甘露聚糖、壳聚糖、α-酸性糖蛋白和姜黄素对脂蛋白(a)和去唾液酸脂蛋白(a)代谢影响的对比分析

分析多糖和姜黄素对脂蛋白（ａ）和去唾液酸脂蛋白（ａ）和去唾液酸脂蛋白（ａ）代谢的影响,从刺猥腋下静脉注入甘露聚糖、壳聚糖、α－酸性糖蛋白和姜黄素,２ｍｉｎ后注射＾１２５Ｉ－脂蛋白（ａ）或＾１２５Ｉ－去唾液酸脂蛋白（ａ）,１ｈ后处死动物,测定血、肝、肾、脾、胆汁和肾上腺的同位素含量。结果发现,脂蛋白（ａ）去唾液酸后能大量进入肝脏,加速在体内的分解代谢,使血中浓度迅速降低。α－酸性糖蛋白抑制组织对脂蛋白（ａ）和去唾液酸脂蛋白（ａ）的摄入,使血中脂蛋白（ａ）和去唾液酸脂蛋白（ａ）含量显著增高。壳聚糖和姜黄素增加肝脏和肾上腺对脂蛋白（ａ）的摄取,使血中脂蛋白（ａ）含量略降低,但对去唾液酸脂蛋白（ａ）代谢无明显影响。甘露聚糖增加脾脏对脂蛋白（ａ）的摄取,减少胆囊中脂蛋白（ａ）含量,但增加肾脏和胆囊对去唾液酸脂蛋白（ａ）的     

胱硫醚β-合酶活性的测定及应用

为探讨姜黄素的降血脂和抗动脉粥样硬化作用是否通过影响低密度脂蛋白和脂蛋白（ａ）的代谢来实现的,用姜黄素经刺猥腋下静脉注入,２ｍｉｎ后注射＾１２５Ｉ－低密度脂蛋白、＾１２５Ｉ－低密度脂蛋白、＾１２５Ｉ－脂蛋白（ａ）、＾１２５Ｉ－去唾液酸低密度脂蛋白或＾１２５Ｉ－去唾液酸脂蛋白（ａ）,１小时后处死动物,测定血、肝、肾、脾、胆汁和肾上腺中的放射性含量。实验发现,姜黄素使低密度脂蛋白进入肝脏和肾上腺增多胆     

去唾液酸对低密度脂蛋白和脂蛋白(a)代谢的影响

将低密度脂蛋白和脂蛋白（ａ）用神经氨酸酶处理，去除低密度脂蛋白（ａ）中所含末端唾液酸，然后用＾１２５Ｉ－纤维素二糖酪胺标记，经刺猬腋下静脉注射，分别于３ｈ和６ｈ处死，测定血，肝，脾，肾和胆汁中放射含量，分析和比较去唾液酸和富含唾液酸低密度脂蛋白和脂蛋白（ａ）的代谢变化，实验发现，注射去唾液酸低密度脂蛋白的最初３ｈ，组织内的代谢速率低于低密度脂蛋白组，后６ｈ后代谢速率则高于低密度脂蛋白组。注射去唾液     

脂蛋白(a)的研究进展

脂蛋白(a)是动脉粥样硬化形成与进展的高危因素,外周血中高浓度的脂蛋白(a)已成为冠心病公认的预测因子。由于它主要受遗传调控,饮食、运动、生活方式、传统降脂药物等对脂蛋白(a)水平的影响很小。随着研究的深入,脂蛋白(a)的代谢、致病机制和危害逐渐被人们了解,氧化修饰后的脂蛋白(a)具有更强的致动脉粥样硬化作用。此外,可降低脂蛋白(a)的新型降脂药物已经被研发出来,它们降低脂蛋白(a)的强度和作用靶点各不相同,对疾病的预后的影响也仍有待观察。本文就脂蛋白(a)的代谢、遗传调控、氧化修饰、临床干预手段等研究进展作一综述。     

脂蛋白(a):脂蛋白代谢与血栓形成的潜在联系

脂蛋白(a),1963年始被提出。其浓度因人而异,多数人浓度低。临床研究证明,脂蛋白(a)浓度增加的人对冠脉疾病敏感性增高。脂蛋白(a)是低密度脂蛋白(LDL)中唯一的蛋白成分,其本质是大分子糖蛋白即载脂蛋白(a)结     

低密度脂蛋白受体抑制剂对低密度脂蛋白和脂蛋白(a)代谢的影响

应用低密度脂蛋白受体抑制剂乳酸杆褐质和受体结构蛋白经刺猬腋下静脉注入，２ｍｉｎ后注射＾１２５Ｉ－低密度脂蛋白或＾１２５Ｉ－脂蛋白（ａ），６ｈ后处死，测定血，肝，肾，脾，胆汁和肾上腺的放射活性，实验发现，乳酸肝褐质和受体结合蛋白均能抑制低密度脂蛋白受体活性，使各组织摄取低密度脂蛋白分别降低１５％～８６％以上，但乳酸肝褐质和受体结构蛋白脂蛋白（ａ）的组织摄取不但无抑制作用，反而能使脂蛋白（ａ）进入组织     

脂蛋白(a)分解代谢研究进展

脂蛋白（ａ）分子结构中除载脂蛋白Ｂ以外,还含有载脂蛋白（ａ）,载脂蛋白（ａ）与纤溶酶原高度同源,它参与了血管壁的脂质沉积和血栓形成两个过程,是心脑血管病独立的危险因子。目前虽然对脂蛋白（ａ）结构了解得比较清楚,但对其病理生理学意义,特别是它的分解代谢途径了解甚少。有人认为脂蛋白（ａ）中含有载脂蛋白Ｂ,所以主要经低密度脂蛋白受体途径代谢;但由于脂蛋白（ａ）中的载脂蛋白Ｂ与载脂蛋白（ａ）结合形成二硫键,使空间构象发生改变,因此有人认为脂蛋白（ａ）是低密度脂蛋白受体的不良配体,只有当脂蛋白（ａ）分子内部的二硫键被打开,使载脂蛋白Ｂ从脂蛋白（ａ）中解离出来,脂蛋白（ａ）部分才能恢复与低密度脂蛋白受体的亲和力;甚至有学者认为脂蛋白（ａ）根本不通过低密度脂蛋白受体途径代谢,而且脂蛋白（ａ）还可能有促进低密度脂蛋白代谢的作用     

脑梗死病人血尿酸、脂蛋白(a)含量的研究

目的探讨脑梗死病人血尿酸(UA)、血清脂蛋白(a)[Lp(a)]含量的变化及其意义.方法对85例脑梗死病人测定其血总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白(LDL-C)、高密度脂蛋白(HDL-C)、脂蛋白(a)及血尿酸水平.并与对照组(40例)进行对比观察.结果脑梗死病人TC、TG、HDL-C水平与对照组相比无统计学意义(P＞0.05),UA、LDL-C、Lp(a)水平较对照组明显升高(P＜0.01);其中脑梗死合并糖尿病者较无糖尿病者血UA、Lp(a)亦有明显升高(P＜0.05),两组与正常对照组比较有统计学意义(P＜0.05).结论血尿酸、Lp(a)含量增高与脑梗死存在一定关系,是脑梗死的重要危险因素.     

脑梗死患者脑脊液和血清中脂蛋白(a)的变化

为观察脑梗死患者脑脊液和血清中脂蛋白 (a)含量的变化 ,选择 80例脑梗死患者和 40例对照者 ,用酶联免疫法测定脂蛋白 (a)在脑脊液及血清中的含量。结果发现 ,脑梗死患者与对照者脑脊液中脂蛋白 (a)含量分别为 2 34± 2 9μg/L及 2 11± 2 1μg/L ,血清中脂蛋白 (a)含量分别为 0 .2 99± 0 .0 2 8g/L及 0 .2 71± 0 .0 2 5g/L ,脑梗死组脑脊液及血清中脂蛋白 (a)含量明显高于对照组 (P <0 .0 1)。脑梗死患者和对照者脑脊液与血清中脂蛋白 (a)水平间均无相关关系 (P >0 .0 5 )。结果提示 ,脑梗死患者脑脊液及血清中脂蛋白 (a)水平明显高于对照者。     

脂蛋白(a)测定的标准化和在心血管疾病中的价值

简述脂蛋白(a)测定国际标准化程序和存在的问题。载脂蛋白(a)分子大小的不均一性不同程度地影响免疫化学测定,使脂蛋白(a)测定标准化不易推广和应用,同时脂蛋白(a)测定值的不准确性影响评估个体心血管疾病危险状态。文章综合分析了国内外冠心病和脑卒中与脂蛋白(a)水平的关系。国内报道的病例—对照结果均指示冠心病和脑卒中患者的脂蛋白(a)增高,而且脂蛋白(a)水平与冠状动脉狭窄程度相关。国外前瞻性报告亦证实冠心病患者脂蛋白(a)增高,但是对脂蛋白(a)是否为脑卒中的危险因素尚有争论。文章讨论了脂蛋白(a)测定的指征及其在心血管疾病的预防和治疗中的价值。     

The in vivo metabolism of recombinant human erythropoietin in the rat

We compared the in vivo plasma clearance and organ accumulation in anesthetized rats of 125I-labeled, recombinant human erythropoietin and 125I-labeled, desialylated recombinant erythropoietin. The immediate volume of distribution of 125I-labeled, recombinant erythropoietin approximated that of the plasma volume. Its plasma clearance was multiexponential, with an initial rapid distribution phase (t1/2 = 53 minutes) and a slower elimination phase (t1/2 = 180 minutes). Organ accumulation of labeled recombinant erythropoietin, as compared with 125I-labeled human albumin, was negligible until 30 minutes after injection when small amounts appeared in the kidneys and bone marrow. Only 24% of the 125I-labeled, desialylated recombinant erythropoietin was recovered immediately after injection, and 96% of the hormone was cleared from the plasma with a t1/2 of 2.0 minutes. The bulk of the desialylated hormone accumulated in the liver where it was rapidly catabolized and its breakdown products released back into the plasma. Significantly, in contrast to unmodified erythropoietin, there was also early accumulation of desialylated hormone in the kidneys, marrow, and spleen. Desialylated orosomucoid but not orosomucoid, yeast mannan, or dextran sulfate 500 inhibited the rapid plasma clearance and hepatic accumulation of desialylated erythropoietin. Oxidation of the desialylated hormone restored its plasma recovery and clearance to normal but rendered it biologically inactive, and accumulation in organs other than the kidney was negligible.     

The major insect lipoprotein is a lipid source to mosquito stages of malaria parasite

Once mosquito midgut barrier was crossed malaria parasite faces a extensive metabolic developmental program in order to ensure its transmission. In the hemolymph of the mosquito the dynamics of lipid metabolism is conducted by a major lipoprotein, lipophorin (Lp). It was recently shown that Lp is engaged in the mosquito immune response to parasite infection. However, it is not clear if Lp is uptaken by the parasite. Here, we show that oocysts are able to uptake mosquito Lp. The uptake of FITC-labeled Lp was demonstrated in midgut-associated oocysts. Alternatively, to confirm Lp incorporation by oocysts we have conducted another set of experiments with iodinated Lp (¹²⁵I-Lp). Oocysts were able to incorporate ¹²⁵I-Lp and the process is both time and temperature dependent. This set of results indicated that no matter oocysts are attached to mosquito midgut wall they bear a lipid sequestering machinery from its surroundings. Phospholipid transfer to sporozoites was also demonstrated. In conclusion, these results demonstrate for the first time that malaria parasite undergoes lipid uptake while in the invertebrate host.     

天然及氧化型脂蛋白(a)与巨噬细胞表面结合

为探讨脂蛋白 (a)及氧化型脂蛋白 (a)在巨噬细胞上的结合和降解途径 ,将生物素标记的脂蛋白与小鼠腹腔巨噬细胞进行结合和竞争性结合试验。结果发现 ,脂蛋白 (a)能以一定的亲和力、可饱和性地与巨噬细胞表面结合 ;低密度脂蛋白对其结合无明显抑制作用 ,而氧化型低密度脂蛋白、氧化型脂蛋白 (a)均能不同程度地抑制这种结合。脂蛋白 (a)经氧化修饰后 ,与巨噬细胞的结合量显著增加。脂蛋白 (a)、低密度脂蛋白不能有效竞争氧化型脂蛋白 (a)的结合 ,而氧化型脂蛋白 (a)和氧化型低密度脂蛋白为有效的竞争性抑制剂。提示脂蛋白 (a)主要经清道夫受体与巨噬细胞表面结合 ;氧化型脂蛋白 (a)除经清道夫受体介导外 ,可能还通过其它特异性受体与巨噬细胞表面结合。     

Lipoprotein (a)

The lipids are transported by lipoproteins in the blood system. Lipoprotein (a) [Lp (a)] is a unique lipoprotein of the human plasma discovered by professor Berg in 1963. Lp (a) consists of apolipoprotein (a) and LDL particles (apolipoprotein B100). The level and size of Lp (a) are highly variable and largely determined heredity. Clinical studies on animal models have shown that elevated Lp (a) levels are linked with a higher risk of atherosclerosis, even though not all of the conclusions based on the studies that have been carried are convincing. Concentration over 35 mg/dl is considered to be a risk level. Surprisingly high Lp (a) levels in old age are associated with longevity. This may be explained by the physiological role of Lp (a) in tissue reparation, wound healing and anti-cancer effect.     

Selective hepatic uptake of human β-hexosaminidase A by a specific glycoprotein recognition system on sinusoidal cells

Intravenously administered (125)I-labeled human beta-hexosaminidase A (beta-N-acetylglucosaminidase; 2-acetamido-2-deoxy-beta-D-glucoside acetamidodeoxyglucohydrolase, EC 3.2.1.30) was rapidly cleared from the circulation of rats and accumulated in the liver. When hepatic cells were subsequently isolated, the label was recovered from both sinusoidal cells and, to a lesser extent, hepatocytes. Clearance was inhibited by the simultaneous infusion of mannan but not by a galactose-terminated glycoprotein. Studies in vitro, in which (125)I-beta-hexosaminidase was incubated with isolated hepatic cells, detected no uptake of the labeled ligand by hepatocytes. In contrast, uptake by sinusoidal cells was shown to be temperature dependent and approached saturability. Prior treatment of sinusoidal cells with Pronase resulted in markedly decreased uptake of (125)I-beta-hexosaminidase by these cells. Mannan and partially deglycosylated glycoproteins bearing terminal nonreducing N-acetylglucosamine or mannose residues were shown to be potent inhibitors of the cellular uptake of (125)I-beta-hexosaminidase; native orosomucoid and desialylated (galactoseterminated) orosomucoid were not inhibitory. Of six simple sugars tested, including N-acetylglucosamine, only mannose was an effective inhibitor of the cellular uptake of (125)I-beta-hexosaminidase. The kinetics of uptake of beta-hexosaminidase and mannose-terminated orosomucoid by sinusoidal cells were shown to be similar. These findings suggest that the hepatic uptake of the lysosomal glycosidase beta-hexosaminidase A is mediated by a receptor on sinusoidal cells which recognizes and binds mannose-terminated glycoproteins.     

Lipoprotein (a) levels, apolipoprotein (a) phenotypes and thyroid autoimmunity

It has been reported that euthyroid normolipidemic males and postmenopausal females exhibit significantly higher serum lipoprotein (a) (Lp(a)) levels compared with age- and sex-matched normolipidemic controls. However, it is well known that there is an inverse correlation between Lp(a) concentration and apolipoprotein (a) (apo(a)) isoform size. Thus, it is imperative to exclude differences in apo(a) isoform frequencies between subjects with or without thyroid autoimmunity in order to verify if there is an association between thyroid autoimmunity and increased Lp(a) concentration. To exclude such an effect of different apo(a) isoform frequencies, we determined apo(a) phenotypes in 22 patients (9 males and 13 postmenopausal females) with thyroid autoimmunity and in 64 (29 males and 35 females) age- and sex-matched individuals without thyroid autoimmunity (control group). There were no significant differences in the values of lipid parameters between the two groups, including Lp(a). We did not detect any significant differences in the apo(a) phenotype frequencies between the two groups. Additionally, in neither of the subgroups formed according to the presence of low molecular vs high molecular weight apo(a) isoforms were there any significant differences in median serum Lp(a) levels between patients with and without thyroid autoimmunity. Thus, our results contradict the previously reported association between thyroid autoimmunity and Lp(a) concentrations.     

Lipoprotein (a), lipids, and lipoproteins in patients with rheumatoid arthritis.

Lipoprotein (a), (Lp(a)), an independent atherogenic factor, was significantly increased in 93 patients with classical, seropositive rheumatoid arthritis of median disease activity. In the patients with Lp(a) concentrations above the upper reference value of 480 mg/l there was a significant correlation between Lp(a) and the concentration of orosomucoid, erythrocyte sedimentation rate, and the platelet count. The plasma concentrations of cholesterol and high density lipoprotein-cholesterol in both male and female patients were significantly lower than in controls. Apolipoprotein B and apolipoprotein AI in the patients correlated significantly with total cholesterol and high density lipoprotein-cholesterol respectively.