Lee Diana M, Knight-Gibson Carolyn, Samuelsson Ola, Attman Per-Ola, Wang Chi-Sun, Alaupovic Petar
Department of Obstetrics & Gynecology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA.
Kidney Int. 2002 Jan;61(1):209-18. doi: 10.1046/j.1523-1755.2002.00116.x.
Increased concentrations of very low- (VLDL) and intermediate-density (IDL) lipoproteins in chronic renal failure (CRF) are thought to result from a defect(s) in degradation of plasma triglyceride (TG)-rich lipoproteins. The purpose of this study was to identify lipoprotein abnormalities associated with the reduced lipolytic rate constant, k1, of combined VLDL and IDL substrate from renal patients and asymptomatic controls.
The VLDL + IDL were isolated from 18 predialytic patients (CRF-I), 8 patients on hemodialysis (CRF-II) and 10 asymptomatic controls. The lipolytic rate constant (k1) of VLDL + IDL was measured by an assay using bovine milk lipoprotein lipase and determination of TG before and after incubation by gas chromatography (GC). Neutral lipids were measured by GC and apolipoproteins by electroimmunoassays; the apolipoprotein-defined TG-rich lipoproteins including Lp-B:C, Lp-B:C:E and Lp-A-II:B:C:D:E were determined by immunoaffinity chromatography.
The k1 values of VLDL + IDL were significantly (P < 0.001) lower in CRF-I and CRF-II patients (0.0341 and 0.0352 min-1, respectively) than controls (0.0515 min-1). The levels of apolipoproteins B, C-III and E, and TG-rich Lp-B:C, Lp-B:C:E and Lp-A-II:B:C:D:E particles normalized to 100 mg TG per VLDL + IDL were significantly higher in both groups of CRF patients than in controls. All three TG-rich lipoproteins were characterized by significantly increased percent contents of free (FC) and esterified (CE) cholesterol and a decreased percentage of TG. The k1 values of the combined CRF-I and CRF-II patient groups showed significant negative correlations (P < 0.001) with FC (r=-0.81) and CE (r=-0.63) and a positive correlation with TG (r=0.72). Among lipoprotein particles, only Lp-A-II:B:C:D:E levels showed a significant negative correlation with k1 values (r=-0.47, P < 0.03).
This study shows that the abnormal neutral lipid composition of all three TG-rich lipoprotein particles and increased concentrations of Lp-A-II:B:C:D:E particles represent the main factors affecting the in vitro lipolytic rates of VLDL + IDL substrate in both the CRF patients before dialysis and patients on hemodialysis.
慢性肾衰竭(CRF)患者极低密度脂蛋白(VLDL)和中间密度脂蛋白(IDL)浓度升高被认为是血浆富含甘油三酯(TG)脂蛋白降解缺陷所致。本研究旨在确定与肾疾病患者和无症状对照者的VLDL与IDL混合底物脂解速率常数k1降低相关的脂蛋白异常情况。
从18例透析前患者(CRF-I)、8例血液透析患者(CRF-II)和10例无症状对照者中分离出VLDL + IDL。采用牛乳脂蛋白脂肪酶法并通过气相色谱法(GC)测定孵育前后的TG来测量VLDL + IDL的脂解速率常数(k1)。通过GC测定中性脂质,通过免疫电泳法测定载脂蛋白;通过免疫亲和色谱法测定包括Lp-B:C、Lp-B:C:E和Lp-A-II:B:C:D:E在内的载脂蛋白定义的富含TG的脂蛋白。
CRF-I组和CRF-II组患者的VLDL + IDL的k1值(分别为0.0341和0.0352 min-1)显著低于对照组(0.0515 min-1)(P < 0.001)。两组CRF患者中,以每毫克VLDL + IDL中100 mg TG标准化的载脂蛋白B、C-III和E以及富含TG的Lp-B:C、Lp-B:C:E和Lp-A-II:B:C:D:E颗粒的水平均显著高于对照组。所有三种富含TG的脂蛋白的游离胆固醇(FC)和酯化胆固醇(CE)百分含量均显著增加,而TG百分比降低。CRF-I组和CRF-II组合并患者组的k1值与FC(r = -0.81)和CE(r = -0.63)呈显著负相关(P < 0.001),与TG呈正相关(r = 0.72)。在脂蛋白颗粒中,只有Lp-A-II:B:C:D:E水平与k1值呈显著负相关(r = -0.47,P < 0.03)。
本研究表明,所有三种富含TG的脂蛋白颗粒的中性脂质组成异常以及Lp-A-II:B:C:D:E颗粒浓度升高是影响透析前CRF患者和血液透析患者体外VLDL + IDL底物脂解速率的主要因素。