巨噬细胞对低密度脂蛋白的修饰和PGE2抗AS作用的实验研究

目的：研究巨噬细胞对低密度脂蛋白（LDL）的修饰和前列腺素E2（PGE2）对动脉粥样硬化形成的抑制作用。方法：以巨噬细胞（Mp）作用LDL,并没PGE2（20mg/L组）,检测每组过氧化脂质含量,谷胱甘肽过氧化物酶活性,及形态计量学测定细胞变化和含脂量。结果：细胞修饰组的脂质过氧化物含量高于给PGE2组,而谷胱甘肽过氧化物酶活性显著低于给药组。作用24小时的修饰组细胞面积明显增大,摄取增加,均分别显著高于给药组和细胞对照组。结论：提示Mp能够氧化修饰LDL并能摄取脂质,导致泡沫细胞形成。大剂量PGE2有抗LDL氧化修饰,抑制Mp细胞摄脂,和泡沫细胞形成,从而抑制动脉样硬化发生的作用。     

血凝素样氧化低密度脂蛋白对单核巨噬细胞源泡沫细胞基质金属蛋白酶-9的调控作用

目的观察氧化低密度脂蛋白(ox-LDL)对人单核巨噬细胞源泡沫细胞分泌的基质金属蛋白酶-9(MMP-9)的表达和活性的影响,以及此过程中血凝素样氧化低密度脂蛋白受体-1(LOX-1)的调控作用。方法体外原代培养人单核细胞来源的巨噬细胞,传至2～6代用于实验。依不同浓度ox-LDL(20、40、80mg/L)作用24h,以及ox-LDL40mg/L作用1、12、24h分组,另设LOX-1受体阻断剂多聚肌苷酸(PolyI)干预组。反转录-聚合酶链反应(RT-PCR)测定LOX-1和MMP-9mRNA表达,酶谱法分析MMP-9的活性。结果 ox-LDL作用后,LOX-1和MMP-9mRNA表达升高,MMP-9的分泌及活性升高(P<0.05),且诱导作用呈浓度-时间依赖性;多聚肌苷酸抑制后,MMP-9mRNA表达及活性明显下降(P<0.05)。结论 LOX-1作为ox-LDL的特异性受体,介导ox-LDL诱导的上调单核巨噬细胞LOX-1、MMP-9表达及活性的作用。     

松果体和褪黑激素通过下丘脑影响大鼠腹腔巨噬细胞化学发光(英文)

目的:研究松果体和褪黑激素(Mel)是否通过下丘脑影响腹腔巨噬细胞功能.方法:松果体切除术;腹腔巨噬细胞化学发光测定;下丘脑地诺前列酮放射免疫测定;下丘脑注射Mel.结果:松果体切除后腹腔巨噬细胞化学发光值降低,下丘脑地诺前列酮含量升高,16:00 ip Mel(10 μg kg~(-1)d~(-1)×7d)可使其恢复,并升高正常大鼠腹腔巨噬细胞化学发光值,降低其下丘脑地诺前列酮含量.腹腔巨噬细胞化学发光值与下丘脑地诺前列酮含量的变化存在负相关(相关系数,r=-0.78,P<0.01).于下丘脑注射Mel 2μg,能提高正常大鼠和松果体切除大鼠腹腔巨噬细胞化学发光值.结论:下丘脑是松果体Mel影响腹腔巨噬细胞功能的主要作用部位之一.     

氧化低密度脂蛋白诱导体外培养的巨噬细胞CRP的表达

目的:证实作为动脉粥样硬化病变中重要的炎细胞成分之一的巨噬细胞可表达CRP,并受氧化低密度脂蛋白(OX-LDL)的调节。方法:以不同浓度的OX-LDL处理外周血单核细胞(PBMC)来源的巨噬细胞和THP-1巨噬细胞,应用酶联免疫吸附实验(ELISA)测定浓缩的上清液中CRP的含量,并应用反转录聚合酶链反应(RT-PCR)测定CRP在mRNA水平上的变化。结果:来源于PBMC的巨噬细胞可表达CRP,其浓度相对较低,为(0.45±0.37)μg/L,OX-LDL以浓度依赖性方式显著增加CRP的生成,100mg/LOX-LDL组CRP增至(8.12±0.43)μg/L,但后加入的LPS可降低相应浓度的OX-LDL所诱导的CRP的表达,50mg/LOX-LDL 1μg/LLPS组与50mg/LOX-LDL组比较,CRP的表达有显著性差异(P<0.01)。以THP-1巨噬细胞为材料的RT-PCR也进一步证实以上结果。结论:巨噬细胞可产生CRP并受OX-LDL的调节,局部生成的CRP直接参与动脉粥样硬化的形成。     

辛伐他汀对氧化型低密度脂蛋白及葡萄糖诱导的LOX-1表达的不同作用

【摘要】目的研究辛伐他汀干预对于氧化型低密度脂蛋白（ox-LDL）及葡萄糖诱导的巨噬细胞表面血清凝集素样氧化型低密度脂蛋白受体（LOX）-1表达的影响,以及核因子（NF）-κB的作用。方法U937细胞经佛波酯诱导分化后,将含有50mg/L ox-LDL和（或）25mmol/L葡萄糖的培养液与上述细胞共同孵育,应用吡咯烷二硫氨基甲酸（PDTC）及不同浓度辛伐他汀（1、10μmol/L）干预上述细胞,干预前后用ELISA检测LOX-1蛋白的表达及NF-κB的活性,RT-PCR检测LOX-1mRNA含量。结果ox-LDL、高糖及联合组均上调LOX-1表达,NF-κB的抑制剂PDTC可以抑制其作用,辛伐他汀可以下调ox-LDL诱导的LOX-1表达增加,且高浓度下调明显;但辛伐他汀对于高糖诱导LOX-1表达无明显影响。各组间NF-κB活性改变与LOX-1表达基本一致。结论辛伐他汀可以下调ox-LDL诱导的巨噬细胞LOX-1表达,但对葡萄糖诱导的LOX-1表达无明显影响,LOX-1表达调控与NF-κB信号途径有关。     

巨噬细胞泡沫化抑制剂的研究进展

胆固醇酯蓄积的巨噬细胞(泡沫细胞)是早期动脉粥样硬化斑块的主要组成和特征。它通过其细胞表面的多种受体无限制地摄取氧化型低密度脂蛋白(ox-LDL)颗粒及其他配体,结果在巨噬细胞内有大量的胆固醇酯和三酰甘油蓄积,使巨噬细胞发展成为泡沫细胞。因此,通过各种途径抑制这种在巨噬细胞的过量脂质蓄积,可以起到预防和治疗动脉粥样硬化的作用。     

前列腺素E1和E2对体外内皮细胞修饰低密度脂蛋白的作用

低密度脂蛋白(LDL)的氧化修饰是动脉粥样硬化形成(AS)的重要机制之一。细胞对LDL的修饰作用是近年来研究的热点。我们利用体外培养的免主动脉内皮细胞与LDL共同孵育,以探讨内皮细胞对LDL的氧化作用。有研究表明,大剂量前列腺素EZ(PGE2)(2～20mg/L)抑制AS,小剂量则促进AS[1];亦见有PGE1抗AS作用的报道。因此,本研究拟从抗LDL氧化修饰的角度探讨二者的抗AS机理。 材料与方法 1.家兔主动脉内皮细胞的培养　健康幼龄雌性白色家兔,体重 1.2kg,气栓处死。迅速于无菌条件下取出主动脉,洗净血迹,去除外膜及结缔组织。纵行剪开管壁,将…     

肝硬化和十二指肠溃疡患者血浆生长抑素及前列腺素E2的变化和比较

目的观察十二指肠溃疡及肝硬化患者胃肠粘膜保护性激素--血浆生长抑素(SS)和前列腺素E2(RGE2)含量的变化。方法用放免法检测正常人20例，十二指肠溃疡(Du)和肝硬化患者各20例血浆SS和PGF2含量。结果血浆SS正常人为(39.5±9.3)μg/L,Du组为(24.1±4.4)μg/L，肝硬化患者为(20.3±7.6)μg/L。血浆PGE2正常人为(2617±344)μg/L,Du组为(2102±507)μg/L，肝硬化患者为(1308±273)μg/L，Du及肝硬化病人血浆SS和PGE2含量比正常人降低(均P＜0.01)。结论Du和肝硬化患者血浆SS和PGE2含量均减少，后者比前者减少更显著，这可能是Du和肝硬化门脉高压性胃肠病发病的重要因素之一。     

大孔吸附树脂对低密度脂蛋白吸附性能的研究

目的研究大孔吸附树脂对低密度脂蛋白(LDL)的吸附性能.方法在体外实验中比较了3种吸附树脂对LDL的吸附效率,筛选出对LDL吸附效率高、对高密度脂蛋白(HDL)吸附效率低的2号树脂,并观察了2号大孔树脂对高脂血症实验动物模型的LDL和HDL吸附效率及其血液相容性. 结果2号大孔树脂对高脂血症模型动物LDL的吸附率达57.9%,对HDL的吸附率为11.5%,且对血液相容性良好. 结论2号大孔树脂是一种具有应用前景的新的医用材料.     

血清胆红素和氧化修饰低密度脂蛋白水平与冠心病患者冠状动脉病变程度关系研究

目的探讨血清胆红素（BIL）与氧化修饰低密度脂蛋白（OX-LDL）水平和冠状动脉粥样硬化性心脏病（CHD）患者冠状动脉病变间的关系及其临床意义。方法160例患者按冠状动脉造影结果分为CHD组和非CHD组,采用Gensini法计算冠状动脉病变积分（CSS）。检测空腹血清总胆红素（TBIL）、直接胆红素（DBIL）、间接胆红素（IBIL）、总胆固醇（TC）、三酰甘油（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）浓度,氧化修饰低密度脂蛋白（OX-LDL）水平。结果CHD组血清TBL明显低于非CHD组[（7.9±2.7）μmol/Lvs（15.5±3.9）μmol/L,P〈0.01],而血浆OX-LDL明显高于非CHD组[（98±38）mmol/Lvs（29±11）μmol/L,P〈0.01]。相关分析显示血清TBIL与血浆OX-LDL的变化呈负相关（r=-0.65,P〈0.01）。双变量分析显示TBIL、DBIL、IBIL与CSS呈负相关（P〈0.05或〈0.01）结论血清胆红素代谢紊乱参与了CHD的发生和发展,其水平变化与冠状动脉病变的严重性有关。CHD患者血清TBIL抗LDL氧化能力的减弱可能是导致OX-LDL升高的重要原因。     

前列腺素E2栓剂用于过期妊娠引产的临床研究

目的 探讨前列腺素E2栓剂用于过期妊娠引产的疗效.方法 将孕41周～41+6周、单胎、头位、未破膜的初产妇80例,随机分为研究组和对照组各40例,研究组阴道后穹窿放置前列腺素E2栓剂1枚,对照组微量泵应用催产素.观察并记录用药后6 h宫颈评分改善情况、用药至临产所需时间、用药至分娩所需时间、24 h引产成功率、胎儿、羊水情况.结果 两组宫颈评分改善情况、引产成功率、临产和分娩所需时间比较差异均有统计学意义(P<0.05);而胎心异常和羊水粪染等方面无统计学差异(P>0.05).结论 普贝生相对于催产素用于延期妊娠引产更省时、成功率更高,且不增加分娩风险.     

Prostaglandin E1 inhibits acute cell dehydration thirst

Intraperitoneally injected PGE₁ (100 μg/Kg) inhibits specifically the drinking induced by both IP and IV 2 M NaCl (6 ml/Kg) and compound 48/80 (100 μg/Kg, IP). Probenecid (150 mg/Kg, IP), which is not a dipsogen, has no effect on the PGE₁ induced inhibition of acute cell dehydration thirst. It is concluded the PGE₁ acts upon the peripheral mast cells, inhibiting their secretion and thus affecting the water intake associated with the activation of these cells either by hypertonicity or specific stimulants of amine release. These results raise the possibility that endogenous prostaglandins might be involved in the modulation of some of the signals which convey to the brain information on the tonicity of the body fluids.     

Prostaglandin E1 fever in the crayfish Cambarus bartoni

Groups of 10 crayfish were injected with prostaglandin E₁, at 1 of 3 pharmacological doses (0.5, 0.1 or 0.05 mg), into the haemocoel, and individually allowed to thermoregulate in electronic shuttleboxes for 24 hr. The mean preferred temperature of each group was then compared with their mean preferred temperature for 24 hr prior to injection, and with the mean preferred temperature of 10 crayfish injected with pyrogen-free saline. Dosage-dependent increases in preferred temperature were observed in the crayfish injected with PGE₁, ranging from 1°C at the lowest dosage to 3.4°C at the highest dosage, above the normal thermal preferendum for this species of 22.1°C.     

Dissolution behavior of 17β-estradiol (E2) from povidone coprecipitates. comparison with microcrystalline and macrocrystalline E2

The dissolution rates of macrocrystalline 17β-estradiol (E₂), microcrystalline E₂and E₂-povidone coprecipitates and physical mixtures varying in weight ratio from 1 : 1 to 1:49 were determined at 37°C. E₂ dissolution from the coprecipitates was markedly faster than that from either macro- or microcrystalline forms of the drug and was found to increase with decreasing E₂-to-povidone weight ratio. Based on the results of X-ray diffraction, differential scanning calorimetric. Raman spectroicopic, and thermal gravi metric analysis studies, it is concluded that the formation of a more water soluble, high energy state of E₂ is responsible for the increased dissolution rate of this natural cstrogen from low weight ratio povidone coprecipitates. These findings suggest that the use of E₂-povidone coprecipitates may increase the systemic availability of E₂.     

微粒体前列腺素E2合成酶-1抑制剂研究进展

传统的解热镇痛抗炎药主要以环氧合酶-2(COX-2)为靶点,在世界范围内拥有巨大的市场,虽几经改良,但仍存在较多副作用,一直没有良好的替代品。自1999年发现微粒体前列腺素E2合成酶-1(mPGES-1)以来,部分目光敏锐的研究人员注意到这可能是解热镇痛抗炎药的一个新靶点。此后近10年时间内,人们就其生物化学、病理生理学特性进行了大量研究。然而,其药学方面的研究尚处于起始阶段,但国际制药公司已将其作为开发提高解热镇痛抗炎药的重要靶标。主要就mPGES-1抑制剂的研究进展作一简述。     

Effect of prostaglandin E2 on acetylcholine release from some peripheral cholinergic nerve terminals

The effect of prostaglandin E₂ (PGE₂) on the acetylcholine (ACh) release evoked from rat phrenic nerve terminals and from Auerbach's plexus of the guinea-pig ileum was investigated. PGE₂ enhanced the evoked release of ACh from phrenic nerve terminals and from Aurbach's plexus in a concentration-dependent manner. Preincubation with 7-oxa-13-prostynoic acid, the PGE receptor blocker, and indomethacin inhibited the PGE₂-induced increase of evoked release of ACh while atropine failed to do so. Whereas a single administration of either 7-oxa-13-prostynoic acid or indomethacin significantly inhibited the control evoked release of ACh from the Auerbach's plexus, they failed to alter the control evoked release of ACh from the phrenic nerve terminals. The study indicates that the PGE₂-induced increase in release of ACh from cholinergic nerve terminals is accomplished through activation of prostaglandin receptors and that PGE₂ may play a physiological role in ACh liberation from the cholinergic autonomic nerve terminals but not from motor nerve terminals.     

Effects of indomethacin and prostaglandins I2 and E2 on the tone of human isolated mesenteric arteries

The actions of indomethacin (IND), PGE₂ and PGI₂ were studied on the tone of isolated mesenteric arteries obtained from operated patients. The cyclooxygenase inhibitors IND (3 μ mol/l) and suprofen (0.58 μ mol/l) increased the resting tone and potentiated the contractile responses to electrical stimulation and noradrenaline. Low concentrations of PGE₂ (0.7?5.6 × 10^?9 mol/l) decreased the baseline tone and reduced the stimulation-evoked contractions whereas higher concentrations (from 5.7 × 10^?8 mol/l) increased the tone of the vessels. PGI₂ (0.7–10.8 × 10^?9 mol/l) also relaxed IND-treated arteries but, in contrast to PGE₂, it did not produce contraction even at a concentration of 10^?6 mol/l. Prostacyclin reduced the tone evoked and sustained by a high concentration of PGE₂ or PGE_2α, the IC₅₀ values being 46.2 or 7.9 × 10^?9 mol/l, respectively. The contractile responses to electrical stimulation and to noradrenaline were also inhibited by PGI₂ (IC₅₀ 5.6 and 6.8 × 10^?9 mol/l, respectively). These results suggest that the smooth muscle cells of human mesenteric arteries are just as sensetive to IND, PGE₂ and PGI₂ as are those from laboratory animals. Our observations may be of clinical importance.     

冠心病患者口服刺梨汁抗低密度脂蛋白氧化作用的研究

目的：为寻找有效抗脂蛋白氧化剂。方法：28例男性心肌梗塞存活者持续口服富含多种抗氧化剂的天然刺梨果汁30天，每天三次，每次10ml。结果：服刺梨汁后患者肝肾功能、血糖、血脂及载脂蛋白水平均无变化，而血浆甘油三酯水平下降；血浆纸生素C、E水平显著升高；氧化低密度脂蛋白（LDL）水平及LDL氧化程度显著降低；LDL氧化延滞时间亦明显延长。结论：刺梨汁提高了患者血浆抗氧化剂水平及LDL抗氧化能力，导致氧化LDL水平降低。     

Central effects of prostaglandins E2, A1 and F2α in adult fowls

Adult fowls (Gallus domesticus) with cannulae chronically implanted into the 3rd cerebral ventricle, the anterior or posterior hypothalamus and various other sites of the brain received infusions of prostaglandins (PG) E₂, A₁ or F_2α. The effects of these drugs on behaviour, posture, electrocortical activity and body temperature were studied.Prostaglandin E₂ and PGA₁ infused into the 3rd cerebral ventricle and into the hypothalamus induced sedation and/or sleep and increased body temperature. Prostaglandin F_2α lowered body temperature but did not affect behaviour.Behavioural, electrocortical and body temperature changes were dose-dependent. Prostaglandin E₂ was more potent than FGA₁Infusion of PGE₂, PGA₁ and PGF_2α into other cerebral areas e.g. paleostriatum augmentatum, telencephalon and mesencephalon lacked effects on behaviour, electrocortical activity and body temperature.The site through which behavioural, electrocortical and body temperature effects of prostaglandins E₂ and A₁ were mediated appears to be the hypothalamus.