低聚香豆胶磺化衍生物选择清除血浆LDL/Fib的性能研究

以香豆胶为原料,首先进行酸降解,再以氯磺酸为磺化试剂,在适当的条件下进行磺化反应,获得低聚香豆胶磺化衍生物(degraded fenugreek gum sulfate,DFGS)。考察不同磺化条件对硫酸基含量的影响,确立较优磺化反应条件。红外光谱分析表明,该衍生物为新型酸性粘多糖。以低聚香豆胶磺化衍生物为净化剂,研究其选择清除血浆低密度脂蛋白(LDL)及纤维蛋白原(Fib)的性能。结果表明,在pH=5.11,净化剂浓度为1,500mg/L时,可使血浆总胆固醇下降60%～65%,低密度脂蛋白和极低密度脂蛋白下降75%～79%,纤维蛋白原下降近100%,而对高密度脂蛋白及血浆总蛋白水平无显著变化。     

羧甲基降解黄原胶选择性清除血浆LDL/Fib的研究

以黄原胶为原料,进行酸降解,_再以氯乙酸为羧甲基化试剂,在适当的条件下进行羧甲基化反应,获得降解黄原胶羧甲基化衍生物.考察分子质量及酸碱比对产物羧甲基含量的影响,确立较优化的羧甲基化反应条件.并通过红外对结构进行了表征.以降解黄原胶羧甲基化衍生物为净化剂,研究其选择清除血浆中低密度脂蛋白(LDL)及纤维蛋白原(Fib)的性能.结果 表明,在pH=5.20,净化剂浓度为2,500mg/L时,可使血浆总胆固醇(TC)下降40%左右,低密度脂蛋白胆固醇下降45%,纤维蛋白原下降近100%,而总蛋白和高密度脂蛋白(HDL)无明显变化.     

磺化塔拉胶选择清除血浆LDL／Fib的性能研究

该文研究磺化塔拉胶选择性清除血浆低密度脂蛋白（LDL）及纤维蛋白原（Fib）的性能.以塔拉胶为原料,以氯磺酸进行磺化,获得塔批胶磺化衍生物,红外光谱分析表明,该物质为酸性粘多糖,是一种类肝索物质.以磺化塔拉胶为净化剂,研究其选择清除血浆LDL/Fib的性能.结果 表明,当净化体系pH=5.10,净化剂浓度为750mg/L时,可使血浆总胆固醇（TC）平均下降53.4%,低密度脂蛋白和极低密度脂蛋白肌同醇平均下降60.7%,纤维蛋白原平均下降94.7%,而对高密度脂蛋白胆固醇（HDL-C）及血浆总蛋白（TP）水平影响较小.表明磺化塔拉胶是一种选择性良好的血浆LDL/Fib净化剂.     

羧甲基降解瓜胶选择性清除血浆纤维蛋白原和低密度脂蛋白的研究

以瓜胶为原料,进行酸降解,再以氯乙酸为羧甲基化试剂,在适当的条件下进行羧甲基化反应,获得降解瓜胶羧甲基化衍生物。考察分子质量、酸碱比及反应时间对产物羧甲基含量的影响,确立较优的羧甲基化反应条件。并通过红外对结构进行了表征。以降解瓜胶羧甲基化衍生物为净化剂,研究其清除血浆中纤维蛋白原（Fib）及低密度脂蛋白（LDL）~性能。结果表明,在体系pH=5．10,净化剂浓度为1,250mg／L时,可使Fib下降近100％,同时血浆总胆固醇（TC）下降35％左右,低密度脂蛋白胆固醇（LDL）下降42％,而对总蛋白（TP）和高密度脂蛋白（HDL）影响较小。     

双氧水降解卡拉胶选择清除低密度脂蛋白性能的研究

该文以卡拉胶为原料,采用双氧水降解,制备出一种低密度脂蛋白净化剂.考察了净化剂浓度、净化体系pH值对血浆低密度脂蛋白胆固醇(LDL-C)净化效果的影响,得到较优化的诱导沉淀条件.体外间歇诱导沉淀实验表明,该净化剂对血浆总胆固醇(TC)的平均净化率为66.1%,对LDL-C平均净化率为83.7%,对高密度脂蛋白胆固醇(H...     

新型低密度脂蛋白吸附剂的制备及吸附性能初步研究

研究了以壳聚糖为载体,十二胺为疏水基团,3-氯-2-羟基丙磺酸钠为亲水基团的双亲型低密度脂蛋白吸附剂的制备工艺。在此基础上研究和探讨了反应时间、反应温度对吸附剂吸附能力的影响。实验结果初步表明壳聚糖载体在适当条件下进行胺化及磺化修饰之后,可使血浆中的总胆固醇(TC)下降率高达42．11％,低密度脂蛋白胆固醇(LDL)下降高达54．04％,而对高密度脂蛋白(HDL)的吸附率只有10％,具有较高的选择性。     

缺血性脑卒中患者纤维蛋白原和颈动脉斑块的关系

背景纤维蛋白原升高是心脑及周围血管病的独立危险因素,纤维蛋白原及其降解产物大量存在于动脉粥样斑块中,刺激平滑肌细胞增生和迁移而在动脉硬化早期就发挥作用.目的分析血浆纤维蛋白原水平和颈动脉粥样硬化斑块的关系.设计描述性观察.单位上海交通大学医学院附属新华医院神经内科对象为2001-09/12在上海交通大学医学院附属新华医院神经内科的81例缺血性脑卒中患者,男53例,女28例;年龄41～85岁,平均年龄(65±11)岁.方法通过颈动脉超声检查,将81例缺血性卒中患者分成颈动脉有斑块组和无斑块组,检查两组患者的血浆纤维蛋白原水平、血清总胆固醇、低密度脂蛋白胆固醇及其他动脉粥样硬化的危险因素.观察各危险因素指标与颈动脉斑块的关系.主要观察指标颈动脉硬化的各项危险因素指标,颈动脉斑块.结果81例缺血性脑卒中患者全部进入结果分析.①颈动脉有斑块组(45例)纤维蛋白原、总胆固醇、低密度脂蛋白胆固醇分别为(4.38±1.33)g/L;(5.19±1.27)mmol/L;(3.15±0.73)mmol/L,高于无斑块组(36例)(3.20±1.30)g/L;(4.56±1.30)mmol/L;(2.49±0.92)mmol/L,P＜0.05).②颈动脉斑块在纤维蛋白原低、中、高三组中的比例分别为11%(5例)、16%(7例)、73%(33例),差异有显著性意义(P=0.02).③颈动脉硬化的多因素分析表明,糖尿病、低密度脂蛋白、纤维蛋白原和年龄水平增高是颈动脉粥样斑块形成的危险因素.结论纤维蛋白原在动脉粥样硬化斑块发生发展过程中起重要作用.     

血浆纤维蛋白原水平的影响因素及其临床意义

目的探讨遗传与环境因素对血浆纤维蛋白原水平的影响;研究血浆纤维蛋白原在冠心病发病中的作用.方法从正常查体人员中随机选择105例血浆纤维蛋白原水平大于4 g/L者作为实验组,在同一人群中按年龄、性别11配比的原则,选择血浆纤维蛋白原水平小于4 g/L者作为对照组;深入现场,检测可能与血浆纤维蛋白原水平有关的因素,采用条件Logistic回归分析研究各因素对血浆纤维蛋白原水平的影响;并随访比较了不同血浆纤维蛋白原水平者一级亲属的血浆纤维蛋白原水平和心血管疾病的发生情况.结果体重指数,高脂肪饮食,吸烟,体力活动少,高血压,甘油三酯,高密度脂蛋白,低密度脂蛋白,一级亲属的血浆纤维蛋白原水平等9个因素进入回归方程;高纤维蛋白原者的一级亲属(6.1±0.8 g/L)明显高于低纤维蛋白原者的一级亲属的(4.4±0.5 g/L);血浆纤维蛋白原浓度高者CHD的发病率(24%)高于血浆纤维蛋白原低者(10%).结论遗传和环境因素均对血浆纤维蛋白原水平有一定的影响;血浆纤维蛋白原浓度升高是CHD发病的独立危险因素.     

血浆D-二聚体与急性冠脉综合征关系的研究

急性冠脉综合征（acute coronary syndrome,ACS）发病率高,致死、致残率高,早期识别及早期治疗,能明显降低死亡率,改善预后.血浆DD存在于因子ⅩⅢa交联纤维蛋白（XDP）纤溶酶降解过程中形成的可溶性衍生物,这些可溶性纤维蛋白原降解产物包括一种纤维蛋白原分子中没有的新抗原（D-二聚体结构,以及它的降解产物和可溶的纤维蛋白原.增高的DD表明体内有血栓形成和或血栓正在溶解.本文旨在探讨ACS及血浆DD的关系及与ACS危险程度的相关性.     

脑梗死患者颈动脉粥样硬化的危险因素分析

目的 探讨脑梗死患者颈动脉粥样硬化程度与血脂、纤维蛋白原、血糖、血尿酸及C反应蛋白的关系.方法 将122例脑梗死患者按颈动脉硬化程度分为内膜中膜增厚组、斑块形成组和管腔狭窄组,分别测定其与56例对照组的总胆固醇、三酰甘油、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、载脂蛋白A、载脂蛋白B、脂蛋白(a)、纤维蛋白原、血糖、血尿酸及C反应蛋白水平,观察颈动脉粥样硬化程度与血脂、纤维蛋白原、血糖、血尿酸及C反应蛋白的关系.结果 斑块形成组和管腔狭窄组三酰甘油、低密度脂蛋白胆固醇、载脂蛋白B、纤维蛋白原、血糖、血尿酸及C反应蛋白水平显著高于内膜中膜增厚组和对照组(P<0.05).内膜中膜增厚组三酰甘油、低密度脂蛋白胆固醇、载脂蛋白B、纤维蛋白原、血糖、血尿酸及C反应蛋白水平显著高于对照组(P<0.05).Logistic多元回归分析发现,颈动脉粥样硬化程度与低密度脂蛋白胆固醇、脂蛋白(a)、纤维蛋白原、血糖、血尿酸呈显著正相关(P<0.05～0.01).结论 低密度脂蛋白胆固醇、脂蛋白(a)、纤维蛋白原、血糖、血尿酸是颈动脉粥样硬化的独立危险因素.及时检测脑梗死患者血脂、纤维蛋白原、血糖、血尿酸、C反应蛋白和颈动脉粥样硬化情况,评价病变程度,对疾病的早期防治具有重要的价值.     

Treatment of hypercholesterolemia by precipitation of lipoproteins with dextran sulfate

An on-line continuous system for the selective precipitation of low-density lipoproteins (LDL) and very low-density lipoproteins (VLDL) has been devised and tested. This system conserves high-density lipoproteins (HDL) and other plasma macromolecules. LDL and VLDL are precipitated from plasma using 10-35 mg/dl dextran sulfate (Mr 5,000) in the presence of 55 mM calcium with a reduced concentration of monovalent cations. The plasma is obtained by membrane filtration of whole blood using the COBE Centry TPE System (Cobe Laboratories Inc, Lakewood, Co.). The precipitated LDL plus VLDL is removed by filtration, and the electrolytes are restored by dialysis. The plasma minus LDL plus VLDL is then returned to the patient. Four patients with heterozygous familial hypercholesterolemia (type II) were treated 70 times. The mean pretreatment serum cholesterol was 383 mg/dl. The mean reductions in plasma components were: LDL plus VLDL 63%; HDL 27%; fibrinogen 19%; albumin 15%; IgG 20%; IgA 19%; IgM 25%; C3 30%; and C4 27%. The cholesterol returned to near normal values in approximately 2 weeks after each treatment. Four normal volunteers were each treated one time. These individuals had a mean pretreatment serum cholesterol of 201 mg/dl. The mean reduction in plasma components were: LDL plus VLDL 70%; HDL 27%; fibrinogen 24%; albumin 14%; IgG 18%; IgA 17%; IgM 20%; C3 27%; C4 22%; C3 proactivator 12%; alpha 1-antitrypsin 17%; ceruloplasma 17%; transferrin 18%; alpha 2-macroglobulin 17%; and orosomucoid 13%. It is our conclusion that dextran sulfate precipitation is an effective on-line means of selectively removing LDL plus VLDL from plasma while conserving HDL and other plasma macromolecules.(ABSTRACT TRUNCATED AT 250 WORDS)     

Reduction of low-density lipoproteins with dextran sulfate in patients with familial hypercholesterolemia

A novel on-line system for the selective precipitation of low-density lipoprotein (LDL) using dextran sulfate has been devised and tested in four patients with heterozygous familial hypercholesterolemia (type II). The mean pretreatment serum cholesterol was 410 mg/dl. Plasma was generated by membrane filtration and LDL and VLDL (very-low-density lipoprotein) were completely precipitated with 10-35 mg% dextran sulfate (Mr 5,000) in the presence of 55 mM Ca2+. The precipitate was removed by filtration and the excess Ca2+ by dialysis. For 41 procedures the mean reduction of plasma solutes was LDL + VLDL 65%, HDL 23%, fibrinogen 19%, albumin 15%, IgG 20%, IgA 19%, IgM 24%. We conclude that dextran sulfate precipitation is an effective method for selective on-line removal of LDL from plasma.     

Liver heparan sulfate proteoglycans mediate clearance of triglyceride-rich lipoproteins independently of LDL receptor family members

We examined the role of hepatic heparan sulfate in triglyceride-rich lipoprotein metabolism by inactivating the biosynthetic gene GlcNAc N-deacetylase/N-sulfotransferase 1 (Ndst1) in hepatocytes using the Cre-loxP system, which resulted in an approximately 50% reduction in sulfation of liver heparan sulfate. Mice were viable and healthy, but they accumulated triglyceride-rich lipoprotein particles containing apoB-100, apoB-48, apoE, and apoCI-IV. Compounding the mutation with LDL receptor deficiency caused enhanced accumulation of both cholesterol- and triglyceride-rich particles compared with mice lacking only LDL receptors, suggesting that heparan sulfate participates in the clearance of cholesterol-rich lipoproteins as well. Mutant mice synthesized VLDL normally but showed reduced plasma clearance of human VLDL and a corresponding reduction in hepatic VLDL uptake. Retinyl ester excursion studies revealed that clearance of intestinally derived lipoproteins also depended on hepatocyte heparan sulfate. These findings show that under normal physiological conditions, hepatic heparan sulfate proteoglycans play a crucial role in the clearance of both intestinally derived and hepatic lipoprotein particles.     

Determination of high-density lipoproteins: screening methods compared.

Factors reflecting the concentration of high-density lipoproteins in serum were assessed for 108 men and 106 women participating in a Venetian screening program for hyperlipoproteinemia. The methods applied, optimized in our laboratory, were: (a) cholesterol in high-density lipoproteins, determined in the supernate after sedimentation of the very-low-density lipoproteins + low-density lipoproteins with dextran sulfate or sodium phosphotungstate; and (b) immunochemical quantitation of apolipoprotein A-I and apolipoprotein A-II by Laurell's "rocket" technique. The latter determinations were performed with total serum before and after delipidation with diispropyl ether/n-butanol (6/4 by vol). The dextran sulfate method gave about 5% higher values than did the phosphotungstate method, but the correlation between the two was excellent (r = 0.95). Results of the immunochemical quantitation indicate that delipidation of lipoproteins before Laurell electrophoresis may not be necessary if only freshly drawn sera are used.     

Precipitation methods for the determination of LDL-cholesterol

The selective precipitation of low-density lipoproteins (LDL) with polyvinyl sulfate (PVS), and the immunoprecipitation of high-density lipoproteins (HDL) and very-low-density lipoproteins (VLDL) with an anti-HDL antibody, can both be used to establish simple methods for the determination of LDL cholesterol. Whereas the PVS method requires the calculation of LDL cholesterol as the difference of total and supernatant cholesterol, the immunoprecipitation method allows the direct measurement of LDL cholesterol in the supernatant. As a first step, both methods were optimized to yield accurate values for normolipemic and slightly hyperlipemic serum samples. Moreover, the determination of LDL-cholesterol in lipemic sera can be achieved by a combination of immunoprecipitation and polyanion precipitation.     

An increase in micropulmonary red cell mass in hyperlipidaemic patients

Summary. It is known that pulmonary microcirculation rheology is partly affected by plasma levels of lipoproteins, but only a few data are available for humans. Therefore, in a sample of 30 normal volunteers and 90 patients with various types of primary hyperlipoproteinaemia, the plasma levels of total cholesterol (Choi), low density cholesterol (LDL), the high density cholesterol (HDL), triglyceride (Tg) and fibrinogen (Fib) were measured in conjunction with determinations of plasma viscosity (PV) and the pulmonary capillary red cell volume (RCV_C). RCV_C was estimated from measurements of the vascular component of the single-breath-diffusing lung capacity for carbon monoxide, using our own modification of the Roughton-Forster's method. By stepwise regression analysis, the variation in RCV_C was almost completely accounted for (r²=0.87) by variations in PV, Choi, Tg and the anthropometric confounding factors. The proposed explanations for increased pulmonary capillary red cell mass (up to 151 % of the predicted value) in hyperlipidaemic patients included the hypothesis of increased pulmonary microhaematocrit, which agrees with the observed in-vitro lipoprotein-dependent increase in erythrocyte aggregability.     

Dual-precipitation method evaluated for determination of high-density lipoprotein (HDL), HDL2, and HDL3 cholesterol concentrations

We evaluated a dual-precipitation method for determining cholesterol in high-density lipoprotein (HDL) and its subfractions HDL2 and HDL3. After total HDL was isolated by precipitation of very-low-density (VLDL) and low-density (LDL) lipoproteins with polyethylene glycol (Mr 8000), HDL2 was isolated from total HDL by precipitation with dextran sulfate (Mr 15,000), leaving HDL3 in the supernate. Concentration of total HDL cholesterol after precipitation of VLDL and LDL with PEG showed significant proportional and constant biases of -3.8% and 0.04 mmol/L, respectively, when compared with a phosphotungstic acid-based comparison method, although results by the two methods were correlated highly (r = 0.99, P less than 0.001). HDL2 and HDL3 cholesterol concentrations measured with the present technique were not different from those obtained by density-gradient ultracentrifugation or by combined precipitation-ultracentrifugation.