Specific alterations in plasma proteins during depressed,manic, and euthymic states of bipolar disorder

Bipolar disorder (BD) is a common psychiatric mood disorder affecting more than 1-2% of the general population of different European countries. Unfortunately, there is no objective laboratory-based test to aid BD diagnosis or monitor its progression, and little is known about the molecular basis of BD. Here, we performed a comparative proteomic study to identify differentially expressed plasma proteins in various BD mood states (depressed BD, manic BD, and euthymic BD) relative to healthy controls. A total of 10 euthymic BD, 20 depressed BD, 15 manic BD, and 20 demographically matched healthy control subjects were recruited. Seven high-abundance proteins were immunodepleted in plasma samples from the 4 experimental groups, which were then subjected to proteome-wide expression profiling by two-dimensional electrophoresis and matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight tandem mass spectrometry. Proteomic results were validated by immunoblotting and bioinformatically analyzed using MetaCore. From a total of 32 proteins identified with 1.5-fold changes in expression compared with healthy controls, 16 proteins were perturbed in BD independent of mood state, while 16 proteins were specifically associated with particular BD mood states. Two mood-independent differential proteins, apolipoprotein (Apo) A1 and Apo L1, suggest that BD pathophysiology may be associated with early perturbations in lipid metabolism. Moreover, down-regulation of one mood-dependent protein, carbonic anhydrase 1 (CA-1), suggests it may be involved in the pathophysiology of depressive episodes in BD. Thus, BD pathophysiology may be associated with early perturbations in lipid metabolism that are independent of mood state, while CA-1 may be involved in the pathophysiology of depressive episodes.     

不同人群载脂蛋白E基因频率分布特征

目的 :研究江苏地区汉族人群载脂蛋白E(ApoE)基因型及等位基因频率 ,并与国内外不同人群比较分布特征。方法 :聚合酶链反应 -限制性片段长度多态性 (PCR -RFLP)方法检测 16 8例江苏地区无血缘关系汉族人群ApoE基因型。计算各基因型及等位基因频率。结果 :江苏地区汉族人群载脂蛋白E各基因型频率分别为 :ε2 / 2 =0 .6 0 % ;ε2 / 3 =11.90 % ;ε2 / 4 =1.2 0 % ;ε3 / 4 =10 .70 % ;ε3 / 3 =75 .0 0 % ;ε4 / 4 =0 .6 0 % ;各等位基因频率分别为 :ε2 =7.14% ;ε3 =86 .31% ;ε4 =6 .5 5 %。频率分布在不同年龄、性别无显著差异。与其他地区中国人群频率分布相似。中国人群ε3 等位基因频率明显高于欧美人群 ,而ε4等位基因频率明显低于欧美人群。结论 :江苏地区汉族人群载脂蛋白E等位基因频率分布与其他地区中国人群频率分布相似 ,但与欧美人群有显著差异。     

老年高血脂患者Apo C检测的临床意义

目的探讨老年高血脂患者血清载脂蛋白CⅡ、CⅢ(Apo CⅡ、CⅢ)的变化及意义.方法免疫比浊法测定老年不同高血脂组血清Apo CⅡ、Apo C Ⅲ水平,并分析与其他指标的相关性.结果老年高血脂患者血清Tch、LDL水平各组间无差异(P＞0.05),且与TG浓度无明显相关; TG浓度与HDL水平呈负相关关系(r=0.435,P＜0.001),与Apo CⅡ、Apo CⅢ水平呈正相关关系(r=0.478,0.426,P＜0.001):老年高血脂患者血清Apo C Ⅱ、Apo CⅢ水平在男女性别间无显著性差异(P＞0.05).结论血清Apo CⅡ、Apo CⅢ水平与动脉粥样硬化危险因子TG呈正相关,提示其在老年人心血管疾病的发生中起一定的作用.     

载脂蛋白E基因多态性与脑梗死的相关性分析

目的　探讨载脂蛋白 E基因多态性与脑梗死的关系。方法　通过聚合酶链反应 -限制性片段长度多态性 (PCR- RFL P)分析结合 DNA直接银染技术检测 6 6例脑梗死 (CI)患者的载脂蛋白 E(Apo E)基因型 (其中家系中有明确脑梗死先证者的家族聚集性脑梗死 (FMACI)亚组 2 6例 ,家系中无脑卒中史的非家族聚集性脑梗死 (NF-MACI)亚组 4 0例 ) ,并与 90例健康对照组比较 ,同时检测血脂、脂蛋白 (a) [L P(a) ]及部分载脂蛋白。结果　脑梗死组ε3/4基因型频率明显高于对照组 (P<0 .0 1) ,ε3/3基因型频率明显低于对照组 (P<0 .0 1) ;两脑梗死亚组之间的ε3/4/ε3/3基因型频率虽有上升 /下降趋势 ,但未发现明显的统计学差异 ;FMACI组高密度脂蛋白 (HDL )水平明显低于 NFMACI组 (P<0 .0 5 )。结论　 Apo E基因多态性与脑梗死的发生有关 ,ε4等位基因是脑梗死的易感因子 ,ε3等位基因对脑梗死的发生有保护作用 ;Apo E基因多态性和 HDL水平双重作用于家族聚集性脑梗死的发生。     

2型糖尿病患者载脂蛋白E基因多态性的研究

目的：探讨中国人2型糖尿病患者载脂蛋白E（apoE)基因多态性及其与血脂和载脂蛋白水平的关系。方法：采用聚合酶链反应－限制性酶切片段长度多态性法，分别对74例2型糖尿病患者及191例血脂、血糖正常且无糖尿病史者的apoE基因型、空腹血脂及载脂蛋白AI、AⅡ、B100、CⅡ、CⅢ及E进行全面分析。结果：2型糖尿病患者的血清甘油三酯（TG）、总胆固醇（TC），低密度脂蛋白胆固醇（LDLC），非高密度脂蛋白胆固醇（nHDLC),载脂蛋白B100、CⅡ、CⅢ、E水平及TG／HDLC比值较对照组显著升高（P＜0．01）；血清高密度脂蛋白胆固醇（HDLC），apoE/apoCⅢ比值显著降低（P＜0．05）。2型糖尿病组与对照组apoE基因频率分布无显著性差异（P＞0．05）。携带ε2等位基因组血清TG／HDLC比值较E3／3基因型显著降低；而携带ε4等位基因组血清apoAⅡ水平较E3／3基因型及携带ε2等位基因组显著升高（P＜0．001）。结论：2型糖尿病患者apoE基因多态性与血TG／HDLC及apoAⅡ有一定关联。     

Variation of Apolipoprotein A-I in Cirrhosis and its Clinical Value

The serum apolipoprotein A- I (apo A-I) Concentrations in 39 patients with posthepatitis cirrhosis were reported to be 0.87±0.27 g/L lower than that of controls 1.15±0.14 g/L P<0.01. The, decrease of apo. A-I was correlated with the severityof impaired liver function. Apo A- I concentrations in serum correlated positively with decrease of serum albumin (r=0.503 P< 0.01) and negatively with serum bilirubin increase (r=- 0.508 P <0.01) . The data indicate that decreasing of apo A- I concentration may be regarded as one of the reliable indices reflecting the degree of liver function impairment.     

糖尿病中促动脉粥样硬化因素的探讨

我们对64例糖尿病患者和20名正常人的糖代谢、脂代谢、血小板和血管内皮细胞前列腺素代谢的水平进行了临床观察。发现糖尿病患者载脂蛋白B、低密度脂蛋白胆固醇、总脂固醇、甘油三酯和血栓素B_2的浓度均有不同程度的升高,而载脂蛋白A_1、高密度脂蛋白胆固醇和6-酮前列腺素F_(1α)的浓度则下降。同时糖代谢异常与脂代谢紊乱、糖代谢异常与前列腺素代谢物水平、以及脂代谢紊乱与前列腺素代谢物水平之间均无明显关系。推想糖尿病中促动脉粥样硬化的各种高危因素可能从不同的角度作用于血管壁,促进动脉粥样硬化的发生和发展。     

Apolipoprotein E4 enhances brain inflammation by modulation of the NF-κB signaling cascade

Apolipoprotein E4 (apoE4), the major genetic risk factor of Alzheimer's disease (AD), is associated with enhanced brain inflammation. Genome-wide gene expression profiling was employed to study the effects of apoE genotype on hippocampal gene expression in LPS-treated mice, transgenic for either apoE4 or the AD benign allele, apoE3. This revealed that the expression of inflammation-related genes following intracerebroventricular injection of LPS was significantly higher and more prolonged in apoE4 than in apoE3 transgenic mice. Clustering analysis revealed gene clusters which responded differently in apoE4 and apoE3 mice and were significantly enriched in NF-kappaB response elements. Direct measurement of NF-kappaB-regulated genes revealed that their extent of activation was greater in the apoE4 mice. Immunohistochemistry experiments revealed that microglial and NF-kappaB activation were more pronounced in apoE4 than in apoE3 mice. These findings suggest that the increased brain inflammation in apoE4 mice is related to disregulation of NF-kappaB signaling pathway.     

胆固醇代谢与阿尔茨海默病关系的研究进展

在阿尔茨海默病(AD)发病机制中,占主导地位是Aβ瀑流学说:由于淀粉样前体蛋白的代谢紊乱,产生了过量的Aβ42,后者迅速聚集形成寡聚物,启动了Aβ瀑流效应,造成了Aβ的沉积,形成老年斑.越来越多的实验表明,胆固醇在Aβ的产生和异常沉积过程具有重要调节作用,同时Aβ对胆固醇调节也有反馈作用,探讨两者的相互作用和影响有助于AD发病机制的阐明.而与胆固醇代谢密切相关的因素,如载脂蛋白E、调节胆固醇代谢的药物等也成为研究的热点.     

载脂蛋白A1、B基因多态性对非创伤性股骨头坏死发生的影响

目的:探讨载脂蛋白A1、B基因多态性对非刨伤性股骨头坏死(avascular necrosis of the femoral head,ANFH)发生的影响.方法:应用聚合酶链反应对中国北方汉族143例ANFH患者和92例正常人分别扩增含Apo AI基因启动子-75 bp和第一内舍子 83 bp及Apo B基因Eco RI、XbaI和3-VNTR的DNA片段,限制性内切酶酶切扩增产物,琼脂糖凝胶电泳分离基因多态性.结果:Apo A1基因启动子-75 bp处,ANFH患者中A/A基因型频率明显高于正常组(P＜0.01),而G/A基因型频率明显低于正常组(P＜0.01).Apo AI内舍子 83 bp位点,Apo B基因Eco RI、Xba I位点和3-VNTR区域ANFH患者组和正常组基因型及等位基因频率分布无统计学差异.结论:Apo A1基因启动子区域-75bp位点A/A型可能是非创伤性股骨头坏死易感基因之一,但未能发现Apo A1第一内舍子 83 bp位点及Apo B基因Eco RI、XbaI和3-VNTR位点多态性与非创伤性股骨头坏死发生有明显的关系.