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脂质和脂蛋白[低密度脂蛋白-脂蛋白(a)] 分离术。最新进展。

The lipid- and lipoprotein- [LDL-Lp(a)] apheresis techniques. Updating.

作者信息

Stefanutti C, Morozzi C, Perrone G, Di Giacomo S, Vivenzio A, D'Alessandri G

机构信息

Sapienza University of Rome, Rome, Italy.

出版信息

G Chir. 2012 Nov-Dec;33(11-12):444-9.

Abstract

Therapeutic plasmapheresis allows the extracorporeal removal of plasmatic lipoproteins (Lipid-apheresis) (LA). It can be non selective (non specific), semi - selective or selective low density lipoprotein-lipoprotein(a) (specific [LDL- Lp(a)] apheresis) (Lipoprotein apheresis, LDLa). The LDL removal rate is a perfect parameter to assess the system efficiency. Plasma-Exchange (PEX) cannot be considered either specific nor, selective. In PEX the whole blood is separated into plasma and its corpuscular components usually through centrifugation or rather filtration. The corpuscular components mixed with albumin solution plus saline (NaCl 0.9%) solution at 20%-25%, are then reinfused to the patient, to substitute the plasma formerly removed. PEX eliminates atherogenic lipoproteins, but also other essential plasma proteins, such as albumin, immunoglobulins, and hemocoagulatory mediators. Cascade filtration (CF) is a method based on plasma separation and removal of plasma proteins through double filtration. During the CF two hollow-fiber filters with pores of different diameter are used to eliminate the plasma components of different weight and molecular diameter. A CF system uses a first polypropylene filter with 0.55 µm diameter pores and a second one of diacetate of cellulose with 0.02 µm pores. The first filter separates the whole blood, and the plasma is then perfused through a second filter which allows the recovery of molecules with a diameter lower than 0.02 µm, and the removal of molecules larger in diameter as apoB100-containing lipoproteins. Since both albumin and immunoglobulins are not removed, or to a negligible extent, plasma-expanders, substitution fluids, and in particular albumin, as occurs in PEX are not needed. CF however, is characterized by lower selectivity since removes also high density lipoprotein (HDL) particles which have an antiatherogenic activity. In the 80's, a variation of Lipid-apheresis has been developed which allows the LDL-cholesterol (LDLC) (-61%) and Lp(a) (-60%) removal from plasma through processing 3 liters of filtered plasma by means of lipid-specific thermofiltration, LDL immunoadsorption, heparin-induced LDL precipitation, LDL adsorption through dextran sulphate. More recently (90's) the DALI®, and the Liposorber D® hemoperfusion systems, effective for apoB100- containing lipoproteins removal have been developed. All the above mentioned systems are established LDL-apheresis techniques referable to the generic definition of LDLa. However, this last definition cannot describe in an appropriate manner the removal of another highly atherogenic lipoprotein particle: the Lp(a). Thus it would be better to refer the above mentioned techniques to the wider scientific and technical concept of lipoprotein apheresis.

摘要

治疗性血浆置换可实现血浆脂蛋白的体外清除(脂质分离)(LA)。它可以是非选择性的(非特异性的)、半选择性的或选择性低密度脂蛋白-脂蛋白(a)(特异性[LDL-Lp(a)]分离)(脂蛋白分离,LDLa)。低密度脂蛋白清除率是评估该系统效率的理想参数。血浆置换(PEX)既不能被认为是特异性的,也不是选择性的。在血浆置换中,全血通常通过离心或过滤被分离成血浆及其细胞成分。细胞成分与20%-25%的白蛋白溶液加生理盐水(0.9%氯化钠)溶液混合后,再回输给患者,以替代先前去除的血浆。血浆置换可清除致动脉粥样硬化脂蛋白,但也会清除其他重要的血浆蛋白,如白蛋白、免疫球蛋白和血液凝固介质。级联过滤(CF)是一种基于血浆分离并通过双重过滤去除血浆蛋白的方法。在级联过滤过程中,使用两个孔径不同的中空纤维滤器来清除不同重量和分子直径的血浆成分。一个级联过滤系统使用第一个孔径为0.55 µm的聚丙烯滤器和第二个孔径为0.02 µm的醋酸纤维素滤器。第一个滤器分离全血,然后血浆通过第二个滤器,第二个滤器可回收直径小于0.02 µm的分子,并去除直径较大的分子,如含载脂蛋白B100的脂蛋白。由于白蛋白和免疫球蛋白都不会被清除,或清除程度可忽略不计,因此不需要像血浆置换那样使用血浆扩容剂、置换液,尤其是白蛋白。然而,级联过滤的特点是选择性较低,因为它也会清除具有抗动脉粥样硬化活性的高密度脂蛋白(HDL)颗粒。在20世纪80年代,开发了一种脂质分离的变体方法,通过脂质特异性热过滤、低密度脂蛋白免疫吸附、肝素诱导的低密度脂蛋白沉淀、通过硫酸葡聚糖吸附低密度脂蛋白等方法,从3升过滤后的血浆中去除低密度脂蛋白胆固醇(LDLC)(-61%)和脂蛋白(a)(-60%)。最近(20世纪90年代),开发了DALI®和Liposorber D®血液灌流系统,它们对清除含载脂蛋白B100的脂蛋白有效。上述所有系统都是公认的低密度脂蛋白分离技术,可归为LDLa的一般定义。然而,最后这个定义不能恰当地描述另一种高度致动脉粥样硬化的脂蛋白颗粒:脂蛋白(a)的清除。因此,将上述技术归为更广泛的脂蛋白分离科学技术概念会更好。

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