糖基化磷脂酰肌醇磷脂酶D与动脉粥样硬化关系的研究

Study of the effect of glycosylphosphatidylinositol-specific phospholipase D on atherosclerosis

目的探讨糖基化磷脂酰肌醇特异性磷脂酶D（GPI—PLD）在动脉粥样硬化病理生理过程中的作用及其机制。方法分别收集102例冠心病患者和121例健康者外周血，测定其外周血GPI-PLD酶活性及其单个核细胞GPI—PLDmRNA表达。构建高表达GPI—PLD基因HUVEC细胞模型，并设立空白组和对照组，进行omLDL诱导，观察各组内皮细胞功能及生物学特性的改变。结果冠心病患者和健康者其外周血GPI—PLD酶活性分别为31．80±4．21和44．32±4．50，单个核细胞GPI—PI，DmRNA表达比值分别是0．92±0．16和1．53±0．14；冠心病患者组外周血GPI—PLD酶活性（t=21．31，P〈0．01）及其mRNA表达（t=30．36，P〈0．01），较健康者组分别减少28．2％和39．9％。ox-LDL诱导的各组细胞，高表达GPI-PLD细胞模型组细胞表面黏附单核细胞数、内皮素1、活性氧、丙二醛及凋亡率均低于空白组[29．59±1．40、3．51±0．45、（50．63±4．22）ng／L、0043±0．011、（3．32±0．44）nmol／L比41．39±2．15、10．57±1．12、（59．35±4．45）ng／L、0．052±0．011、（5．01±0．69）nmol／L3和对照组[42．68±2．45、9．92±1．03、（61．11±4．12）ng／L、0051±0．007、（4．89±0．71）nmol／L]，而一氧化氮含量高于空白组[（29．88±1．37μmol／L比（21．76±1．02）μmol／L]和对照组（23．43±0．85）μmol／L。结论GPI-PLD基因在冠心病患者中低表达，稳定高表达GPI—PLD有助于血管内皮细胞损伤的修复，有助于阻止动脉粥样硬化的发生和发展。

Objective To investigate the effect of glycosylphosphatidylinositol specific phospholipase D （GPI-PLD） on artherosclerosis. Methods The GPI-PLD activities and mononuclear cells GPI-PLD gene mRNA expression was detected in 102 patients with coronary artery disease and 121 healthy adult. The GPI-PLD highly expressing cell model was constructed and induced by ox-LDL, the HUVEC and HUVEC transfected with pcDNA3.1 （＋） as blank and control group, respectively. Before and after the induction, the change of cellular function and biological features was detected. Results The peripheral blood GPI-PLD activity of patients with coronary heart disease and normal control were 31.80 ± 4.21 and 44.32 ± 4.50, and the IA ratio of GPbPI.D mRNA expression of mononuclear cells were 0.92 ±0. 16 and 1. 53± 0.14, respectively. The activity of GPI PLD and mRNA expression in patients with coronary artery disease were decreased up to 28.2% （t= 21.31, P〈0.01） and 39.9% （t=30.36, P〈0.01） as compared with healthy control. The adhesion cells, ET-1, reactive oxygen, malondialdehyde （MDA） and the apoptosis rate of GPI-PLD overexpressing HUVEC were lower as compared with blank [29.59 ± 1.40, 3.51± 0.45, （50.63 ±4.22） ng/L, 0.043±0.011, （3.32±0.44） nmol/Lvs. 41.39vs2.15, 10.57±1.12, （59.35±4.45） ng/L, 0. 052±0. 011, （5. 01±0.69） nmol/L3, and as compared with control （42. 68±2.45, 9.92±1.03,（61.11±4.12） ng/L, 0. 051±0. 007, （4. 89±0.71） nmol/L] after inducing by ox-LDL; while the level of nitrogen noxidium （NO） was higher than blank [（29. 88± 1.37）μmol/L. vs. （21. 76±1.02）μmol/L. and control（23.43±0.85）μmol/L groups of GPI-PLD in patients with coronary artery disease are expression of GPI-PLD is beneficial to vascular endothelial occurrence and development of atherosclerosis. Conclusions The expression and activity lower than health people. Stable high ceil injury repairment and prevent the occurrence and development of atherosclerosis.