非诺贝特对高胆固醇血症兔肿瘤坏死因子α和纤溶酶原激活物抑制剂-1的影响

目的 观察非诺贝特对高固醇血症兔血浆肿瘤坏死因子α(TNF-α)、纤溶酶原激活物抑制剂-1(PAI-1)浓度和脂肪组织PAI-1 mRNA表达的影响.方法 15只新西兰大白兔随机分为对照(C)组、高胆固醇血症(A)组和非诺贝特治疗(B)组.ELISA法测定0、8和12周时血浆TNF-α、PAI-1浓度;第12周末取兔皮下脂肪组织,用半定量逆转录多聚酶链反应(RT-PCR)检测PAI-1 mRNA的表达.结果 A组兔脂肪组织PAI-1 mRNA表达升高(P＜0.01),而B组显著减少(P＜0.01);A组兔TNF-α和PAI-1血浆浓度均明显升高(P＜0.01),B组非诺贝特治疗4周,TNF-α浓度降低47.8%(P＜0.05),PAI-1浓度降低51.92%(P＜0.05);实验各阶段血浆PAI-1与TNF-α浓度呈正相关(r=0.997,P＜0.05),TNF-α浓度与总胆固醇(TC,r=0.54,P＜0.05)、低密度脂蛋白胆固醇(LDL-C,r=0.46,P＜0.05)明显相关;血浆PAI-1浓度与脂肪组织PAI-1 mRNA表达无明显相关.结论 非诺贝特能降低高胆固醇血症兔TNF-α和PAI-1血浆浓度,抑制脂肪组织PAI-1 mRNA表达;血浆PAI-1与TNF-α浓度呈正相关.     

小剂量非诺贝特长期治疗冠心病合并高甘油三酯血症

高胆固醇血症早已确认系冠状动脉粥样硬化性心脏病(ＣＨＤ)的独立危险因子。近年来新的流行病学研究证实高甘油三酯血症也是ＣＨＤ独立的危险因子[1] 。可见血脂紊乱为ＣＨＤ的主要危险因素之一 ,长期控制血脂水平 ,可以减缓ＣＨＤ的发生与发展。临床上单用贝特类药物可降低高甘油三酯 (ＴＧ) 4 0 %左右。我们应用小剂量非诺贝特、血脂康长期治疗ＣＨＤ合并ＴＧ血症 ,疗效较好。1　资料与方法1.1　对象　参考ＷＨＯ诊断标准 ,选择 1996年 1月～ 2 0 0 0年 12月门诊ＣＨＤ患者 ,共 6 2例 ,随机分为非诺贝特血脂康联用组 30例 ,男 18例 ,女 12…     

非诺贝特对缺血性脑血管疾病病人血清脂质成分的影响

探索非诺贝特对缺血性脑血管疾病病人血脂成分的影响。方法：缺血性脑血管疾病伴血清脂质成分异常病人５４例（男性３２例，女性２２例；年龄５４±ｓ１２ａ）。非诺贝特０．１ｇ，ｐｏ，ｔｉｄ，４ｗｋ为一个疗程。结果：治疗后血清ＨＤＬ－ｃｈ及ＨＤＬ２－ｃｈ，ＨＤＬ３－ｃｈ明显提高（Ｐ〈０．０１或Ｐ〈０．０５），其升高的产生的总有效率，依次为１００％，９６％及７７％，ＴＣ，ＴＧ及ＬＤＬ－ｃｈ显下降（Ｐ〈０．０１     

微粒化非诺贝特与非诺贝特治疗Ⅱ型糖尿病合并高脂血症的比较

目的：观察微粒化非诺贝特（micronised feofibrate,MF)与非诺贝特（fenofibrate,F)治疗II型糖尿病（non-insulin dependent mellitus,NIDDM)合并高脂血症的疗效,方法：40例（男性25例,女性15例,年龄54a(6a)NIDDM病人用MF胶囊治疗,0．2g,Po,qd*8wk,另35例（男性23例,女性12例,年龄53a(7a)NIDDM病人用F胶囊,0．1g,po,tid*8wk,结果：MF组降低TC,TG,LDL－C分别为9．4％,50．0％,17．3％,升高HDL－C20．4％,F组降低TC,TG,LDL－C分别为18．1％,41．0％,13．5％,升高HDL－C14．9％,结论：MF治疗NIDDM合并高脂血症病人比F更有效。     

非诺贝特治疗高甘油三酯症和高尿酸症的疗效

目的：探讨非诺贝特片治疗高血压病合并高甘油三酯血症和高尿酸血症的疗效。方法：原发性高血压病1～2级伴甘油三酯≥2．3mmol·L^-1患者151例,其中合并高尿酸血症83例,依高血压病合并高甘油三酯血症病例随机分组。对照组维生素B1片10mg,po,tid;治疗组非诺贝特片100mg,po,tid,均连续服药3个月。服药前及服药期满时各取静脉血栓查甘油三酯及尿酸。结果：对照组中,甘油三酯在服药后比服药前下降,差异有统计学意义（P〈0．05）;尿酸服药后比服药前有明显下降,差异有统计学意义（P〈0．05）。治疗组中,甘油三酯和尿酸在服药后比服药前均有明显下降,P〈0．001。观察组与治疗组服药后比较,后者的TG及UA降低程度较前者更明显P〈0．01。结论：非诺贝特片治疗高血压病合并高甘油三酯血症及高尿酸血症,具有治疗周期短、疗效好的特点。     

非诺贝特治疗原发性高脂血症的临床观察

随着生活水平的逐步提高 ,高脂血症的发病率逐渐上升 ,且有向年轻化发展趋势。我们采用非诺贝特治疗原发性高脂血症患者 42例 ,疗效显著 ,且不良反应发生率较低。1　资料与方法1 .1病例选择　本院内科自 1 999年 4月至 2 0 0 0年 7月治疗高脂血症患者 82例 ,随机分为 2组 ,治疗组 42例 (男 2 8,女 1 4) ,年龄 36～ 68(53.6±9.2 5) y;对照组 40例 (男 2 4 ,女 1 6) ,年龄 37～ 67(53.1± 8.65) y。观察期间避免高脂及高碳水化合物的普通饮食 ,2 wk内采血 2次 ,采用 GPO- PAP法 ,两次血清胆固醇 (TC)均≥ 5.70 mmol/L或血清三酰甘油 (TG…     

非诺贝特对肾移植后高脂血症环孢素浓度影响

目的观察苯氧芳酸类降脂药物非诺贝特对肾移植患者血脂代谢和环孢素（CsA）浓度、尿酸水平的影响。方法56例高脂血症的肾移植患者服用微粒化的非诺贝特200mg/d,一个月后观察其血脂、尿酸水平和CsA浓度的改变。结果治疗一个月后所有患者甘油三酯（TG）和总胆固醇（T-CHOL）均降低,TG降低更为明显,同时高密度脂蛋白（HDL）水平升高,但低密度脂蛋白（LDL）降低没有统计学意义。CsA浓度用药前后无明显改变,尿酸水平降低。结论非诺贝特可显著改善肾移植患者的高TG血症,且对环孢素浓度影响不大。对高尿酸血症患者有降低尿酸作用。     

不同剂型非诺贝特对高血脂大鼠血脂水平的影响

目的　比较微粉化非诺贝特与标准化非诺贝特的降血脂作用。方法　用高脂饲料喂养Wistar大鼠 ,导致大鼠高脂血症 ,然后分别给予微粉化非诺贝特每天 2 0、30、40mg·kg- 1 及标准化非诺贝特每天 2 0、30、40、60、80mg·kg- 1 。于实验d 1 0取血清测定TC、TG。结果　①相同实验条件下 ,微粉化非诺贝特胶囊降低高血脂大鼠血清TC和TG的最低有效剂量为每天 30mg·kg- 1 ,而标准化非诺贝特胶囊为每天 80mg·kg- 1 ;②两种剂型非诺贝特在有效剂量下 ,可使高血脂大鼠的TG水平降至正常 ,使高血脂大鼠的TC水平下降 36 69%～ 51 56 %。结论　微粉化非诺贝特优于标准化非诺贝特制剂 ,非诺贝特对血脂的调节以降低血清TG为主 ,尚能降低血清TC水平     

非诺贝特治疗原发性高脂血症的临床观察

目的观察非诺贝特的调脂作用。方法给原发性高脂血症患者78例服用非诺贝特,观察用药前后血脂水平及肝功能、血糖的变化。结果患者用药8周后甘油三酯和总胆固醇明显下降,高密度脂蛋白升高;肝功能、血糖地无明显变化。结论非诺贝特是一种安全、有效的调脂药物。     

Role of tumor necrosis factor-alpha in the development of spontaneous hepatic toxicity in Long-Evans Cinnamon rats

The objective of this study was to evaluate the potential role of TNF-alpha in the onset of acute hepatitis in the Long-Evans Cinnamon (LEC) rat, an animal model for inherited copper (Cu) toxicosis. In LEC rats, Cu is accumulated in the liver with age, and clinical signs of acute hepatitis were observed as, icterus, reduced body weight, nasal bleeding, dehydration, and reduced food intake at 12 weeks of age. Cellular changes such as apoptosis in the liver were evident in these rats with increasing age. Positive TNF-alpha and TNFR1 immunostainings were observed in hepatocytes and Kupffer cells in LEC rats. Hepatic levels of caspase-3 activity, TNF-alpha mRNA, and protein were also increased in LEC rats from 6 to 12 weeks of age as compared with control Long-Evans (LE) rats. The neutralization of TNF-alpha by passive immunization or the inhibition of caspase activity can block the apoptotic process initiated by TNF-alpha. In this study, we evaluated the effects of passive immunization of LEC rats with weekly administration of anti-rat TNF-alpha on Cu-induced acute hepatitis. This treatment resulted in a reduction of the percentage of apoptotic cells in the liver, decreased activity of caspase-3, and also in down-regulation of the TNF-alpha gene expression. Thus, these results suggest a major role for TNF-alpha on the pathogenesis of Cu-induced acute hepatitis in LEC rats.     

小檗碱对高果糖饲养诱导大鼠胰岛素抵抗和肝脏TNF-α表达的影响

目的研究小檗碱对高果糖饲养诱导胰岛素抵抗大鼠的作用。方法高果糖饲料喂养SD大鼠6wk后,分为3组,模型组,小檗碱组(187.5mg.kg-1.d-1灌服)、二甲双胍组(184mg.kg-1.d-1灌服)作为对照,继续高果糖饮食。实验同时设立正常对照组,普通饮食喂养。4wk后处死大鼠;测定血糖、血清胰岛素、胰岛素抵抗指数及血脂的变化,用RT-PCR方法观察肝脏TNF-αmRNA的表达。结果模型组胰岛素、胰岛素抵抗指数、游离脂肪酸(free fatty acids,FFA)及甘油三酯(triglycerides,TG)水平均明显升高;肝脏TNF-αmRNA的表达与正常对照组比较明显升高。小檗碱降低了胰岛素抵抗大鼠的血糖、血清胰岛素、胰岛素抵抗指数、TG、FFA及TNF-αmRNA的表达。二甲双胍降低了大鼠的血糖、血清胰岛素、胰岛素抵抗指数及TG。结论小檗碱可以改善胰岛素抵抗,其机制可能包括抑制肝脏TNF-αmR-NA的表达与改善脂代谢紊乱。     

肥胖大鼠非酒精性脂肪肝与血清脂联素和肿瘤坏死因子α的关系及吡格列酮干预

目的观察营养性肥胖大鼠非酒精性脂肪肝(NAFLD)与血清脂联素和肿瘤坏死因子α(TNF-α)的关系,以及吡格列酮干预后的变化。方法45只SD♂大鼠随机分为3组:吡格列酮组(P)、高脂对照组(HF)和普通饮食组(NC),各15只。P、HF组给予高脂饮食,NC组给予普通饲料;12wk后,P组行吡格列酮10mg·kg-1.d-1灌胃,HF组和NC组用相应溶剂灌胃,均灌胃4wk。检测血清脂联素、TNF-α、游离脂肪酸(FFA)水平和其他生化指标等,计算Lee′s指数、HOMA-IR指数和肝脏指数,行肝脏病理切片和HE染色。结果与NC组相比,HF组大鼠体重、肝脏指数、FPG、FINS、ALT、HOMA-IR和血清TNF-α水平均明显增高,血清脂联素水平降低(P<0.05),肝细胞出现脂肪变性。与HF组比较,P组大鼠肝脏指数、HOMA-IR、FFA、TNF-α均降低,脂联素水平升高(P<0.05),肝细胞脂肪变性明显改善。HF组大鼠血清FFA、TNF-α与HOMA-IR、肝脏指数正相关,脂联素与之负相关(P<0.05)。结论高脂饮食可引起大鼠营养性肥胖、胰岛素抵抗和NAFLD;吡格列酮能提高胰岛素敏感性,改善脂肪细胞变性,可能与降低TNF-α、升高脂联素有关。     

Increased serum tumor necrosis factor-alpha levels and treatment response in major depressive disorder

RATIONALE: Over the last 15 years, an increasing body of evidence has suggested a causal relationship between depression and the immunological activation and hypersecretion of pro-inflammatory cytokines, such as interleukin-1, interleukin-6 and tumor necrosis factor-alpha (TNF-alpha). However, little is known about the probable relationship of serum TNF-alpha with major depressive disorder (MDD). OBJECTIVE: To assess whether serum TNF-alpha levels could be associated with the clinical course of MDD. SUBJECTS AND METHODS: TNF-alpha and C-reactive protein (CRP) serum concentrations, erythrocyte sedimentation rate, and leukocyte count were measured in 26 MDD patients and in 17 controls. The measurements were repeated following 6 weeks of antidepressant treatment with selective serotonin re-uptake inhibitors. Psychopathological improvement and the severity of depression were evaluated with the Hamilton Depression Rating Scale (HAMD) and Beck Depression Inventory (BDI). RESULTS: On admission, serum TNF-alpha and leukocyte count were significantly higher in MDD patients compared to controls ( P<0.001 and P=0.005, respectively). With the antidepressant treatment, both HAMD and BDI scores decreased significantly (P<0.001 for both). Comparison of pre- and post-treatment measurements revealed that TNF-alpha, CRP, and leukocyte count decreased to levels comparable with those of the control subjects ( P<0.001, P=0.01, and P=0.01, respectively). CONCLUSIONS: The results emphasized that some immunological parameters, such as CRP, leukocyte count and TNF-alpha, are significantly involved in the clinical course and treatment response in MDD. TNF-alpha in particular could be considered as a potential state marker in MDD.     

Tumor necrosis factor-alpha production-regulating activity of phthalimide derivatives in genetically modified murine melanoma cells B78H1

The effect of imides, monothioimides, trimellitimides, as well as 5'-deoxy-5'-phthaloylamino-derivatives of azidothymidine on tumor necrosis factor-alpha (TNF-alpha) production by genetically modified murine B78H1 melanoma cells transduced with the gene for human TNF-alpha (B78/TNF) was investigated. It was found that N-(adamant-1-yl)monothiophthalimide (1e) and N-(adamant-2-yl)-monothiophthalimide (1f) showed over 200% enhancing of TNF-alpha production while some of imides were inhibitors.     

Effect of fenofibrate on serum and tissue sialic acid levels in short-term experimental hypercholesterolemia

In recent years, sialic acid is considered to be a possible marker for cardiovascular diseases. The aim of this study was to investigate the effect of two different treatment periods of fenofibrate (CAS 49562-28-9) on serum, heart and liver sialic acid levels in experimental hypercholesterolemia. Serum, heart and liver total sialic acid levels were determined by Warren's thiobarbituric acid (TBA) method and serum lipid levels by commercial kits at the end of the fenofibrate treatment for 3 and 6 weeks. Fenofibrate treatment reduced serum total sialic acid levels significantly in the control and hypercholesterolemic groups at the end of the 3rd week and only in the control group at the end of the 6th week. Serum sialic acid levels of fenofibrate-treated hypercholesterolemic rats in the 6-week period were significantly higher than those in the 3-week period. Neither the hypercholesterolemic diet nor fenofibrate had any significant effect on heart and liver sialic acid levels. In conclusion, decreased serum sialic acid levels in control and hypercholesterolemic groups by fenofibrate short-term treatment may contribute to the decreased risk of cardiovascular diseases that accompanies the hypercholesterolemic complications. The decreased serum sialic acid levels further indicate the clinical efficacy of fenofibrate as an anti-inflammatory agent.     

肿瘤坏死因子α在妊娠不同时期及老化胎盘组织中的表达及意义

目的探讨肿瘤坏死因子α（TNF—α）在妊娠不同时期胎盘组织中的表达变化及与胎盘老化的相关性。方法取早、中、晚各期和老化的胎盘组织，采用免疫组化的方法检测胎盘中TNF—α的表达和分布情况。结果TNF-α早孕组与晚孕组、老化组表达差异有统计学意义（P〈0．05）；中孕组与晚孕组、老化组表达差异亦有统计学意义（P〈0．05）；晚孕组与老化组的表达差异无统计学意义（P〉0．05）。结论TNF-α可能在胎盘老化过程中发挥重要作用。     

Salicylate blocks lipolytic actions of tumor necrosis factor-alpha in primary rat adipocytes

Increased systemic free fatty acids (FFA) impair insulin sensitivity. In obese and diabetic subjects, production of tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine, is elevated. TNF-alpha has a variety of effects by inducing inflammation, decreasing glucose utilization, and stimulating adipocyte lipolysis to release FFA to plasma. High doses of nonsteroidal anti-inflammatory drug salicylates have long been recognized to lower blood FFA and glucose in humans, although the mechanisms are not fully understood. In this report, we show that sodium salicylate at therapeutic concentrations directly blocks TNF-alpha-stimulated lipolysis and therefore inhibits FFA release from primary rat adipocytes. To elucidate the cellular basis of this action, we show that salicylate suppresses TNF-alpha-induced extracellular signal-related kinase activation and intracellular cAMP elevation, two early events during the lipolysis response to TNF-alpha. Furthermore, salicylate prevents the down-regulation of cyclic-nucleotide phosphodiesterase 3B, an enzyme responsible for cAMP hydrolysis. Perilipins coat intracellular lipid droplet surface by restricting lipase access to the triacylglycerol substrates. TNF-alpha down-regulates perilipin but promotes its phosphorylation during lipolysis stimulation; these actions are efficiently reversed by salicylate. Salicylate slightly reduces basal but completely inhibits TNF-alpha-liberated lipase activity. In contrast, neither salicylate nor TNF-alpha alters the protein levels of hormone-sensitive lipase and adipose triglyceride lipase. In addition, sodium salicylate restricts basal lipolysis simulated by a high concentration of glucose and significantly diminishes the high glucose-enhanced lipolysis response to TNF-alpha. These results provide novel evidence that salicylate directly blocks TNF-alpha-mediated FFA efflux from adipocytes, hence reducing plasma FFA levels and increasing insulin sensitivity.     

Evaluation of tumor necrosis factor-alpha and granulocyte colony-stimulating factor serum levels in lead-exposed smoker workers

Inorganic lead (Pb) is able to modulate the immune response even at low to moderate exposure levels. It inhibits in vitro and in vivo activities of neutrophil leucocytes and influences their blood count in humans. Neutrophil functions are governed by a number of cytokines. Pb has been shown to affect leukocyte production of some of these cytokines in vitro. The objective of this study is to assess serum tumor necrosis factor-alpha (TNF-alpha) and granulocyte colony-stimulating factor (G-CSF) levels of thirty-three male lead-exposed (E) workers at a lead recycling plant as compared with twenty-eight male non-exposed (NE) workers at a food processing plant, whose current smoking habit was known. Serum TNF-alpha and G-CSF levels were measured by a quantitative sandwich enzyme immunoassay. Blood lead levels (Pb-B) were significantly higher in E (geometric mean (GM) 30.7 microg/dl, GSD 1.7; min-max: 9.1-81.6 microg/dl) workers than controls (GM 3.6 microg/dl, GSD 1.7; min-max: 1.0-11.0 microg/dl). E workers had significantly higher serum TNF-alpha (median: 107.1; min-max: 11.1-623.0 pg/ml) and G-CSF levels (median: 53.0, min-max: 31.1-197.0 pg/ml) than NE workers (TNF-alpha: median: 12.0; min-max: 9.4-18.8 pg/ml; G-CSF: median: 34.3, min-max: 25.1-52.2 pg/ml). In particular, the TNF-alpha level was shown to be significantly influenced by lead exposure and smoking habit, as well as by interaction between these two factors. Both serum TNF-alpha and G-CSF levels were correlated with Pb-B and absolute neutrophil count. This study is the first to detect higher serum levels of G-CSF in E over NE workers. Our data confirm that exposure to low to medium doses of lead may interfere in the complex cytokine network involved in inflammation, especially in workers who are current smokers.