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肾上腺髓质素减轻载脂蛋白E^(-/-)小鼠动脉粥样硬化发生发展
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作者 潘春水 于芳 +4 位作者 赵晶 陈丽 曹长琦 唐朝枢 齐永芬 《中国动脉硬化杂志》 CAS CSCD 2007年第7期534-534,共1页
关键词 病理学与病理生理学 肾上腺髓质素 动脉粥样硬化 降钙素受体样受体 受体活性修饰蛋白 载脂蛋白E^-/^- 小鼠
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辛伐他汀减轻载脂蛋白E^(-/-)小鼠氧化应激及小窝蛋白1的表达 被引量:1
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作者 尹冬华 桂鸣 +1 位作者 刘猛 黄峻 《中华高血压杂志》 CAS CSCD 北大核心 2008年第8期700-703,共4页
背景氧化应激损伤内皮是动脉粥样硬化的始动因素,他汀对于动脉粥样硬化的干预主要集中在粥样硬化斑块形成之后,而对于粥样硬化斑块形成之前的研究较少。目的观察辛伐他汀对载脂蛋白(apo)E^(-/-)小鼠氧化应激及主动脉内皮小窝蛋白l的影响... 背景氧化应激损伤内皮是动脉粥样硬化的始动因素,他汀对于动脉粥样硬化的干预主要集中在粥样硬化斑块形成之后,而对于粥样硬化斑块形成之前的研究较少。目的观察辛伐他汀对载脂蛋白(apo)E^(-/-)小鼠氧化应激及主动脉内皮小窝蛋白l的影响,探讨辛伐他汀在动脉粥样硬化一级预防中保护内皮功能的机制。方法24只6周龄雄性 apoE^(-/-)小鼠,随机等分为两组:对照组、辛伐他汀[5 mg/(kg·d)]治疗组,4周后处死动物。常规生物化学法测定血总胆固醇(TC)、超氧化物歧化酶活性(SOD)、丙二醛(MDA)和血清一氧化氮(N0)含量。采用苏木素伊红(HE)染色法观察小鼠主动脉内皮组织,免疫组织化学法分析小鼠主动脉内皮的小窝蛋白1的表达。结果两组间血脂水平无显著性差异。辛伐他汀治疗组主动脉内皮组织的损伤减轻(损伤阳性率33.3%比对照组:75%,P<0.05)。治疗4周后,辛伐他汀治疗组 SOD[(135.3±5.5)U/L 比对照组:(97.2±7.6)U/L,P<0.01)和 NO[(28.4±4.1)μmol/L 比对照组:(12.3±2.1)μmol/L,P<0.01]均明显升高,MDA 显著减低[(10.5±0.5)nmol/L 比对照组:(17.3±1.0)nmol/L,P<0.01]。辛伐他汀治疗组主动脉内皮上小窝蛋白1的表达(表达阳性率41.67%比对照组:83.33%,P<0.05)明显降低。结论辛伐他汀在不影响血脂水平情况下,抑制主动脉内皮的小窝蛋白1的表达,减轻 apoE^(-/-)小鼠氧化应激,增加 NO 水平,起到改善内皮功能、抗动脉粥样硬化作用,在动脉粥样硬化的一级预防中可能发挥重要作用。 展开更多
关键词 辛伐他汀 载脂蛋白E^-/-小鼠 氧化应激 小窝蛋白1
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脂蛋白脂酶基因缺陷促进载脂蛋白E^(-/-)糖尿病小鼠动脉粥样硬化及糖尿病肾病的进展 被引量:1
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作者 周晓琳 王兆红 +1 位作者 刘国庆 黄薇 《中国动脉硬化杂志》 CAS CSCD 北大核心 2009年第7期599-599,共1页
关键词 蛋白脂酶 糖尿病 载脂蛋白E^-/-小鼠 动脉粥样硬化 糖尿病肾病
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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 被引量:7
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作者 吴祖荣 陈宗存 +5 位作者 符茂雄 陈金逸 韩隆元 周丽华 黄亚莲 王毅 《临床和实验医学杂志》 2015年第12期982-985,共4页
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... 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。 展开更多
关键词 2型糖尿病 冠心病 基因多态性 META分析
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The Effects of Apolipoprotein E Polymorphism on Serum Lipids, Lipoproteins and Apolipoproteins Variation 被引量:3
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作者 潘闽 朱健华 +2 位作者 袁瑾 王惠民 刘志华 《Journal of Nanjing Medical University》 2003年第4期196-200,共5页
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 l... 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. 展开更多
关键词 Apolipoprotein E POLYMORPHISM polymerase chain reaction restrictionfragment length polymorphism
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载脂蛋白E基因多态性与老年期抑郁症的关联性 被引量:8
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作者 宗小芬 胡茂林 +3 位作者 唐劲松 李宗昌 陈晓岗 方润领 《中华行为医学与脑科学杂志》 CAS CSCD 北大核心 2015年第4期319-322,共4页
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 polymorp... 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. 展开更多
关键词 老年期抑郁症 基因多态性 认知功能 血脂
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GENE POLYMORPHISM OF APOLIPOPROTEIN E AND CORTICAL CEREBRAL INFARCTION
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作者 张颖冬 梁秀龄 《Chinese Medical Sciences Journal》 CAS CSCD 1998年第4期248-251,共4页
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 ... 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. 展开更多
关键词 apolipoprotein E POLYMORPHISM cerebral infarction
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The Gab2 in signal transduction and its potential role in the pathogenesis of Alzheimer’s disease
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作者 潘小玲 任汝静 +2 位作者 王刚 汤荟冬 陈生弟 《Neuroscience Bulletin》 SCIE CAS CSCD 2010年第3期241-246,共6页
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 ... 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. 展开更多
关键词 Gab2 signal transduction Alzheimer’s disease APOE
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Apolipoprotein E polymorphism in the early onset of coronary heart disease
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作者 杨志健 朱铁兵 +5 位作者 马根山 尹航 钱卫冲 张馥敏 曹克将 马文珠 《Chinese Medical Journal》 SCIE CAS CSCD 2001年第9期87-89,110,共4页
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. Met... 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. 展开更多
关键词 coronary heart disease · early onset · apolipoprotein E · polymorphism
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Apolipoprotein E gene polymorphism and its association with human longevity in the Uygur nationality in Xinjiang 被引量:1
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作者 王新利 王国荃 +1 位作者 杨春荣 李萱 《Chinese Medical Journal》 SCIE CAS CSCD 2001年第8期34-37,104,共5页
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 5... 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. 展开更多
关键词 apolipoprotein E · gene · longevity · Uy gur
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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) 被引量:12
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作者 Yan-jun DU a Shuang-hong TANG a a +3 位作者 Jia-huan XIAO a Yun WANG a Qing TIAN b Guo-jie SUN 《World Journal of Acupuncture-Moxibustion》 CSCD 2018年第3期185-190,I0004,I0005,共8页
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 Alzhe... 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. 展开更多
关键词 Tonifying the kidney and regulating governor vessel EA Alzheimer's Disease Amyloid Beta (Aβ) protein Insulin degrading enzyme LIPOPROTEIN TRANSTHYRETIN Apolipoprotein E Alpha-2 Macroglobulin
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Observation of the density and size of cells in hippocampus and vascular lesion in thalamus of GFAP-apoE transgenic mice
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作者 唐克峰 蔡莉 周江宁 《Neuroscience Bulletin》 SCIE CAS CSCD 2009年第4期167-178,共12页
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-rel... 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. 展开更多
关键词 apolipoprotein E AGING microvascular lesion Alzheimer's disease
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Genetic susceptibility to traumatic brain injury and apolipoprotein E gene 被引量:5
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作者 孙晓川 江涌 《Chinese Journal of Traumatology》 CAS 2008年第4期247-252,共6页
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 neur... 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. 展开更多
关键词 Brain injuries Genetic predisposition to disease GENES
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SR1001抑制白细胞介素-17相关炎性反应减缓小鼠腹主动脉瘤进展的研究
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作者 王淑霞 肖杰 +3 位作者 陈星 杨传蕾 陈卫强 魏战杰 《中华实验外科杂志》 CAS CSCD 北大核心 2018年第11期2042-2044,共3页
目的探讨SR1001药物干预对血管紧张素Ⅱ(AngⅡ)诱导的载脂蛋白E(ApoE^-/-)小鼠实验性腹主动脉瘤模型的作用及其机制。方法45只雄性ApoE^-/-小鼠随机分为对照组(Sham组)、AngⅡ模型组(Control组)和AngⅡ+SR1001治疗组(SR1001... 目的探讨SR1001药物干预对血管紧张素Ⅱ(AngⅡ)诱导的载脂蛋白E(ApoE^-/-)小鼠实验性腹主动脉瘤模型的作用及其机制。方法45只雄性ApoE^-/-小鼠随机分为对照组(Sham组)、AngⅡ模型组(Control组)和AngⅡ+SR1001治疗组(SR1001组)。所有小鼠从术前1~28d均接受0.5%二甲基亚砜(DMSO)或SR1001溶液腹腔注射治疗,各组小鼠分别于术后第0、14、28天对小鼠进行腹主动脉直径超声测量,评估腹主动脉瘤形成情况。术后第28天收取小鼠腹主动脉,进行弹性纤维染色(EVG)、免疫荧光染色[anti-CD4、白细胞介素-17(IL-17)]等组织学分析、Western blot蛋白检测相关炎性因子如IL-17、单核细胞趋化蛋白-1(MCP-1)、γ-干扰素(IFN-1)的表达。结果(1)与Control组比较,SR1001组的腹主动脉瘤的形成率显著降低(33.3%比73.3%,X^2=4.821,P=0.028)及腹主动脉直径显著减小[(1.39±0.06)mm比(1.98±0.11)mm,P=0.009]。与Sham组比较,SR1001组腹主动脉直径差异并无统计学意义[(1.39±0.06)mm比(1.07±0.08)mm,P=0.064]。(2)通过EVG染色组织学分析,与Control组比较,SR1001组通过SR1001药物干预明显地保护了血管壁结构(P=0.018)。(3)与Control组比较,SR1001组中腹主动脉组织中CD4^+/IL-17^+细胞(Th17细胞)的浸润明显地减少。(4)与Control组比较,SR100组炎性因子IL-17、MCP-1、IFN-1的蛋白表达得到明显抑制(分NP=0.008、0.016、0.023)。结论SR1001干预由AngⅡ诱导的ApoE^-/-小鼠实验性腹主动脉瘤模型可以有效抑制炎性因子的表达及炎性细胞浸润,有效地保护血管组织,减缓实验性腹主动脉瘤的发展。 展开更多
关键词 SR1001 血管紧张素Ⅱ 载脂蛋白E^-/-小鼠 白细胞介素-17 炎性细胞 实验性腹主动脉瘤模型
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