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101.
目的探讨过氧化体增殖物激活型受体α(PPARα)的特异性激活物亚油酸对HepG2细胞1型纤溶酶原激活物抑制剂(PAI-1)mRNA表达及其活性的影响和在该基因转录调控中的作用机制.方法用不同浓度亚油酸为诱导因素刺激HepG2细胞,采用半定量RT-PCR法检测PAI-1mRNA水平,发色底物法检测PAI-1的活性变化.构建四个含PAI-1启动子序列从-804~+17间不同长度片段驱动的荧光素酶报告基因质粒,体外瞬时转染HepG2细胞,检测荧光素酶的活性.结果与对照组相比,亚油酸组能使HepG2细胞PAI-1mRNA表达及蛋白活性显著升高(P<0.05,P<0.01),且呈一定剂量依赖性;亚油酸诱导可使PAI-1转录活性显著升高(P<0.01);与转染质粒PAI-pGL3-A(-804/+17)相比较,当转染质粒含有PAI-pGL3-B(-636/+17)、PAI-pGL3-C(-449/+17)时,荧光素酶活性显著降低(P<0.01);共转染PPARα表达质粒(PPARα-pSG5)的细胞在亚油酸诱导下PAI-1转录活性显著升高(P<0.01).结论亚油酸可以增加HepG2细胞PAI-1mRNA表达及其蛋白活性,调节PAI-1的基因转录,PPARα参与亚油酸对PAI-1基因的表达调控;在PAI-1启动子-804~-636、-449~-276区域内存在亚油酸作用的调控PAI-1基因表达的序列. 相似文献
102.
Summary. Patients with mild or moderate haemophilia A usually have a mild bleeding disorder requiring only occasional treatment with factor VIII (FVIII) concentrates. The frequency of inhibitor development in such patients has been the subject of several recent surveys, which significantly modified our appreciation of this complication. Studies of the anti-FVIII antibodies provided an explanation for the different bleeding phenotypes observed in mild/moderate haemophilia A patients with inhibitors. Antibodies distinguishing between the patient's mutant FVIII and the normal wild-type FVIII were characterized, in addition to antibodies inhibiting completely or only partially FVIII activity. T lymphocytes recognizing FVIII and likely involved in the development of the immune response to FVIII were successfully identified. The FVIII peptides recognized by those FVIII-specific cells bind to many major histocompatibility complex (MHC) class II molecules, which may provide an explanation for the lack of strong association between MHC haplotypes and inhibitor development. Although these studies have advanced our understanding of the conditions leading to inhibitor development, further work is required to determine whether the mode of FVIII administration significantly influences inhibitor development. Further studies of the genetic factors are also required to fully understand the mechanisms leading to inhibitor development in patients with mild/moderate haemophilia A. 相似文献
103.
104.
高脂血症对血浆t-PA和PAI-1活性的影响 总被引:2,自引:0,他引:2
目的 探讨高脂血症患者的纤溶系统的变化。方法 选取正常人及高脂血症者,测定其血脂、血浆t—PA和PAI-1活性。结果 高脂血症组比正常人血浆t—PA活性下降,而PAI-1的活性有升高;在TG及LDL-C升高者,其血浆t—PA活性比正常人血浆t—PA活性降低,而血浆PAI-1活性比正常人升高;单纯TC升高者血浆PAI-1活性接近正常人组,而血浆t—PA活性比正常人组明显降低。结论 高脂血症对纤溶系统有一定的影响,其中甘油三酯和LDL-C对纤溶系统的影响更明显,而胆固醇对纤溶系统也有一定的影响。 相似文献
105.
Alex W Wilson Stephen J Medhurst Claire I Dixon Nick C Bontoft Lisa A Winyard Kim T Brackenborough Jorge De Alba Christopher J Clarke Martin J Gunthorpe Gareth A Hicks Chas Bountra Daniel S McQueen Iain P Chessell 《European Journal of Pain》2006,10(6):537-549
Clinically, inflammatory pain is far more persistent than that typically modelled pre-clinically, with the majority of animal models focussing on short-term effects of the inflammatory pain response. The large attrition rate of compounds in the clinic which show pre-clinical efficacy suggests the need for novel models of, or approaches to, chronic inflammatory pain if novel mechanisms are to make it to the market. A model in which a more chronic inflammatory hypersensitivity phenotype is profiled may allow for a more clinically predictive tool. The aims of these studies were to characterise and validate a chronic model of inflammatory pain. We have shown that injection of a large volume of adjuvant to the intra-articular space of the rat knee results in a prolonged inflammatory pain response, compared to the response in an acute adjuvant model. Additionally, this model also results in a hypersensitive state in the presence and absence of inflammation. A range of clinically effective analgesics demonstrate activity in this chronic model, including morphine (3mg/kg, t.i.d.), dexamethasone (1mg/kg, b.i.d.), ibuprofen (30mg/kg, t.i.d.), etoricoxib (5mg/kg, b.i.d.) and rofecoxib (0.3-10mg/kg, b.i.d.). A further aim was to exemplify the utility of this chronic model over the more acute intra-plantar adjuvant model using two novel therapeutic approaches; NR2B selective NMDA receptor antagonism and iNOS inhibition. Our data shows that different effects were observed with these therapies when comparing the acute model with the model of chronic inflammatory joint pain. These data suggest that the chronic model may be more relevant to identifying mechanisms for the treatment of chronic inflammatory pain states in the clinic. 相似文献
106.
TNP-470对裸鼠体内人结肠癌细胞增殖和凋亡的影响 总被引:1,自引:0,他引:1
目的 研究TNP-470对裸鼠体内人结肠癌细胞增殖和凋亡的影响。方法 将16只人结肠癌皮下移植瘤裸鼠随机分成实验组和对照组,实验组隔日予以TNP-47030mg/kg,皮下注射,对照组予以相同体积的生理盐水,4周后处死,应用免疫组织化学法(免疫组化)和图象分析技术检测肿瘤细胞中增殖细胞核抗原(PCNA)的表达,TdT介导的dUTP缺口末端标记(TUNEL)法检测肿瘤细胞的凋亡,透射电镜观察凋亡细胞的超微结构。结果 TNP-470明显抑制了肿瘤的生长,抑瘤率为45.53%。实验组肿瘤中PCNA的表达显低于对照组,凋亡指数上升,电镜下可见典型的细胞凋亡形态学变化。结论 TNP-470除了通过抗血管生成作用抑制肿瘤生长外,还可通过抑制LOVO细胞本身的增殖和诱导凋亡发挥抗肿瘤作用。 相似文献
107.
2005~2007年我国非甾体抗炎药市场应用分析 总被引:1,自引:0,他引:1
目的:以骨骼肌肉系统使用非甾体抗炎药物为例,分析该类药物在2005~2007年的销售数量、销售金额及生产厂家风云榜。方法:采用药物分类累加的方法统计2005~2007年非甾体抗炎药的销售数量和金额排序,并对前10位药品销售数量和金额对比,及前10位厂家对比。结果:双氯芬酸稳居销售榜首,美洛昔康、布洛芬等药物位居其后。结论:新一代的非甾体抗炎药已经占据主要市场,各类药物各有特色,但是仍需注意其消化系统及心血管系统的不良反应。 相似文献
108.
109.
A methoxylated fatty acid that inhibits phospholipase A(2) (PLA(2); EC 3.1.1.4) was purified from the brown seaweed Ishige okamurae. Approximately 8.1 mg of the inhibitory compound, 7-methoxy-9-methylhexadeca-4,8-dienoic acid, was isolated from 1 kg of I. okamurae powder. Recombinant PLA(2) derived from the pathogenic bacterium Vibrio mimicus was used as the target enzyme. The methoxylated fatty acid compound competitively inhibited PLA(2) with a Ki value of 3.9 microg/mL. The concentrations required for 50% inhibition of PLA(2), oedema and erythema were 1.0 microg/mL, 3.6 mg/mL and 4.6 mg/mL, respectively. The compound strongly inhibited PLA(2) activity in vitro and had potent antiinflammatory activity in vivo. 相似文献
110.
派立明与贝特舒联合应用对降眼压的临床观察 总被引:1,自引:0,他引:1
目的评价1.00%派立明(AZOPT)与0.25%贝特舒点眼液每日两次点眼对原发性开角型青光眼、高眼压症及抗青光眼术后高眼压的降眼压效果及安全性。方法31例患者51只眼纳入为期2个月的前瞻性研究。在停用其他抗青光眼药物足够长的时间后测量基础值,用药后每2周复查一次共4次,同时观察眼局部及全身副作用。结果用药前眼压为23.85±1.80 mmHg,4次随访眼压下降均值6.55 mmHg(6.06~7.04),眼压下降率27.50%(26.62~28.59%)。少数病例出现烧灼感、视物模糊、口苦等症状,均为轻度能耐受,对视力、眼底无影响。结论派立明与贝特舒联合用药具有稳定的降眼压效果,具良好耐受性。 相似文献