血糖波动加速载脂蛋白-E缺乏大鼠的动脉粥样硬化形成

本研究（Biochem Biophys Res Commun．2007 Jul 6；358（3）：679—85．Epub 2007 May4．）的目的是探讨血糖波动对动脉粥样硬化形成的影响。给载脂蛋白-E缺陷的大鼠每日两次喂养麦芽糖，造成餐后血糖反复波动，

2型糖尿病患者脂蛋白酯酶、血管紧张素转换酶及载脂蛋白-E基因多态性与冠心病的关系

目的 探讨 2型糖尿病患者脂蛋白酯酶 (LpL)、血管紧张素转换酶 (ACE)及载脂蛋白 E(ApoE)基因与冠心病的关系。方法 采用聚合酶链反应 限制性片段长度多态性 (PCR PFLP)、聚合酶链反应 (PCR)和聚合酶链反应 等位基因特异性寡核苷酸 (PCR ASO)探针杂交技术分别检测 2型糖尿病并冠心病组及对照组LpL、ACE、ApoE基因型。结果 ① 2型糖尿病并冠心病组LpL/P P 及P 频率分别为 18.2 %和 4 2 .9% ,高于对照组 (9.5 %和 32 .5 % ) ,但差异无统计学意义 (P >0 .0 5 )。LpL/HindⅢ多态性频率分布两组间无明显差异 (P >0 .0 5 )。② 2型糖尿病组ACE/DD及D频率分别为 33.8%和 5 7.1% ,明显高于对照组(12 .7%和 36 .5 % ) (P <0 .0 1)。③ 2型糖尿病并冠心病组ε 3/ 3和ε 4 / 3频率分别为 5 4 .8%和 31.2 % ,分别明显低于 (ε 3/ 3)和高于 (ε 4 / 3)对照组 (76 .19%和 11.11% ) (均为P <0 .0 1)。ε 4等位基因频率为 2 0 .8% ,明显高于对照组 (9.5 2 % ) (P =0 .0 1)。结论 LpL/ p 、ACE/D及ApoE/ε 4等位基因增高 2型糖尿病并发冠心病患者的遗传易感性。

中国人载脂蛋白E基因多态性与2型糖尿病合并冠心病关系的Meta分析

目的：本研究利用Meta分析的方法，综合评价中国人载脂蛋白E基因多态性与2型糖尿病合并冠心病的相关性。方法计算机及手工检索2014年12月以前中外有关中国汉族人群载脂蛋白E基因多态性与2型糖尿病合并冠心病关系的病例-对照研究。在评价纳入研究质量、提取有效数据后，采用RevMan 5.0软件进行Meta分析。结果共纳入5个病例对照研究，包括2型糖尿病并冠心病组646例，2型糖尿病无冠心病组752例。Meta分析结果显示：文献无明显发表偏倚。携带载脂蛋白Eε3/3基因型的人群2型糖尿病并冠心病的发病风险降低（ OR=0.51，95%CI：0.37~0.71），ε3/4基因型发病风险增高（OR=2.20，95%CI：1.52~3.20）；ε4等位基因发病风险增高（OR=2.07，95%CI：1.49~2.87）。结论中国汉族人群载脂蛋白Eε3/3基因型、ε3/4基因型、ε4等位基因多态性可能与2型糖尿病合并冠心病的发病有关。

The Effects of Apolipoprotein E Polymorphism on Serum Lipids, Lipoproteins and Apolipoproteins Variation

Objective: To study the effects of Apolipoprotein E (ApoE) polymorphism onserum levels of lipids, lipoproteins and apolipoproteins. Methods: Fragments of ApoE gene forthex-on containing codon 112 and 158 polymorphic locus were amplified by PCR, and then digested untilCfo I endonuclease. Genotypes and alleles frequencies of 168 healthy persons in Jiangsu area werecalculated. The effects of ApoE genotypes and alleles on serum lipids, lipoproteins andapolipoproteins variation were analyzed. Results: The effects of ApoE alleles on total cholesterol(TC), law density lipoprotein-cholesterol (LDL-C), ApoB was: along a decreasing gradientε_4>ε_3>ε_2. The effect of ε_4 allele was to increase serum levels of TC, LDL-C and ApoB, andthe ε_2 allele had an effect opposite to that of ε_4 allele. Conclusion: ApoE polymorphism is anindependent genetic factor on individual serum levels of lipids and apolipoproteins.

载脂蛋白E基因多态性与老年期抑郁症的关联性

目的 研究载脂蛋白E基因（apolipoprotein E gene,APOE）多态性与老年期抑郁症（geriatricdepression,GD）的关联,并探讨APOE基因型与患者抑郁症状、血脂水平及认知功能之间的关系.方法 采用单核苷酸多态性（single nucleotide polymorphism,SNP）位点检测技术检测120例GD患者及120例健康对照者APOE的rs7412及rs429358两多态性位点,分出各基因型;分析两组各基因型及等位基因频率差异;分析病例组APOE多态性与患者临床及人口学资料间的关系;采用Logistic多元回归分析各一般资料、临床资料对GD认知功能的影响.结果 两组基因型及各等位基因频率均差异无统计学意义（均P＞0.05）;携带ε4基因型的患者简易智能量表总分低于非携带者[（22.38±2.22）分,（25.28±2.28）分,t=3.091,P＜0.01],而血脂水平TC（t=2.225,P＜0.05）、LDL（t=2.728,P＜0.01）高于非携带者;携带e4患者典型临床表现为阻滞（载荷0.695）和认知障碍（载荷0.902）,而非携带者突出表现在焦虑躯体化因子（载荷0.990）和体质量因子（载荷0.864）;GD认知损害的危险因子按作用大小依次为携带ε4的基因型（b′=1.097）、TC（b′=0.401）.结论 APOE可能并非GD的发病因子;携带ε4基因型的患者认知功能差,血脂水平高;不同APOE基因型患者有不同的临床表现.

GENE POLYMORPHISM OF APOLIPOPROTEIN E AND CORTICAL CEREBRAL INFARCTION

The polymorphism of apoE, an important determinant in the lipid metabolism, may be related to the atherosclerotic events. In this study, the apoE genotypes, by means of PCR AFLP assay in 42 patients with cortical cerebral infarction and 85 healthy controls were detected. The results showed that the apoE ε 3/3 genotype was more prevalent in the controls (55.29%), and ε 3/4 genotype was more common in the patients (57.14%). The frequency of ε 4 allele was more predominate in the patients than that in the controls. The ε 3/4 genotype or ε 4 allele was associated with 2.44 or 2.31 fold increase in the risk of cortical cerebral infarction. Therefore, it was suggested that apoE ε 4 allele is a genetic factor of susceptibility to cerebral infarction, which supported the hypothesis of the association between apoE polymorphism and atherosclerotic cardio cerebrovascular disorders.

The Gab2 in signal transduction and its potential role in the pathogenesis of Alzheimer’s disease

The growth factor receptor-bound protein 2 （Grb2） -associated binder （Gab） proteins are intracellular scaffolding/ docking molecules,and participate in multiple signaling pathways,usually acting as the downstream effector of protein-tyrosine kinases （PTKs） -triggered signal transduction pathway.When phosphorylated by PTKs,Gab proteins can recruit several signaling molecules （p85,SHP2,and Crk） ,and subsequently activate multiple transmitting signals that are critical for cell growth,survival,differentiation and apoptosis.Recently,it has been reported that Gab2 polymorphism is associated with the increase in the risk of Alzheimer’s disease （AD） and is involved in the pathogenesis of AD.This review mainly focuses on the structure and function of Gab2 protein and its role in the pathogenesis of AD.

Apolipoprotein E polymorphism in the early onset of coronary heart disease

Objective To assess the relationship between apolipoprotein E (apoE) polymorphism and the early onset of coronary heart disease (CHD) and the effect of apoE on lipids and lipoproteins in healthy Chinese subjects. Methods Sixty-eight patients with CHD younger than 55 years (CHD1), 136 patients with CHD older than 65 years (CHD2), and 136 healthy subjects were enrolled, and their plasma levels of triglyceride (TG), total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C) were determined. The apoE genotypes were identified by polymerase chain reaction-restriction fragment length polymorphism. Results apoE 3/4 genotype and E4 allele frequency in the CHD1 group were higher than those in the CHD2 group and healthy subjects, while no differences were found between CHD2 and healthy subjects. Meanwhile, the plasma levels of TC and low density lipoprotein cholesterol (LDL-C) were higher in the CHD2 group than in both CHD1 group and healthy subjects.Each apoE isoprotein has variable TC and LDL-C levels that is E2 (E2/2+E2/3)＜E3(E3/3)<E4(E4/4+E3/4). Conclusion apoE is one of the genetic factors that affect TC and LDL-C levels, and apoE 4 has a very close relation to CHD, suggesting that apoE 4 is an independent genetic factor of the early onset of CHD.

Apolipoprotein E gene polymorphism and its association with human longevity in the Uygur nationality in Xinjiang

Objective To study the relationship between apoE alleles and life-span. Methods Apolipoprotein E genotypes were determined in 164 unrelated Uygurs including 35 persons aged 90 years or older, 71 men aged 20-35 and 54 men with myocardial infarction by using polymerase chain reaction-restriction fragment length polymorphism. Apolipoprotein E gene polymorphism was analyzed among three groups. Results There was statistically significant difference in the ε4 allele frequencies among three groups. The ε4 allele frequency in olds was the lowest (0.057), while in patients suffering from myocardial infarction (MI) was the highest (0.213). In MI patients the average age of first attack in ε4 allele carriers was significantly younger than that of non-carries, 51.3 and 58.3 years, respectively (P<0.05). Conclusion ApoE genotype may have some impact on human longevity.

Influence of electroacupuncture therapy of tonifying the kidney and regulating governor vessel on Aβ related degradation enzymes in the hippocampus of a rat model of Alzheimer's disease induced by Aβ_(1-42)

Objective： To explore influence of electroacupuncture（EA） therapy of tonifying the kidney and regulating governor vessel on amyloid beta（Aβ） related degradation enzymes in the hippocampus of a rat model of Alzheimer＇s disease（AD） induced by Aβ（1-42）.Methods： Forty Wistar male rats were randomly divided into 4 groups： a normal group, a sham operation group, a model group and an EA group, 10 rats in each one. The rats in normal group were normally fed. The rats in sham operation group were bilaterally injected in the hippocampus with 5 μL of saline and they were normally fed after the injection. The rats in the model group and the EA group were bilaterally injected in the hippocampus with 5 μL of Aβ（1-42） on each side. Rats in the EA group received EA of 5 Hz continuous wave at the ＂Bǎihuì（百会 GV20）＂ and bilateral ＂Shènshū（肾俞 BL23）＂ for a duration of 15 min per time every day and continuously for 15 days. After 15 days, the hippocampal expression levels of insulin degrading enzyme（IDE）, lipoprotein（LPL）, transthyretin（TTR）, apolipoprotein E（APoE）,a2 macroglobulin（a2 M） and Aβ（1-42） of the 4 groups were tested by Western blot.Results： Compared with the sham operation group, the expression levels of IDE, LPL, TTR, APoE and a2 M in the hippocampus were significantly lower（P〈 0.05, P〈 0.01） and the expression of Aβ（1-42） was significantly higher（P〈 0.01） in the model group. Compared with the model group, the expression levels of IDE, LPL, TTR,APoE and a2 M in the hippocampus of these rats were significantly lower（P〈 0.05,P〈 0.01）, the expression of Aβ（1-42） was significantly higher（P〈 0.01） in the EA group.Conclusion： EA therapy of tonifying the kidney and regulating governor vessel can enhance the expression of IDE, LPL, TTR, APoE, and a2 M in the hippocampus of AD rats injected by Aβ（1-42）, and may consequently promote the degradation of aβ（1-42） to help improve the pathological manifestations of AD and therefore delay its progression.

Observation of the density and size of cells in hippocampus and vascular lesion in thalamus of GFAP-apoE transgenic mice

Objective Apolipoprotein E （apoE） is associated with increased risk of age-related diseases, such as Alzheimer＇s disease （AD） and cerebrovascular disease （CVD）. The present study aims to investigate the age-related general morphological changes of the brain in GFAP-apoE transgenic mice, especially the alterations in number and size of hippocampal pyramidal cells and the microvascular lesions in the thalamus. Methods Nine female apoE4/4 mice were divided into 3 groups （n=3 in each group）： 3-4 months （young group）, 9-10 months （middle-aged group） and 20-21 months （old group）. Age-matched apoE3/ 3 mice were employed as control group （n=3 in each group）. The paraffin sections of brain tissue were stained by 2 conventional staining methods, thionin staining and hematoxylin-esion（HE） staining, the former of which was to observe the hippocampal cells, while the latter was used to examine the brain microvasculature. Results There was no apparent difference in the cortical layer between apoE3/3 and apoE4/4 mice, neither any significant difference in the number of cells in hippocampal CA1-CA3 subfields between apoE3/3 and apoE4/4 mice at various age points （P 〉 0.05）. However, the mean size of pyramidal cells in CA1 subfield in apoE3/3 and apoE4/4 mice decreased as mice were getting older （P 〈 0.001）. At the age of 20-21 months, this cellular atrophy in apoE4/4 mice was more severe than that in old apoE3/3 mice （P 〈 0.05）. Furthermore, microvascular lesion in the thalamus was detected in all the 3 old apoE4/4 mice, at varying degrees （5.24%, 1.41% and 3.97%, respectively）, while only one apoE3/3 mouse exhibited microvascular lesion in the thalamus, at a low level （0.85%）. Conclusion The current study suggests that the cell size in hippocampal CA1 subfield decreases with aging, irrespective of apoE genotype. Cellular atrophy in CA1 subfield and the microvascular lesion in the thalamus are both more severe in old apoE4/4 mice as compared with those in age-matched apoE3/3 mice. Doubts still exist on whether the decreased cell size in hippocampal CA1 subfield in old apoE4/4 mice is associated with dysfunction in learning and memory and whether the microvascular lesions indicate a higher risk of stroke in human apoE4 allele mice. To clarify these issues, further investigations are needed.

Genetic susceptibility to traumatic brain injury and apolipoprotein E gene

Traumatic brain injury （TBI） is defined as an injury caused by a blow or jolt to the head or a penetrating head injury that disrupts the normal function of the brain. It is a common emergency and severe case in neurosurgery field. Nowadays, there are more and more evidences showing that TBI, which is apparently similar in pathology and severity in the acute stage, may have different outcomes. The known prognostic factors （such as age, severity of injury and treatments, etc.） explain only part of this variability and the concept of genetic susceptibility of traumatic brain injury has already been accepted by more and more people. It is now demonstrated that genetic polymorphism may play a key role in the susceptibility to TBI, even outcome follow-ing TBI. Although there are many genes that may involved in pathophysiological processes influencing TBI, apolipoprotein E gene has become one of the most extensive studied genes in neurotrauma and neurodegenerative disease and seems to take an important part in the neural responses to TBI. In this article, we will review the current understanding of the genetic susceptibility of TBI and the advancements regarding the impact of apolipoprotein E genotype on the severity and/or outcome following TBI.