TG,VLCL和OX—VLDL对L—02和HLF细胞增殖及合成细胞外基质的影响

目的 探讨脂质对肝细胞和成纤维细胞生物学活性的影响。方法 以ＭＴＴ法、透明质酸（ＨＡ）放免测定法及＾３Ｈ－脯氨酸掺入法，观察４种不同浓度的甘油三酯（ＴＧ）、极低密度脂蛋白（ＶＬＤＬ）和化极低密度脂蛋白（ＯＸ－ＶＬＤＬ）对无血清培养正常人成人肝细胞（Ｌ－０２细胞）和人胚肺成纤维细胞（ＨＬＦ细胞）增殖及合成ＨＡ和胶原蛋白的影响，结果 一定浓度的ＴＧ、ＶＬＤＬ和ＯＸ－ＶＬＤＬ可影响ＨＬＦ和Ｌ－０２细胞的     

不饱和脂肪酸对L-02和HLF细胞增殖及合成细胞外基质的影响

目的探讨不饱和脂肪酸对肝细胞和成纤维细胞增殖及合成细胞外基质的影响．方法以ＭＴＴ法、透明质酸（ＨＡ）ＲＩＡ法及３Ｈ脯氨酸掺入法，观察４种不同浓度的油酸、亚油酸和花生四烯酸对无血清培养正常成人肝细胞（Ｌ０２）、人胚肺成纤维细胞（ＨＬＦ）增殖及合成细胞外基质（ＥＣＭ）的影响．结果油酸、亚油酸可影响ＨＬＦ细胞和（或）Ｌ０２细胞增殖，并促进其合成胶原和ＨＡ，而花生四烯酸对其增殖及合成ＥＣＭ的影响不明显．结论肝内游离的不饱和脂肪酸增多可促进肝纤维化的发生和发展．     

氧化低密度和极低密度脂蛋白对单核细胞血小板源性生长因子B链表达的影响

在单核细胞的培养基中分别加入２５ｍｇ·Ｌ￣（－１）低密度脂蛋白（ｌｏｗｄｅｎｓｉｔｙｌｉｐｏｐｒｏｔｅｉｎ，ＬＤＬ）、氧化ＬＤＬ（ｏｘｉｄｉｚｅｄＬＤＬ，ＯＬＤＬ）、极低密度脂蛋白（ｖｅｒｙｌｏｗｄｅｎｓｉｙｌｉｐｏｐｒｏｔｅｉｎ，ＶＬＤＬ）和氧化极低密度脂蛋白（ｏｘｉｄｉｚｅｄＶＬＤＬ，ＯＶＬＤＬ），培养２４ｈ后再用无血浆脂蛋白培养基收集条件培养基，并观察此条件培养基对￣３Ｈ－ＴｄＲ投入血管壁平滑肌细胞ＤＮＡ的影响。用抗血小板源性生长因子Ｂ链抗体（抗ＰＤＧＦ－Ｂ抗体）作疫组织化学染色。结果表明，单核细胞能表达ＰＤＧＦＢ，ＯＬＤＬ和ＯＶＬＤＬ能明显地促进单核细胞ＰＤＧＦ－Ｂ的表达，其条件培养基亦能促进￣３Ｈ－ＴｄＲ掺入平滑肌细胞ＤＮＡ内。上述结果提示，ＯＬＤＬ和ＯＶＬＤＬ通过加强单核细胞分泌ＰＤＧＦ－Ｂ并促进平滑肌细胞增殖而在动脉粥样硬化的发病过程中起作用。     

合成多肽体外诱导乙肝病毒抗原特异性T杀伤细胞实验研究

目的及方法 为探讨ＨＢＶ抗原特异性细胞毒Ｔ细胞（ＨＢＶ－ＣＴＬ），根据ＨＢｃＡｇ的ＨＬＡ分子结合关键序列合成抗原多肽２段，分别与转铁蛋白（Ｔｆ），抗ＣＤ单克隆抗体（ＣＤ３ｍＡｂ）和ＩＬ－２联合体外诱导ＨＢＶ－ＣＴＬ，应用＾３Ｈ－ＴｄＲ释放法分别测定ＨＢＶ－ＣＴＬ对ＨＢＶＤＮＡ转染的ＨｅｐＧ２．２．１５细胞特异性活性及无ＨＢＶＤＮＡ转染的ＨｅＰＧ２细胞的非特异性杀伤率。结果 ＨＢＶ－ＣＴＬ对ＨＢＶＤ     

HLA部分不相合异基因外周血干细胞移植造血重建

目的：了解ＨＬＡ部分不相合异基因外周血干细胞移植（ＡＬＬｏ－ＰＢＳＣＴ）后造血功能重建情况,及在发生严重移植物抗宿主病（ＧＶＨＤ）时对造血功能的影响。方法：对患者移植后的血象、骨髓象,生化指标进行动态观察并分析结果。结果：移植后,＋ １３ ｄ 白细胞达２．２×１０９／Ｌ;＋ ２０ ｄ 骨髓增生活跃;＋ ４６ ｄ ＡＢＯ 血型、ＭＮ 血型、ＨＬＡ表型、ＨＬＡ ＤＮＡ分型均转为供型者,显示移植物植入成功。＋ １０ ｄ 开始出现ＧＶＨＤ征象,＋ ２９ ｄ 达ＧＶＨＤⅢ度,经用马抗人胸腺细胞球蛋白（ＡＴＧ）、ＣＤ３ 单抗、ＣＤ２５单抗后,症状消失。同时造血功能明显受抑。结论：①ＡＬＬｏ－ＰＢＳＣＴ造血重建过程中,应用Ｇ－ＣＳＦ可促使移植干细胞加快分化、增殖。②发生严重ＧＶＨＤ后,用ＡＴＧ等药物抑制Ｔ细胞,同时减少Ｔ细胞分泌ＧＭ－ＣＳＦ等相关细胞因子,致造血功能受抑制。     

小儿病毒性心肌炎的氧自由基变化及其相关因素

对６１例病毒性心肌炎（ＶＭＣ）患儿检测了ＳＯＤ、ＧＳＨ－ＰＸ、ＭＤＡ。发现ＶＭＣ患儿发病１周内ＳＯＤ、ＧＳＨ－ＰＸ下降,ＭＤＡ升高;经大剂量维生素Ｃ治疗后,ＳＯＤ、ＧＳＨ－ＰＸ、ＭＤＡ于４～６周恢复正常。ＳＯＤ、ＧＳＨ－ＰＸ与ＣＫ－ＭＢ呈负相关;与ＥＦ、ＦＳ呈正相关;ＭＤＡ与ＣＫ－ＭＢ呈正相关,与ＧＳＨ－ＰＸ、ＳＯＤ呈负相关。ＭＤＡ升高与否和心电图ＳＴ－Ｔ改变有关,ＧＳＨ－ＰＸ、ＳＯＤ降低与否和心     

甘油三酯和极低密度脂蛋白对肝星状细胞增殖的影响

目的探讨甘油三酯（ｔｒｉｇｌｙｃｅｒｉｄｅ，ＴＧ）和极低密度脂蛋白（ｖｅｒｙｌｏｗ－ｄｅｎｓｉｔｙｌｉｐｏｐｒｏｔｉｏｎ，ＶＬＤＬ）对大鼠肝星状细胞（ｈｅｐａｔｉｃｓｔｅｌａｔｅｃｅｌ，ＨＳＣ）增殖的影响。方法用链霉蛋白酶和胶原酶原位灌流，Ｎｙｃｏｄｅｎｚ密度梯度离心分离大鼠ＨＳＣ，并以ＭＴＴ比色法观察ＴＧ和ＶＬＤＬ对ＨＳＣ增殖效应。结果ＴＧ和ＶＬＤＬ可影响ＨＳＣ的增殖，ＴＧ和ＶＬＤＬ浓度分别在１２５ｍｇ／Ｌ和（２５～１００）ｍｇ／Ｌ时对ＨＳＣ增殖有促进作用（Ｐ＜００５或Ｐ＜００１）。结论体外细胞培养表明，ＴＧ和ＶＬＤＬ可促进ＨＳＣ增殖，其与脂肪肝肝纤维化的发生可能有关。     

肝损伤小鼠肝组织氧化／抗氧化平衡的变化及其与TXA2／PGI2？…

目的：探讨氧自由基（ＯＦＲ）及ＴＸＡ２－ＰＧＩ２在实验性肝损伤中的作用。方法：检测肝损伤小鼠肝组织过氧化脂质（ＬＰＯ）、超氧化物歧化酶（ＳＯＤ）含量以及血浆ＴＸＡ和ＰＧＩ２浓度。结果：与对照组比较肝损伤小鼠ＬＰＯ明显升高、ＳＯＤ明显降低，当归可逆转ＬＰＯ和ＳＯＤ的变化；肝损伤小鼠血浆ＴＸＢ２高于对照组，其浓度与肝细胞ＬＰＯ含量呈正相关（ｒ＝０．９５，Ｐ〈０．０１）。结论：ＯＦＲ与ＴＸＡ２／ＰＧＩ２     

间质性肺疾病支气管肺泡灌洗液的酶活性研究

目的探讨支气管肺泡灌洗液（ＢＡＬＦ）多项酶活性与间质性肺疾病（ＩＬＤ）的关系。方法检测３０例ＩＬＤｓ：包括特发性肺纤维化（ＩＰＦ）１８例和结节病（Ｓａｒｃ）１２例与９例正常对照者的ＢＡＬＦ中超氧化歧化酶（ＳＯＤ）、谷胱甘肽过氧化物酶（ＧＳＨ－ＰＸ）、血管紧张素转换酶（ＡＣＥ）和乳酸脱氢酶（ＬＤＨ）活性，并分类计数ＢＡＬＦ细胞成份。结果（１）ＩＰＦ组ＢＡＬＦ中各项酶活性均与对照组间差异有显著性（ＳＯＤ和ＧＳＨ－ＰＸ降低，ＡＣＥ和ＬＤＨ升高）（Ｐ＜０．０５）；而Ｓａｒｃ组仅见ＡＣＥ明显增高（Ｐ＜０．０５）。（２）ＢＡＬＦ－ＡＣＥ与Ｓａｒｃ组淋巴细胞百分比及ＣＤ＋４／ＣＤ＋８比值均有显著线性相关（Ｐ＜０．０５）。结论ＢＡＬＦ中ＳＯＤ、ＧＳＨ－ＰＸ、ＡＣＥ和ＬＤＨ活性测定，有助于进一步探讨ＩＬＤ发病机理和提供辅助诊断依据，ＢＡＬＦ－ＡＣＥ对判断Ｓａｒｃ活动性有重要临床意义。     

90例85岁以上老人血脂,脂蛋白和载脂蛋白的研究

对９０例８５岁以上高龄老人的血脂、脂蛋白和载脂蛋白进行测定，并与陈旧性心肌梗塞（ＯＭＩ）组对比。结果显示：与ＯＭＩ组比较，高龄老人血清ＴＣ、ＬＤＬ－Ｃ、ＡｐｏＡⅠ和ＡｐｏＢ_（１００）的明显低，而ＨＤＬ－Ｃ／ＴＣ、ＨＤＬ－Ｃ／ＬＤＬ－Ｃ和ＡｐｏＡⅠ／ＡｐｏＢ_（１００）明显高；ＴＧ、ＨＤＬ－Ｃ和ＶＬＤＬ－Ｃ在两组之间无统计学差异。单因素相关分析显示，ＨＤＬ－Ｃ／ＴＣ，ＨＤＬ－Ｃ／ＬＤＬ－Ｃ和ＡｐｏＡⅠ／ＡｐｏＢ_（１００）与长寿呈正相关，与ＯＭＩ呈负相关；而ＴＣ、ＬＤＬ－Ｃ、ＡｐｏＡⅠ和ＡｐｏＢ_（１００）则与长寿呈负相关，与ＯＭＩ呈正相关；ＨＤＬ－Ｃ、ＴＧ和ＶＬＤＬ－Ｃ与长寿和ＯＭＩ几乎无相关关系。对各检测指标进行多元逐步回归分析，ＡｐｏＢ_（１００）对长寿作用最大，其次为ＡｐｏＡⅠ／ＡｐｏＢ_（１００）和ＨＤＬ－Ｃ．因此认为血清ＡＰｏＢ_（１００）水平的低值、ＨＤＬ－Ｃ和ＡｐｏＡⅠ／ＡｐｏＢ_（１００）的高值，是高龄老人血脂、脂蛋白和载脂蛋白的特点，亦是长寿的指标。     

TG、VLDL、0X-VLDL对L-02和HLF细胞增殖及合成细胞外基质的影响

以MTT法、透明质酸(HA)放免测定法及~3H-脯氮酸掺人法,观察4种不同浓度的甘油三酯(TG)、极低密度脂蛋白(VLDL)、氧化极低密度脂蛋白(OX-VLDL)对无血清培养正常成人肝细胞(L-02细胞)、人胚肺成纤维细胞(HLF细胞)增殖及合成细胞外基质(ECM)的影响。结果发现.TG、VLDL、OX.VLDL可影响HLF细胞和/或L.02细胞的增殖,促进其胶原蛋白和HA的合成,其中以OX-VLDL的作用最为明显。提示肝内脂质(特别是OX-VLDL)过多可通过加强脂质过氧化反应促进肝纤维化的发生和发展。     

Plasma lipoproteins and regulation of hepatic metabolism of fatty acids in altered thyroid states

This article reviews our understanding of effects of thyroid hormone excess and deficiency on hepatic metabolism of FFA, and consequent effects on production, secretion, and metabolism of plasma lipoproteins. In the hyperthyroid state the following alterations are observed. Fatty acid oxidation and ketogenesis are stimulated simultaneously with a paradoxical stimulation of fatty acid synthesis, which may be linked by virtue of a blunted response of mitochondrial carnitine palmitoyltransferase I (CPT-I) to malonyl coenzyme A (CoA). Esterification of fatty acid to triglyceride (TG) is reduced, as is the secretion of the very low density lipoprotein (VLDL) (including VLDL TG, cholesterol, and apoprotein); this may be due, in part, to decreased concentrations of glycerol-3-phosphate (G3P) in the hepatic cell. In the intact animal or patient, however, serum TG concentration is variable, which may reflect increased adipose tissue lipolysis and elevated concentrations of plasma FFA, which would tend to drive VLDL secretion by the liver. Clearance of the VLDL and its metabolic product, the low density lipoprotein (LDL), is increased, resulting in decreased plasma total and LDL cholesterol. Although high density lipoprotein (HDL) cholesterol may also be reduced, the ratio of LDL/HDL cholesterol is further decreased. The regulatory role of the lipoprotein apoproteins is less clear, but hepatic apolipoprotein (apo) B secretion (required for VLDL) is diminished, while apo-AI secretion (required for HDL) is stimulated, perhaps both reflecting rates of synthesis. Plasma concentrations of apo-AI are variable, dependent on relative rates of secretion and clearance. In the hypothyroid, many of these effects are reversed, which results in hyperlipoproteinemias and greater risk for the development of atherosclerotic cardiovascular disease.     

Dose-response study of bezafibrate on serum lipoprotein concentrations in hyperlipoproteinanemia.

The effect of bezafibrate in the dosages 450, 900 and 1350 mg daily on serum lipoprotein concentrations were studied in 20 subjects with primary hyperlipoproteinaemia (16 of type IV, 2 of type II B, 1 of type III). Except for LDL cholesterol maximum effects were obtained with 450 mg daily. Total serum cholesterol and triglycerides (TG) fell significantly. Mean very low density lipoprotein (VLDL) TG fell by 54%. The maximum effect on low density lipoprotein was obtained with 900 mg daily. The effect was highly dependent on initial concentrations, decreases being observed above 4 mmoles/l and increases below that concentration. High density lipoprotein cholesterol increased by 31% (P less than 0.01) independently of the VLDL decrease. Three subjects suffered gastrointestinal side-effects on 1350 mg daily. Only benign reversible changes were noted on non-lipid measurements. Bezafibrate is a well-tolerated drug with a good VLDL TG lowering effect. It is particularly effective in increasing HDL cholesterol concentrations.     

In vivo growth hormone treatment stimulates secretion of very low density lipoprotein by the isolated perfused rat liver.

We have previously demonstrated in hepatocyte suspensions prepared after in vivo GH deprivation [hypophysectomy (hypox)] that rates of esterification of [1-14C]oleic acid into triglyceride (TG) and phospholipid (PL) were diminished, and that these esterification rates were correspondingly restored by repletion with recombinant GH. The current studies were designed to determine if GH exerts a similar effect on the secretion of very low density lipoprotein (VLDL), the primary plasma carrier of TG. We assessed rates of secretion of VLDL lipid and apoprotein by perfused livers prepared from cortisol/T3-replaced hypox female rats in the presence and absence of recombinant human (h) GH infusion. We also determined rates of synthesis and secretion of VLDL TG from infused [1-14C]oleic acid. After hypox, rates of secretion of VLDL lipid (TG, PL, and cholesterol) and apoprotein (total) were significantly decreased. In addition, VLDL secreted under these conditions was depleted of PL, relative to the other lipid components. Secretion of newly synthesized VLDL TG from [1-14C]oleic acid was also decreased; however, neither intracellular accumulation of labeled TG nor absolute tissue levels of TG were significantly changed. Conversely, GH treatment of hypox rats effectively restored rates of secretion of VLDL TG, PL, cholesterol (C) and apoprotein to control levels. These findings support the putative role of GH in regulating VLDL secretion in vivo by demonstrating that alterations in plasma GH are accompanied by changes in VLDL secretion. The findings further suggest that GH may regulate VLDL secretion by altering the amount of PL and/or apoprotein available for formation of the VLDL particle.     

Influence of mild to moderately elevated triglycerides on low density lipoprotein subfraction concentration and composition in healthy men with low high density lipoprotein cholesterol levels

Epidemiologic studies have shown that a dyslipoproteinemia with low concentrations of high density lipoprotein (HDL) cholesterol and elevated serum triglycerides (TG) is associated with a particularly high incidence of coronary artery disease. This lipid profile is associated with increased concentrations of small, dense low density lipoprotein (LDL) particles. To evaluate the role of mild to moderately elevated TG on the LDL subfraction profile in patients with low HDL cholesterol, concentration and composition of six LDL subfractions was determined by density gradient ultracentrifugation in 41 healthy men (31+/-9 years, body mass index (BMI) 25.1+/-3.9 kg/m2) with equally low HDL cholesterol levels < 0.91 mmol/l but different TG levels: TG < 1.13 mmol/l, n = 16; TG = 1.13-2.26 mmol/l, n = 13: TG = 2.26-3.39 mmol/l, n = 12. Those men with moderately elevated TG levels between 2.26 and 3.39 mmol/l had significantly higher concentrations of very low density lipoprotein (VLDL), intermediate low density lipoprotein (IDL), and small, dense LDL apoB and cholesterol than men with TG < 1.13 mmol/l. With increasing serum TG, the TG content per particle also increased in VLDL, IDL as well as total LDL particles while the cholesterol and phospholipid (PL) content decreased in VLDL and IDL, but not in LDL particles. LDL subfraction analysis revealed that only large, more buoyant LDL particles (d < 1.044 g/ml) but not the smaller, more dense LDL, were enriched in TG. Small, dense LDL particles were depleted of free cholesterol (FC) and PL. This study has shown that in men with low HDL cholesterol levels mild to moderately elevated serum TG strongly suggest the presence of other metabolic cardiovascular risk factors and in particular of a more atherogenic LDL subfraction profile of increased concentration of small, dense LDL particles that are depleted in surface lipids.     

内源性高甘油三酯血症患者血浆极低密度脂蛋白、低密度脂蛋白及高密度脂蛋白对血凝及纤维蛋白溶解的影响

研究内源性高甘油三酯血症患者血浆极低密度脂蛋白、低密度脂蛋白及高密度脂蛋白是否发生了氧化修饰及其对凝血及纤维蛋白溶解活性的影响。对 2 1例内源性高甘油三酯血症患者与 2 1例年龄性别相近的正常人的血脂、脂质过氧化物进行了分析。用一次性密度梯度超速离心法分离血浆极低密度脂蛋白、低密度脂蛋白及高密度脂蛋白。测定这 3种脂蛋白的 2 34nm吸光度、相对电泳迁移率和硫代巴比妥酸反应物质含量。分别将这 3种脂蛋白加入由正常人新鲜混合血浆构成的反应系统中 ,按试剂盒分别测定凝血酶原时间、活化部分凝血酶原时间、组织型纤溶酶原激活物活性及纤溶酶原激活物抑制剂 1活性。内源性高甘油三酯血症患者血浆甘油三酯含量平均升高 2 .73倍 ,高密度脂蛋白胆固醇下降 1.71倍 ,同时硫代巴比妥酸反应物质含量升高 1.2 2倍 ;内源性高甘油三酯血症组极低密度脂蛋白、低密度脂蛋白及高密度脂蛋白的 2 34nm吸光度、相对电泳迁移率和硫代巴比妥酸反应物质含量均较对照组显著增加 (P <0 .0 1) ,表明内源性高甘油三酯血症患者血浆极低密度脂蛋白、低密度脂蛋白及高密度脂蛋白均发生了氧化修饰 ,生成了氧化极低密度脂蛋白、氧化低密度脂蛋白及氧化高密度脂蛋白。凝血酶原时间及活化部分凝血酶原时间在分别加入内     

Hypotriglyceridemic effects of levonorgestrel in rats

The progestin, levonorgestrel administered orally to fed female rats significantly lowers both plasma total and very low density lipoprotein triglycerides. In contrast, plasma total cholesterol and low density lipoprotein cholesterol rose significantly. Suspensions of isolated hepatocytes were used to study the effects of levonorgestrel on triglyceride synthesis by examining the incorporation of labelled precursors [( 9,10- 3H]palmitate and [U-14C]glycerol) into triglycerides. Levonorgestrel (10(-4) M) significantly inhibited the incorporation of both precursors into hepatocyte triglycerides and also reduced their incorporation into the triglycerides (nearly all in d less than 1.006) released into the medium. These results suggest that inhibition of hepatic triglyceride synthesis and release can account at least for part of the lowering of plasma VLDL which occurs during administration of levonorgestrel.     

Hepatic delta 9 desaturation and plasma VLDL level in genetically lean and fat chickens.

Plasma VLDL (very low density lipoprotein) content and composition have been investigated in chickens from two lines selected for high or low abdominal fat/live weight ratio, and related to the activity of hepatic delta 9 desaturase. The amounts of plasma VLDL and VLDL-triglycerides (VLDL-TG) were significantly higher in the fat line than in the lean one. Moreover, the chemical composition of VLDL was different between lines, since the greater content of TG in VLDL in the fat birds was associated with lower proportion of all other components. The fatty acid composition of VLDL-TG exhibited differences between lines: palmitoleic acid, which results from hepatic delta 9 desaturation, was in higher proportions in the fat line, whereas linoleic acid was more abundant in the lean one. The activity of liver delta 9 desaturase was significantly higher in the fat animals. A positive correlation between plasma VLDL-TG concentration and hepatic delta 9 desaturase activity in the fat line animals strongly suggests that availability of monoenoic fatty acids is involved in the control of VLDL assembly and secretion. That latter process may explain some of the differences in plasma lipids and in adiposity of the two lines of chickens.     

Metabolism of apolipoprotein B-containing lipoproteins in familial hypercholesterolaemia: effects of plasma exchange.

The turnover of apolipoprotein B (apo B) in very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL) and low density lipoprotein (LDL) was investigated in 2 homozygous and 3 heterozygous patients with familial hypercholesterolaemia. The effects of a marked reduction in plasma LDL concentration, brought about by plasma exchange, upon apo B turnover were studied in 4 patients. Specific activity-time curves for the the plasma apo B after intravenous radioactive VLDL before plasma exchange indicated that in the heterozygotes all IDL-apo B was derived from VLDL and all LDL-apo B was derived from IDL, but the curves from the homozygotes showed that a significant fraction of the LDL in the plasma was not derived from IDL. Plasma exchange did not increase the rates of synthesis of LDL-apo B or VLDL-apo B and had no significant effect on the precursor--product relationship between IDL-apo B and LDL-apo B in heterozygous or homozygous patients. These findings provide no support for the hypothesis that apo B synthesis is controlled by the plasma LDL.