributing to the anti-inflammatory properties of soy protein/peptides.

Results

Isoflavone-free soy protein diet significantly reduced LPS-induced VCAM-1 mRNA and protein expression in aorta compared to CAS-fed mice. Reduced VCAM-1 expression in SPI^?-fed mice also paralleled attenuated monocyte adhesion to vascular endothelium, a critical and primary processes during inflammation. Notably, VCAM-1 mRNA and protein expression in lesion-prone aortic arch was significantly reduced in apoE?/? mice fed SPI^? for 5 weeks compared with CAS-fed mice. Moreover, dietary SPI^? potently inhibited LPS-induced NF-κB activation and the subsequent upregulation of pro-inflammatory cytokines, including TNF-α, IL-6, IL-1β, and MCP-1. Interestingly, SPI^? inhibited NF-κB-dependent inflammatory responses by targeting I-κB phosphorylation and AKT activation with no effect on MAP kinase pathway. Of the five putative soy peptides, four of the soy peptides inhibited LPS-induced VCAM-1, IL-6, IL-8, and MCP-1 protein expression in human vascular endothelial cells in vitro.

Conclusions

Collectively, our findings suggest that anti-inflammatory properties of component(s) of soy protein/peptides may be a possible mechanism for the prevention of chronic inflammatory diseases such as atherosclerosis.     

Differential effects of high-fat-diet rich in lard oil or soybean oil on osteopontin expression and inflammation of adipose tissue in diet-induced obese rats

Purpose

To examine the effect of different dietary fat types on osteopontin (OPN) expressions and inflammation of adipose tissues in diet-induced obese rats.

Methods

Male Sprague–Dawley rats were randomly assigned to one control group fed standard diet (LF, n = 10) and two high-fat diet groups fed isoenergy diet rich in lard or soybean oil (HL or HS, n = 45 each). Diet-induced obese rats in HL and HS group were then subdivided into two groups either continuously fed high-fat diet or switched to low-fat diet for 8 more weeks. Fasting serum glucose, insulin, and OPN concentrations were assayed and QUICKI was calculated; the expression of OPN, IL-6, IL-10, TNF-α, NF-κB, and F4/80 in adipose tissue was determined.

Results

Both high-fat diets lead to comparable development of obesity characterized by insulin resistance and adipose tissue inflammation. Obese rats continuously fed high-fat diet rich in lard oil exhibited the highest fasting serum insulin level and adipose tissue OPN, F4/80, TNF-α, and NF-κB expression level. In both high-fat diet groups, switching to low-fat diet resulted in less intra-abdominal fat mass, decreased expression of F4/80, TNF-α, and NF-κB, while decreased OPN expression was only observed in lard oil fed rats after switching to low-fat diet.

Conclusions

Reducing diet fat or replacing lard oil with soybean oil in high-fat diet alleviates obesity-related inflammation and insulin resistance by attenuating the upregulation of OPN and macrophage infiltration into adipose tissue induced by high-fat diet.     

番茄红素对高同型半胱氨酸血症大鼠血管内皮功能的影响和机制研究

目的研究番茄红素(Lyc)预防高同型半胱氨酸血症(HHcy)致大鼠动脉粥样硬化(AS)的作用机制。方法50只SD雄性大鼠分为正常对照组(NC),HHcy对照组n(HC),HHcy+低(HL1)、中(HL2)、高剂量Lyc组(HL3)。NC组给予AOAC配方饲料,其余各组则给予在AOAC配方基础上添加3%L-蛋氨酸的饲料。HL1、HL2、HL3组按体重每日分别给予Lyc10、15、20mg/kgbw,实验期12w。分析血清Hcy、NO、一氧化氮合酶(NOS)、内皮素-1(ET-1),丙二醛(MDA)、·OH、H2O2,血管细胞粘附分子-1(VCAM-1)、单核细胞趋化因子-1(MCP-1)、白介素-8(IL-8)含量。处死动物,取腹主动脉做NF-κB测定和病理学检查。结果除了NC组外,HHcy各组大鼠血清Hcy含量均随时间延长而显著提高;HC组NO含量显著低于NC组,而ET-1含量显著高于NC组,HL2和HL3组NO含量显著高于HC组,而ET-1含量则明显低于HC组,各组间NOS含量无明显差异。病理学检查显示,HC组和HL1组主动脉内膜中有泡沫细胞聚集,有脂肪颗粒沉着,HL2组、HL3组和NC组主动脉内膜完整,无泡沫细胞和脂肪颗粒。HC和HL1组血清MDA和H2O2含量显著高于NC组,HL2和HL3组则明显低于HC组,HL2和HL3组H2O2含量还显著低于HL1组。与HC组相比,HL2和HL3组血清·OH含量显著降低;HC组VCAM-1、MCP-1和IL-8含量显著高于NC组,HL1、HL2和HL3组则明显低于HC组;HC组NF-κB的表达显著高于NC组,HL1、HL2和HL3组则明显低于HC组。结论Lyc可以通过直接淬灭活性氧,抑制NF-κB的激活,减少炎性因子的表达,来改善血管内皮功能,阻止AS的发生。     

Inhibition of lipopolysaccharide-induced cyclooxygenase-2 and inducible nitric oxide synthase expression by 4-[(2'-O-acetyl-α-L-rhamnosyloxy)benzyl]isothiocyanate from Moringa oleifera

Moringa oleifera Lamarck is commonly consumed for nutritional or medicinal properties. We recently reported the isolation and structure elucidation of novel bioactive phenolic glycosides, including 4-[(2'-O-acetyl-α-L-rhamnosyloxy)benzyl]isothiocyanate (RBITC), which was found to suppress inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production in lipopolysaccharide-stimulated RAW 264.7 mouse macrophage cells. Inhibitors of proteins such as cyclooxygenase-2 (COX-2) and iNOS are potential antiinflammatory and cancer chemopreventive agents. The inhibitory activity of RBITC on NO production (IC(50) = 0.96 ± 0.23 μM) was greater than that mediated by other well-known isothiocyanates such as sulforaphane (IC(50) = 2.86 ± 0.39 μM) and benzyl isothiocyanate (IC(50) = 2.08 ± 0.28 μM). RBITC inhibited expression of COX-2 and iNOS at both the protein and mRNA levels. Major upstream signaling pathways involved mitogen-activated protein kinases and nuclear factor-κB (NF-κB). RBITC inhibited phosphorylation of extracellular signal-regulated kinase and stress-activated protein kinase, as well as ubiquitin-dependent degradation of inhibitor κBα (IκBα). In accordance with IκBα degradation, nuclear accumulation of NF-κB and subsequent binding to NF-κB cis-acting element was attenuated by treatment with RBITC. These data suggest RBITC should be included in the dietary armamentarium of isothiocyanates potentially capable of mediating antiinflammatory or cancer chemopreventive activity.     

Physiogenomic comparison of human fat loss in response to diets restrictive of carbohydrate or fat

Background

Adipocytes express inflammatory mediators that contribute to the low-level, chronic inflammation found in obese subjects and have been linked to the onset of cardiovascular disorders and insulin resistance associated with type 2 diabetes mellitus. A reduction in inflammatory gene expression in adipocytes would be expected to reverse this low-level, inflammatory state and improve cardiovascular function and insulin sensitivity. The natural products, curcumin and resveratrol, are established anti-inflammatory compounds that mediate their effects by inhibiting activation of NF-κB signaling. In the present study, we examined if these natural products can inhibit NF-κB activation in adipocytes and in doing so reduce cytokine expression.

Methods

Cytokine (TNF-α, IL-1β, IL-6) and COX-2 gene expression in 3T3-L1-derived adipocytes was measured by quantitative real-time PCR (qRT-PCR) with or without TNFα-stimulation. Cytokine protein and prostaglandin E₂ (PGE₂) expression were measured by ELISA. Effects of curcumin and resveratrol were evaluated by treating TNFα-stimulated adipocytes with each compound and 1) assessing the activation state of the NF-κB signaling pathway and 2) measuring inflammatory gene expression by qRT-PCR and ELISA.

Results

Both preadipocytes and differentiated adipocytes express the genes for TNF-α, IL-6, and COX-2, key mediators of the inflammatory response. Preadipocytes were also found to express IL-1β; however, IL-1β expression was absent in differentiated adipocytes. TNF-α treatment activated NF-κB signaling in differentiated adipocytes by inducing IκB degradation and NF-κB translocation to the nucleus, and as a result increased IL-6 (6-fold) and COX-2 (2.5-fold) mRNA levels. TNF-α also activated IL-1β gene expression in differentiated adipocytes, but had no effect on endogenous TNF-α mRNA levels. No detectable TNFα or IL-1β was secreted by adipocytes. Curcumin and resveratrol treatment inhibited NF-κB activation and resulted in a reduction of TNF-α, IL-1β, IL-6, and COX-2 gene expression (IC₅₀ = 2 μM) and a reduction of secreted IL-6 and PGE₂ (IC₅₀ ~ 20 μM).

Conclusion

Curcumin and resveratrol are able to inhibit TNFα-activated NF-κB signaling in adipocytes and as a result significantly reduce cytokine expression. These data suggest that curcumin and resveratrol may provide a novel and safe approach to reduce or inhibit the chronic inflammatory properties of adipose tissue.     

Epigallocatechin gallate attenuates fibrosis,oxidative stress,and inflammation in non-alcoholic fatty liver disease rat model through TGF/SMAD,PI3 K/Akt/FoxO1, and NF-kappa B pathways

Purpose

To investigate the protective mechanisms of an 85 % pure extract of (?) epigallocatechin gallate (EGCG) in the development of fibrosis, oxidative stress and inflammation in a recently developed dietary-induced animal model of non-alcoholic fatty liver disease (NAFLD).

Methods

Female Sprague–Dawley rats were fed with either normal rat diet or high-fat diet for 8 weeks to develop NAFLD. For both treatments, rats were treated with or without EGCG (50 mg/kg, i.p. injection, 3 times per week). At the end, blood and liver tissue samples were obtained for histology, molecular, and biochemical analyses.

Results

Non-alcoholic fatty liver disease (NAFLD) rats showed significant amount of fatty infiltration, necrosis, fibrosis, and inflammation. This was accompanied by a significant expressional increase in markers for fibrosis, oxidative stress, and inflammation. TGF/SMAD, PI3 K/Akt/FoxO1, and NF-κB pathways were also activated. Treatment with EGCG improved hepatic histology (decreased number of fatty score, necrosis, and inflammatory foci), reduced liver injury (from ~0.5 to ~0.3 of ALT/AST ratio), attenuated hepatic changes including fibrosis (reduction in Sirius Red and synaptophysin-positive stain) with down-regulation in the expressions of key pathological oxidative (e.g. nitrotyrosine formation) and pro-inflammatory markers (e.g. iNOS, COX-2, and TNF-α). EGCG treatment also counteracted the activity of TGF/SMAD, PI3 K/Akt/FoxO1, and NF-κB pathways. Treatment with EGCG did not affect the healthy rats.

Conclusions

Epigallocatechin gallate (EGCG) reduced the severity of liver injury in an experimental model of NAFLD associated with lower concentration of pro-fibrogenic, oxidative stress, and pro-inflammatory mediators partly through modulating the activities of TGF/SMAD, PI3 K/Akt/FoxO1, and NF-κB pathways. Therefore, green tea polyphenols and EGCG are useful supplements in the prevention of NAFLD.     

Silibinin Inhibits Tumor Promotional Triggers and Tumorigenesis Against Chemically Induced Two-Stage Skin Carcinogenesis in Swiss Albino Mice: Possible Role of Oxidative Stress and Inflammation

Silibinin is a major bioactive flavonolignan present in milk thistle (Silybum marianum) that possesses antioxidant, antiinflammatory, and anticarcinogenic activity. However, the precise underlying mechanism remains to be elucidated. The present study was designed to investigate underlying molecular mechanism for antitumorigenic potential of silibinin against chemically induced skin tumorigenesis in Swiss albino mice. In light of the important role of nuclear factor-kappaB (NF-κB), cyclooxygenase-2 (COX-2), iNOS, proinflammatory cytokines, vascular endothelial growth factor, and oxidative stress in carcinogenesis, chemopreventive efficacy of silibinin against 7, 12-dimethylbenz[a]anthracene/12-O-tetradecanoylphorbol-13-acetate-induced 2-stage skin carcinogenesis was studied in terms of cytoprotective enzymes activity, lipid peroxidation, inflammatory responses, and the expression of various molecular marker in skin tissue. We found that topical application of silibinin at the dose of 9 mg/mouse effectively suppressed oxidative stress and deregulated activation of inflammatory mediators and tumorigenesis. Thus, findings of the present study suggest that the chemopreventive effect of silibinin is associated with upregulation of endogenous cytoprotective machinery and down regulation of inflammatory mediators (nitric oxide, tumor necrosis factor-α, interleukin-6, interleukin -1β, COX-2, iNOS, and NF-κB).     

小鼠动脉粥样硬化斑块中RGS5等基因的表达改变及黄芩素干预的实验研究

目的观察黄芩素对小鼠动脉粥样硬化(AS)模型斑块内RGS5等基因表达的影响。方法选用APOE-/-小鼠30只,体重18～22 g,随机分别对照组、模型组和干预组,每组10只,对照组给予APOE-/-普通饮食,模型组以高脂饲料喂养,干预组在高脂饮食中添加黄芩素(0.5%)。造模给药12周后,检测血脂,用Real Time-PCR方法检测对照组、模型组和用药组主动脉壁粥样硬化斑块中RGS5、PPARδ、MCP-1、NF-κB mRNA的表达。结果模型组血脂升高,斑块中RGS5 mRNA表达下调,PPARδ、MCP-1、NF-κB mRNA表达升高(P0.01)。黄芩素降低了高脂血症并逆转了上述基因表达,延缓了AS进程,差异均具有统计学意义(P0.05)。结论 RGS5等基因在AS的进程中具有重要的调控作用,黄芩素通过降低RGS5的表达,延缓AS的发生。     

Inhibition of Lipopolysaccharide-Induced Cyclooxygenase-2 and Inducible Nitric Oxide Synthase Expression by 4-[(2′-O-acetyl-α-L-Rhamnosyloxy)Benzyl]Isothiocyanate from Moringa oleifera

Moringa oleifera Lamarck is commonly consumed for nutritional or medicinal properties. We recently reported the isolation and structure elucidation of novel bioactive phenolic glycosides, including 4-[(2′-O-acetyl-α-L-rhamnosyloxy)benzyl]isothiocyanate (RBITC), which was found to suppress inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production in lipopolysaccharide-stimulated RAW 264.7 mouse macrophage cells. Inhibitors of proteins such as cyclooxygenase-2 (COX-2) and iNOS are potential antiinflammatory and cancer chemopreventive agents. The inhibitory activity of RBITC on NO production (IC₅₀ = 0.96 ± 0.23 μM) was greater than that mediated by other well-known isothiocyanates such as sulforaphane (IC₅₀ = 2.86 ± 0.39 μM) and benzyl isothiocyanate (IC₅₀ = 2.08 ± 0.28 μM). RBITC inhibited expression of COX-2 and iNOS at both the protein and mRNA levels. Major upstream signaling pathways involved mitogen-activated protein kinases and nuclear factor-κB (NF-κB). RBITC inhibited phosphorylation of extracellular signal-regulated kinase and stress-activated protein kinase, as well as ubiquitin-dependent degradation of inhibitor κBα (IκBα). In accordance with IκBα degradation, nuclear accumulation of NF-κB and subsequent binding to NF-κB cis-acting element was attenuated by treatment with RBITC. These data suggest RBITC should be included in the dietary armamentarium of isothiocyanates potentially capable of mediating antiinflammatory or cancer chemopreventive activity.     

Supplementation of broccoli or Bifidobacterium longum–fermented broccoli suppresses serum lipid peroxidation and osteoclast differentiation on alveolar bone surface in rats fed a high-cholesterol diet

High-cholesterol diet enhances osteoclastic activity on alveolar bone by increasing serum lipid peroxidation. We hypothesized that supplementation with dietary antioxidants, such as found in broccoli and its fermented products, might suppress increases in serum lipid peroxidation, contributing to the inhibition of osteoclastic activity after high-cholesterol diet intake. The purpose of the present study was to investigate the effects of broccoli and fermented broccoli consumption on serum lipid peroxidation and osteoclast differentiation in alveolar bone of rats fed a high-cholesterol diet. In this 12-week study, rats were divided into 4 groups (n = 6/group): a control group (fed regular diet) and 3 experimental groups (fed a high-cholesterol [1% wt/wt] diet, or a high-cholesterol diet supplemented with either broccoli powder [5% wt/wt] or Bifidobacterium longum–fermented broccoli powder [5% wt/wt]). Serum hexanoyl-lysine (HEL) levels were measured as a parameter of lipid peroxidation. The number of tartrate-resistant acid phosphatase (TRAP)–positive osteoclasts in alveolar bone was enumerated to evaluate osteoclast differentiation. When compared with regular diet, the high-cholesterol diet increased serum HEL levels and resulted in a higher number of TRAP-positive osteoclasts at 12 weeks. The high-cholesterol diet supplemented with broccoli or B. longum–fermented broccoli showed lower levels of serum HEL and fewer TRAP-positive osteoclasts than the high-cholesterol diet at 12 weeks. In conclusion, consumption of broccoli, or its fermented product, inhibited the effects of a high-cholesterol diet on osteoclast differentiation in rat alveolar bone by suppressing serum lipid peroxidation.     

Zinc Deficiency Induces Vascular Pro-Inflammatory Parameters Associated with NF-κB and PPAR Signaling

Objectives: Marginal intake of dietary zinc can be associated with increased risk of cardiovascular diseases. In the current study we hypothesized that vascular dysfunction and associated inflammatory events are activated during a zinc deficient state.

Design: We tested this hypothesis using both vascular endothelial cells and mice lacking the functional LDL-receptor gene.

Results: Zinc deficiency increased oxidative stress and NF-κB DNA binding activity, and induced COX-2 and E-selectin gene expression, as well as monocyte adhesion in cultured endothelial cells. The NF-κB inhibitor CAPE significantly reduced the zinc deficiency-induced COX-2 expression, suggesting regulation through NF-κB signaling. PPAR can inhibit NF-κB signaling, and our previous data have shown that PPAR transactivation activity requires adequate zinc. Zinc deficiency down-regulated PPARα expression in cultured endothelial cells. Furthermore, the PPARγ agonist rosiglitazone was unable to inhibit the adhesion of monocytes to endothelial cells during zinc deficiency, an event which could be reversed by zinc supplementation. Our in vivo data support the importance of PPAR dysregulation during zinc deficiency. For example, rosiglitazone induced inflammatory genes (e.g., MCP-1) only during zinc deficiency, and adequate zinc was required for rosiglitazone to down-regulate pro-inflammatory markers such as iNOS. In addition, rosiglitazone increased IκBα protein expression only in zinc adequate mice. Finally, plasma data from LDL-R-deficient mice suggest an overall pro-inflammatory environment during zinc deficiency and support the concept that zinc is required for proper anti-inflammatory or protective functions of PPAR.

Conclusions: These studies suggest that zinc nutrition can markedly modulate mechanisms of the pathology of inflammatory diseases such as atherosclerosis.     

COX-2、NF-κB和survivin在肺腺癌组织中表达及意义

目的探讨环氧合酶2(COX-2)、NF-κB和survivin在肺腺癌组织中表达及比较与癌旁组织不同的凋亡情况。方法应用逆转录聚合酶链反应(RT-PCR)检测NF-κB、COX-2和survivin在肺腺癌组织mRNA的表达,westernblot技术检测其蛋白的表达,流式细胞仪检测凋亡情况。结果肺腺癌组织中COX-2、NF-κB和survivinmRNA表达水平显著高于癌旁组织(P<0.05),肺腺癌组织中COX-2、NF-κB和survivin蛋白表达显著高于癌旁组织(P<0.05)。癌旁组织的凋亡率为7.84±1.02%,显著高于对照组2.51±0.35(P<0.05)。结论肺腺癌中NF-κB的高表达与COX-2的高表达有关,COX-2和survivin的高表达抑制组织凋亡,其可能在肺腺癌的发生发展中起重要作用。     

米非司酮对孕7～9周人胎盘绒毛核因子-κB及环加氧酶的影响

目的:观察米非司酮对妊娠7～9周人胎盘绒毛中核因子(NF)-κB及环加氧酶COX表达的影响,探讨其药物流产机理。方法:采用免疫组化法检测NF-κB、COX-1及COX-2在米非司酮药物流产组与负压吸宫对照组(均孕7～9周各12例)胎盘绒毛中的表达。结果:NF-κB和COX-2在药物流产组滋养细胞中阳性表达均较对照组强(均P<0.01);COX-1在两组表达无明显差别(P>0.05)。结论:米非司酮用于人孕7～9周药物流产时,可通过激活核转录因子NF-κB使COX-2表达增多,进而可能通过影响前列腺素的合成等作用产生不利于妊娠的结果。