Alterations of Lipid Metabolism in Response to Nerve Growth Factor

Abstract: In response to nerve growth factor (NGF), clonal pheochromocytoma cells flatten and extend neurites capable of making functional synapses. Although no significant changes in overall phospholipid composition occur in the presence of NGF, there is increased incorporation of ³²PO₄ into phosphatidylinositol and phosphatidic acid within 10 min after the addition of NGF. NGF stimulates the incorporation of ³²PO₄ into other lipids, such as phosphatidylcholine, to a lesser extent. The kinetics of the NGF-induced phosphatidylinositol responses are different when the cells are in suspension from when they are attached to culture dishes. These changes in phospholipid metabolism are discussed with respect to their role in NGF-induced nerve differentiation.     

代谢酶乙酰化修饰对新陈代谢的调控

蛋白质的赖氨酸乙酰化修饰可以定义为在蛋白质的赖氨酸残基上添加或移除一个乙酰基团,这个过程是由乙酰化酶和脱乙酰酶调控的.真核生物细胞核内组蛋白和转录因子的可逆乙酰化修饰对基因表达调控的机制早已研究得比较清楚.1996年以来,一些独立的研究也陆续发现,参与到其他生命活动中的蛋白质存在着乙酰化修饰情况,表明乙酰化可能在生命活动中发挥着广泛的调节作用.然而直到2009年,高通量的蛋白质质谱分析技术才使得在蛋白质组水平上研究乙酰化修饰成为可能,并发现蛋白质乙酰化普遍存在.学者们发现,乙酰化修饰是一个在细胞核或细胞质的亚细胞器内广泛存在的翻译后修饰调控机制,可能参与了染色体重塑、细胞周期调控、细胞骨架的大分子运输、新陈代谢等多种生命活动.本文详细总结代谢酶的乙酰化修饰对新陈代谢调控的关键作用,并说明代谢酶的乙酰化修饰是一个从原核生物到真核生物进化上高度保守的调控机制.     

Presence of Platelet-Activating Factor and Its Receptor in Baboon (Papio spp) Spermatozoa

Platelet-activating factor [1-O-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine; PAF] is a novel potent signaling phospholipid which has unique pleiotropic biological properties in addition to platelet activation. PAF has been detected in the spermatozoa in several species. The concentration of PAF is inversely related to human spermatozoal quality. PAF is present in squirrel monkey (a seasonal breeder) spermatozoa and is significantly higher during the breeding season. PAFs mechanism of action is a receptor-mediated event. There is no report on the presence of PAF or the PAF-receptor in nonhuman Old World primate spermatozoa. Therefore, the primary objective of this study was to determine if PAF is present in the spermatozoa from baboons, which are year-round breeders. A secondary objective was to determine the presence and localization of the PAF-receptor in spermatozoa. We extracted endogenous lipids from mature hybrid baboon (Papio spp) epididymal spermatozoa and assayed them for the presence of PAF by [ ¹²⁵ I]-radioimmunoassay. We also exposed baboon spermatozoa to PAF-receptor antibody followed by FITC-conjugated antibody. PAF was in all samples assayed (mean: 2.29 (±0.63) pmol/10 ⁶ spermatozoa). Baboon spermatozoa possess PAF-receptors most prevalently along the neck and midpiece regions. The data demonstrates that PAF and its receptor are present in baboon spermatozoa. Additional studies will elucidate the role of PAF in spermatozoal function.     

Inhibition of Human Platelet Aggregation by Amides and Ester of Salicylic Acid with Platelet-Activating Factor Analogs

The influence of acetyl salicylic acid (ASA) derivatives with platelet-activating factor (PAF) lipid analogs on PAF-induced human platelet aggregation has been studied. It was found that the ASA amide with an ethanolamine plasmalogen PAF analog (1-0-alk-1"-enyl-2-acetyl-sn-glycero-3-phospho-(N-2"-acetoxybenzoyl)ethanolamine) and the ASA ester with a choline plasmalogen PAF analog (1-0-alk-1"-enyl-2-(2"-acetoxybenzoyl)-sn-glycero-3-phosphocholine) at concentrations of 10^–7-10^–6 M effectively inhibit PAF-induced aggregation of human platelets. In contrast to these compounds, the ASA amide with an alkyl PAF analog (1-0-alkyl-2-acetyl-sn-glycero-3-phospho-(N-2"-acetoxybenzoyl)ethanolamine) did not inhibit PAF-induced platelet aggregation. As possible mechanisms of action of the studied compounds, the blockade of PAF-receptor and cyclooxygenase inhibition are proposed.     

内质网应激与肝细胞脂类代谢

肝细胞担负大量的代谢功能,包括脂肪酸的合成与类固醇的代谢。内质网应激反应（ERstressresponse）作为内质网中特殊的机制用以保证内质网内部的稳态和功能正常。有研究指出内质网应激诱导的信号通路及其通路上的关键蛋白参与肝细胞的脂类代谢过程。本文主要讨论内质网应激反应影响肝细胞脂类代谢的机制,以及内质网应激与脂类代谢紊乱疾病的相关性。     

n-3PUFA调节脂代谢机制的研究进展

日粮中的n-3PUFA具有多种作用,除了调节质膜组成和影响细胞信号之外,同时还涉及多 种与脂代谢有关酶与蛋白的基因表达,如:PPARα、SREBPs、LXR等,通过它们来影响靶基因(如: ACO-A、FAS等)的表达,从而起到调控脂肪沉积的作用。     

氟西汀联合利培酮对精神分裂症患者血脂代谢、认知中记忆维度和血清神经营养因子的影响

摘要 目的：探讨氟西汀联合利培酮对精神分裂症患者血脂代谢、认知中记忆维度和血清神经营养因子的影响。方法：本次研究纳入病例110例,选取自2018年3月~2020年8月期间我院接收的精神分裂症患者。根据就诊奇偶顺序将患者分为对照组和研究组,各55例。对照组给予利培酮治疗,研究组给予氟西汀联合利培酮治疗,均治疗12周。对比两组治疗12周后的疗效,对比两组治疗前、治疗12周后的血脂代谢、认知中记忆维度、血清神经营养因子水平及阳性和阴性症状量表（PANSS）评分,记录两组不良反应发生率。结果：研究组的临床总有效率优于对照组（P<0.05）。两组治疗12周后总胆固醇（TC）、三酰甘油（TG）、低密度脂蛋白（LDL-C）较治疗前升高,高密度脂蛋白（HDL-C）降低较治疗前（P<0.05）。两组治疗12周后简易视觉空间记忆测验-修订版（BVMT-R）、韦克斯勒空间广度测验-Ⅲ（WMS-Ⅲ）、霍普金斯词语学习测验-修订版（HVLT-R）评分升高,且研究组高于对照组（P<0.05）。两组治疗12周后血清脑源性神经营养因子（BDNF）、胶质源性神经营养因子（GDNF）升高,且研究组高于对照组（P<0.05）。两组治疗12周后阳性症状评分、一般病理评分、总分、阴性症状评分降低,且研究组较对照组低（P<0.05）。两组不良反应总发生率比较无差异（P>0.05）。结论：氟西汀联合利培酮治疗精神分裂症患者,可有效改善认知功能,改善血清神经营养因子水平,且不加重血脂紊乱程度,不增加不良反应发生率,安全有效。     

Production and Metabolism of Platelet-Activating Factor in the Normal and Ischemic Fetal Rat Brain

Abstract: Production and metabolism of platelet-activating factor (PAF) in the fetal rat brain under normal and under ischemic stress conditions were examined. Endogenous PAF levels, determined by a bioassay using PAF-stimulated platelet release of [³H]serotonin, averaged 2.32 ± 2.14 pg/mg in control brains and was reduced to 1.10 ± 1.06 pg/mg after 20 min of maternal-fetal blood flow occlusion. [³H]PAF administered intracranially into the fetuses in utero was removed in a biphasic, time-dependent manner: a rapid component with an estimated elimination rate constant of 0.067 min^?1 and t_1/2 of 10 min and a slower component with an elimination rate of 0.017 min^?1 and t_1/2 of 41 min. In fetal brains subjected to ischemia a delayed elimination of [³H]PAF was noticed in the slow component (t_1/2 = 59 min), indicating a possible difference between the clearance of exogenous and endogenous PAF. The disappearance of [³H]PAF was accompanied by an increase in the radioactivity associated with lyso-PAF that reached a plateau after 2.5 min, possibly indicating the degradation of the fast component. A steady increase in the alkyl-acyl-glycerophosphorylcholine radioactivity commenced after 5 min and continued up to 30 min. The endogenous production of PAF and the rapid degradation due to maternal-fetal blood flow occlusion indicate an additional target for therapeutic intervention in the pathology of intrauterine ischemia. Addition of the calcium ionophore A23187 stimulated in vitro formation of PAF and lyso-PAF from [³H]-choline-labeled fetal brain phospholipids, suggesting that intracellular calcium may play a major stimulatory role in PAF production. Degradation of polyphosphoinositides by a phospholipase C may constitute a major target for PAF generated either by decapitation or after blood flow occlusion, as evident from the protective effect of the in vivo administered BN52021 PAF antagonist.     

n-3 PUFAs对脂质代谢和炎症-免疫的调节机制

n-3多不饱和脂肪酸(n-3 PUFAs)是一种重要的营养物质,其具有多种生理作用,可作为一种基因表达的调控物直接和独立地调控基因表达,并广泛地影响着动物体内有关代谢及生理病理现象。主要从调节机制方面对n-3 PUFAs对机体脂质代谢和炎症-免疫的影响进行综述。     

不同劳动者类型脂代谢相关表型的差异分析

目的:比较体力劳动者与脑力劳动者在脂代谢相关表型方面是否有差异。方法:随机抽取泰州市30-75岁个体127例(体力劳动者63例,脑力劳动者64例),进行体力活动日记、身高、体重、腰围、臀围、收缩压、舒张压体格指标测量。取静脉血测量血清空腹血糖(Glu)、总胆固醇(TC)和甘油三酯(TG);使用酶联免疫吸附法测量血清中脂代谢生物标志物低密度脂蛋白受体(LDLR)、载脂蛋白A5(Apo A5)、载脂蛋白B100(Apo B100)、微粒体甘油三酯转运蛋白(MTTP)。采用T检验和卡方检验统计方法比较体力劳动者与脑力劳动者脂代谢相关表型是否有统计学差异。结果:脑力劳动者组的体力活动能量消耗显著低于体力劳动者组(P<0.05),且随着能量消耗等级递增而比例递减(P<0.05)。脑力劳动者组BMI水平显著高于体力劳动者组(P<0.05)。另外,脑力劳动者组在LDLR、Apo A5、Apo B100分子水平都显著低于体力劳动者组(P<0.05)。结论:不同劳动类型影响脂代谢相关表型水平的高低。     

卡维地洛对轻中度高血压患者血脂代谢的影响

目的:探讨卡维地洛对轻中度高血压患者血脂代谢的影响。方法:随机选取我院2012年1月~2015年1月收治的80例轻中度高血压患者为研究对象,将其分为观察组和对照组,观察组采用卡维地洛对其治疗,对照组给予美托洛尔治疗,比较两组的治疗效果、治疗前后血压、心率及血脂水平的变化。结果:观察组患者的治疗总有效率为90%,而对照组患者的治疗总有效率为72.5%,显著低于观察组,差异具有显著性(P0.05)。治疗后,两组患者的收缩压、舒张压和心率均较治疗前均降低,差异具有显著性(P0.05),但两组之间收缩压、舒张压相比差异不具有统计学意义,而观察组患者的心率显著高于对照组(P0.05)。治疗后,观察组总胆固醇(TC)、甘油三酯(TG)及低密度脂蛋白(LDL-C)水平均较治疗前显著降低,且低于对照组,而高密度脂蛋白(HDL-C)水平显著高于治疗前,且高于对照组,差异均具有统计学意义(P0.05)。结论:卡维地洛较美托洛尔可更有效治疗轻中度高血压患者,同时改善患者的血脂水平,且对患者心率的影响较小。     

基于脂代谢特点建立豚鼠动脉粥样硬化模型优势的研究进展

动脉粥样硬化（AS）在全球的发病率逐年升高,有关AS 的研究也越来越深入,合适的动物模型是研究动脉粥样硬化机制和 药物研发的关键环节。在众多动物模型中豚鼠作为动脉粥样硬化的研究对象存在众多优势,主要体现在血浆脂蛋白的构成比例、 胆固醇的转运形式、肝脏中胆固醇的存在形式与比例、对外源性胆固醇的敏感性、胆固醇与脂蛋白代谢过程中关键酶的活性变化 等方面。本综述基于脂代谢特点,对比分析这几个方面内容来阐述豚鼠作为动脉粥样硬化动物模型的优势。     

糖耐康含药血清对高糖状态下大鼠肝细胞糖脂代谢的影响

摘要目的：研究糖耐康含药血清对高糖状态下大鼠肝细胞糖脂代谢的影响。方法：通过培养大鼠肝细胞,在高糖诱导肝细胞胰岛素抵抗状态下,给予高、中、低剂量的糖耐康含药血清共培养24h后,观察肝细胞增殖情况,用葡萄糖氧化酶法检测细胞的葡萄糖消耗量,培养基和肝细胞内TG含量,肝细胞糖原含量。结果：与正常组比较,高糖刺激下,肝细胞增殖显著受到抑制（P〈O．叭）、葡萄糖消耗量和糖原含量减少（P〈0．01）,TG含量增加（P〈O．01）;与高糖组比较,吡格列酮组与TNK各剂量上述情况有不用程度的改善。作用效果类似。结论：糖耐康含药血清具有改善高糖环境下肝脏糖脂代谢紊乱的作用,可能与增加肝细胞胰岛素敏感性改善IR有关。     

法尼酯X受体在脂质代谢过程中的调控作用

法尼酯X受体(Farnesoid X Receptor,FXR)属于配体依赖的核转录因子,可被内源性配体胆汁酸激活,通过调节胆汁酸、胆固醇、脂蛋白及脂肪酸代谢维持血浆中脂质的稳态,从而达到调节脂质代谢的目的。最近研究发现FXR在脉管系统中也有表达活性,开辟了FXR调节脂质代谢的新途径。随着新配体及靶基因的发现,研究FXR的作用机制以及寻找对脂质代谢具有调控作用的FXR的配体,对于脂代谢异常和动脉粥样硬化的防治具有重要意义。本文综述了该领域的最新进展。     

Free Radicals Scavengers Attenuate Platelet-Activating Factor (PAF)-And Endotoxin-Induced Intestinal Myoelectric Disturbances in Rats

Pretreatment with radical scavengers significantly reduced the intestinal myoelectric disturbances following either E. coli endotoxin or platelet-activating factor (PAF) injection in the rat indicating that free radicals might be involved in the intestinal motor alterations observed in endotoxin shock and that PAF acts partially via free radical production. Moreover, dimethylsulfoxide (DMSO) was found to be more effective in inhibiting the endoxotin-induced intestinal motor alterations, than superoxide dismutase (SOD) and allopurinol. BN 52021, a specific PAF antagonist, was able to reduce the effects of endotoxin on intestinal motility, However, when BN 52021 was combined with free radical scavengers, no additive effect was observed. It is concluded that free radicals involved in endotoxin-induced intestinal motility alterations are at least in part produced in response to PAF.     

镁补充对2 型糖尿病大鼠糖脂代谢的影响

目的:研究镁补充对2型糖尿病大鼠糖脂代谢的影响。方法:将用高脂饮食联合链脲佐菌素(STZ)方法诱发的2型糖尿病大鼠随机分为四个组,糖尿病对照组喂饲高脂饲料,高、中、低剂量组在高脂饲料中分别加入2000、1000、200 mg/kg的镁(以镁离子计)。自由饮食喂养四周,处死动物。用放射免疫法测血清胰岛素(Ins)水平、用葡萄糖氧化酶法测空腹血浆葡萄糖(fasting plasmaglucose,FPG),并计算胰岛素敏感指数(insulin sensitivity index,ISI)。比色法检测糖化血红蛋白(glycosylated hemoglobin,HbA1c)。用全自动生化分析仪测高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDLC)、甘油三酯(triglyceride,TG)、总胆固醇(total cholesterol,TC)。结果:高剂量组的空腹血糖、空腹血清、糖化血红蛋白、甘油三酯、总胆固醇水平均较糖尿病对照组显著性降低(P<0.05),而高密度脂蛋白胆固醇、胰岛素敏感指数较糖尿病对照组显著性升高(P<0.05)。结论:镁补充可以提高2型糖尿病大鼠胰岛素敏感性,改善糖尿病大鼠的糖脂代谢情况。     

肌肉生长抑制素对脂肪细胞生长发育和脂代谢的调控

肌肉生长抑制素(MSTN)对骨骼肌生长的抑制作用已得到证实,但其调控脂肪组织的作用还不是十分清楚。本文综述了MSTN调控脂肪细胞生长发育和脂代谢的相关机制和可能研究趋势。     

Activities of Enzymes Involved in the Metabolism of Platelet-Activating Factor in Neural Cell Cultures During Proliferation and Differentiation

Platelet-Activating Factor (PAF) is a potent lipid mediator involved in physiological and pathological events in the nervous tissue where it can be synthesized by two distinct pathways. The last reaction of the de novo pathway utilizes CDPcholine and alkylacetylglycerol and is catalyzed by a specific phosphocholinetransferase (PAF-PCT) whereas the remodelling pathway ends with the reaction catalyzed by lyso-PAF acetyltransferase (lyso-PAF AcT) utilizing lyso-PAF, a product of phospholipase A₂ activity, and acetyl-CoA. The levels of PAF in the nervous tissue are also regulated by PAF acetylhydrolase that inactivates this mediator. We have studied the activities of these enzymes during cell proliferation and differentiation in two experimental models: 1) neuronal and glial primary cell cultures from chick embryo and 2) LA-N-1 neuroblastoma cells induced to differentiate by retinoic acid (RA). In undifferentiated neuronal cells from 8-days chick embryos the activity of PAF-PCT was much higher than that of lyso-PAF AcT but it decreased during the period of cellular proliferation up to the arrest of mitosis (day 1–3). During this period no significant changes of lyso-PAF AcT activity was observed. Both enzyme activities increased during the period of neuronal maturation and the formation of cellular contacts and synaptic-like junctions. The activity of PAF acetylhydrolase was unchanged during the development of the neuronal cultures. PAF-PCT activity did not change during the development of chick embryo glial cultures but lyso-PAF AcT activity increased up to the 12th day. RA treatment of LA-N-1 cell culture in proliferation decreased PAF-PCT activity and had no significant effect on lyso-PAF AcT and PAF acetylhydrolase indicating that the synthesis of PAF by the enzyme catalyzing the last step of the de novo pathway is inhibited when the LA-N-1 cells are induced to differentiate. These data suggest that: 1) in chick embryo primary cultures, both pathways are potentially able to contribute to PAF synthesis during development of neuronal cells particularly when they form synaptic-like junctions whereas, during development of glial cells, only the remodelling pathway might be particularly active on synthesizing PAF; 2) in LA-N-1 neuroblastoma cells PAF-synthesizing enzymes coexist and, when cells start to differentiate the contribution of the de novo pathway to PAF biosynthesis might be reduced.     

脂类代谢异常在恶性肿瘤中的研究进展

过度增殖是恶性肿瘤细胞的生物学特性,为满足不断增殖及生存的需要,肿瘤细胞需重新编码代谢通路。近年来的研究认为,脂类代谢异常是肿瘤细胞的重要特征之一,肿瘤细胞中异常的脂类代谢不仅与代谢酶有关,还与代谢通路以及其他相关信号传导有关。本文通过回顾既往研究报道的肿瘤细胞脂类代谢的变化,探讨脂类代谢的异常调节与肿瘤发生的可能机制,为肿瘤的预防及治疗提供新思路。     

高脂饮食对小鼠脂质代谢和leptin基因表达水平的影响

目的建立高脂饮食诱导小鼠肥胖模型,分析高脂饲料对小鼠脂质代谢和leptin基因表达水平的影响。方法用高脂饲料饲喂小鼠,每周定时称重和断尾采血一次,分别测定血清中血糖、胆固醇、甘油三酯、胰岛素和leptin的浓度;5周后,分离、称重小鼠体脂并提取腹部脂肪组织RNA,半定量RT-PCR分析leptin基因表达水平。结果从第2周开始,实验组小鼠体重明显高于对照组小鼠,4周后,体重差异显著（P〈0．05）;血清中血糖、胆固醇、甘油三酯、胰岛素和leptin的含量随体重增加明显增高,4周后,差异显著（P〈0．05）;实验组体脂含量明显高于对照组（P〈0．05）,半定量RT-PCR分析表明,肥胖小鼠脂肪组织leptin基因表达水平高于对照组（P〈0．05）。结论高脂饮食诱导可建立小鼠肥胖模型,并能够引起高胰岛素和高leptin血症,为进一步研究肥胖的发病机制奠定基础。