摘要
目的:脂蛋白相关磷脂A2(Lipoprotein-associated Phospholipase A2,LP-PLA2)又称为血小板活化因子乙酰水化酶,是一类能够在磷脂甘油部分的Sn-2位点选择性断裂酯键的酶,在生物界中分布广泛,尤其在哺乳动物,爬行动物,节肢动物的细胞、组织和体液中可分离出LP-PLA2。其来源包括:胰腺、胃、肠、脾、心、肝、肺、脑、软骨细胞、血管平滑肌细胞、多形核白细胞、巨噬细胞、红细胞、血小板、胰液、炎症性渗出液、腹水和精浆。人血浆LP-PLA2主要是由成熟的巨噬细胞、T淋巴细胞、单核细胞、和肥大细胞分泌生成的具有甘油磷脂分解活性的酶类家族。由其介导产生的脂质介质如前列腺素类物质,白三烯、溶血磷脂、血小板激活因子等具有在多种生理和病理条件下的磷脂转运、膜修复、胞外水解及神经元转移因子的释放等功能,因而,这类酶及其介导产物近来引起了人们的极大关注。
LP-PLA2的生理功能包括改造磷脂结构,促进机体坏死组织自体消失,参与肺泡表面活性物质代谢等。在磷脂的分解、消化、脱酰基/再酰化途径及平衡细胞磷脂池过程中扮演着重要角色。通过催化细胞膜的磷脂酰胆碱、磷脂酰乙醇胺、磷脂酰丝氨酸的sn-2位水解,产生以花生四烯酸为主的游离脂肪酸及溶血磷脂。炎症发生时,LP-PLA2活性升高,通过激活环氧化酶、脂氧化酶,进一步产生大量的廿碳烷酸类物质,如前列腺素、血栓素、白三烯及血小板活化因子等促炎细胞因子。这些活性物质通过各自的作用途径,继续诱导生成更多的炎性因子,形成级联瀑布效应,促进炎症的发展。因此,LP-PLA2将损伤因素、炎症细胞、脂类递质、细胞因子等细胞有形成分和可溶分子物质联系起来,成为该体系极其关键的活性酶。
最近流行病学和临床前瞻性研究均发现,发生冠心病事件者与对照组相比LP-PLA2质量或活性显著升高,因此认为血浆LP-PLA2质量或活性升高是心血管危险事件的独立危险因子。LP-PLA2水解氧化卵磷脂生成的溶血卵磷脂和氧化型游离脂肪酸是促炎介质,能刺激粘附因子和细胞因子的产生,从而促进单核细胞由管腔向内膜聚集。单核细胞在内膜聚集后衍生为巨噬细胞,巨噬细胞吞噬氧化型LDL变成泡沫细胞。泡沫细胞聚集成动脉粥样硬化性斑块,脆弱斑块的破裂,易导致血栓形成和心血管事件的发生。因此表现出很强的促动脉粥样硬化形成的作用,临床及实验室的研究结果均证实了这一点。
本研究通过检测糖尿病患者血浆中脂蛋白相关磷脂酶A2酶活性水平,探讨我国汉族2型糖尿病患者中脂蛋白相关磷脂酶A2的分布特征及影响其活性的相关因素。
方法:采用病例-对照研究,共纳入中国汉族2型糖尿病230例,根据颈部血管超声,动脉粥样斑块的结果,分为有动脉粥样硬化组(125例),无动脉粥样硬化组(105例);测定所有入组患者的身高、体重,计算体重指数;测定肝生化、肾功、血脂等常规生化指标;并留取血标本,采用免疫组化双抗体夹心ELISA的方法测定血浆中LP-PLA2的活性,用T检验的统计学方法处理数据,分析两组之间LP-PLA2酶活性的分布特征,同时进一步分析脂代谢紊乱、年龄、性别、肥胖、女性绝经、男性吸烟等因素对该酶活性分布的影响。
结果:脂蛋白相关磷脂酶A2活性在我国2型糖尿病患者中:有动脉粥样硬化组高于无动脉粥样硬化组;男性高于女性;绝经后女性组高于未绝经女性;肥胖患者高于非肥胖患者;低高密度脂蛋白者高于正常高密度脂蛋白者。高低密度脂蛋白者与正常低密度脂蛋白者之间未见统计学差异,满60周岁者与未满60周岁者之间未见统计学差异,男性吸烟与不吸烟者之间未见统计学差异。
结论:中国汉族2型糖尿病患者中,大血管病变有动脉粥样硬化组患者,血浆Lp-PLA2活性高,性别、肥胖、女性绝经及脂代谢紊乱尤其是低高密度脂蛋白血症,是影响2型糖尿病患者血浆Lp-PLA2活性的相关因素。
Objective:Lipoprotein - associated Phospholipase A2,(LP-PLA2),Also known as platelet-activating factor acetylhydrolase water activity, which is a class of phospholipid glycerol in the part of the Sn - 2 fracture sites ester selective enzyme. LP-PLA2 widely distributed in the biological, especially in mammals, reptiles, and arthropods cells, tissues and fluids can be separated.Its sources include:the pancreas, stomach, heart, bowel, spleen, liver, lungs and brain, cartilage cells and vascular smooth muscle cell nucleation, white and macrophages, red, platelets, pancreatic juice, inflammatory exudate, ascites and seminal plasma. LP-PLA2 in human plasma mainly composed of mature macrophages, T lymphocytes, mono- cytes, and mast cell secretion with glycerol phospholipids generated activity of enzymes break down the family. The production by its mediated the lipid medium such as prostanoid material, leukotrienes, were lysophospholipids platelet activate factor and so on. Which with the function of phospholipids transhipment, film repair, extracellular hydrolysis and neurons release of transfer factor and so on in many physiological and pathological conditions. Thus, this kind of enzymes and mediated product recently attracted great attention.
LP-PLA2 physiological functions including phospholipids structure, to promote the necrotic tissue autologous disappear. Participate in alveolar surface active substances metabolism, etc. In the decomposition, digestion, phosphatide acyl off or then acylation and balanced cell phospholipids pool processplay an important role. produced by arachidonic acid primarily free fatty acid and were lysophospholipids. Inflammation occurs, LP-PLA2 activity, through the activation ring oxidase, lipoxygenase, further produce large amounts of 20 carbon silane acid material, such as prostaglandins, thrombosis, and platelet activation leukotriene proinflammatory cytokines factor etc. These substances through their respective function approach, continue to induce more proinflammatory cytokines, forming a cascade falls, promote the development of effect of inflammation. Therefore, LP-PLA2 will damage factor, inflammatory cells, lipid neurotransmitter, cytokines cells visible part and soluble molecules, become the system key active.
Recent epidemiological and clinical prospective studies have found that Occurrence of coronary heart disease events compared with the control group or the quality of LP-PLA2 activity was significantly increased, so that the quality of plasma,or LP-PLA2 activity increased the risk of cardiovascular events is an independent risk factor.LP-PLA2 hydrolysis oxidation lecithin generated hemolysis lecithin and oxidation type free fatty acid is medium, can stimulate proinflammatory cytokines factor and adhesion, thus promote mononuclear cells lining by lumen to gather. After endometrium mononuclear cells in gathered to macrophage derived and macrophage cell oxidation type LDL into foam cells. Foam cell aggregation of atherosclerotic plaque, vulnerable plaques of rupture, easy cause thrombosis and cardioascular eents. Therefore showed a strong urge the role of atherosclerosis, clinical and laboratory findings confirm it.
This research through the detection of diabetes plasma lipoprotein related phospholipid A2 enzyme activity level in type 2 diabetes patients lipoprotein related phospholipid A2 distribution and influencing factors.
Materials and methods: Using case-control study, A Chinese han nationality 230 cases of type 2 diabetes. Vascular ultrasound according to the neck, the result of atherosclerotic plaque atheromatous plaque, Divided into atherosclerosis group (125cases), non-atherosclerotic group (105cases), Determination of all patients into the height, weight, calculated body mass index.Determination of liver biochemistry, renal function, blood lipids and other biochemical parameters of conventional. Collecting blood samples, using immunohistochemical double-antibody sandwich ELISA method in the determination of plasma LP-PLA2 activity, use t-test etc statistical methods processing data, analysis between two groups of enzyme LP-PLA2 activity distribution characteristics. And further analysis of lipid meta- bolism disorders, age, gender, obesity, postmenopausal, masculine smoking to this enzyme activity distributed influence.
Results:LP-PLA2 activity in our country type 2 diabetics: Atheros- clerosis group to be higher than without atherosclerosis group. The male is higher than the female. After the menopause, the feminine group is not higher than the menopause female. The obese patient is higher than the non-obese patient; Low clearance high density lipoprotein is higher than the high density lipoprotein normal person. Between hing clearance low density lipoprotein and the low density lipoprotein normal person not statistically significant differences . Between full 60 years old and under 60 years old not statistically significant differences .Men between smoking and non-smokers not statistically significant differences.
Conclusion:Chinese of the Han nationality patients with type 2 diabetes, the trunk pathological change, has atherosclerosis group, the blood plasma Lp-PLA2 activeness is high, Sex, obese and fat metabolic disorder particularly low high density lipoprotein, that affect patients with type 2 diabetes plasma Lp-PLA2 activity in the relevant factors.
引文
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