尼麦角林通过调节海马 CA1区单胺类递质受体表达和血清载脂蛋白 E4水平改善血管性抑郁大鼠的抑郁行为

目的：探讨尼麦角林对血管性抑郁（vascular depression,VD）模型大鼠海马CA1区5-羟色胺1A受体（5-hydroxytryptamine 1A receptor,5-HT1A R）、多巴胺 D2受体（ D2 dopamine receptor, D2DR）、肾上腺素能α2A受体（α2A-adrenergic receptor,α2AAR）表达和血清载脂蛋白（apolipoprotein E4, ApoE4）水平的影响。方法48只雄性Sprague-Daw ley 大鼠随机分为正常对照组、模型组、氟西汀组以及尼麦角林小量组、中剂量组和大剂量组,每组8只。采用双侧颈总动脉结扎叠加慢性不可预见性温和应激（chronic unpredictable mild stress, CUMS ）加孤养建立VD模型。正常对照组不CUMS也不孤养,模型组CUMS 并孤养。氟西汀组在开始CUMS和孤养时给予氟西汀1.3 mg/（kg· d）灌胃,共3周;尼麦角林小剂量、中剂量和大剂量组在开始CUMS 和孤养时分别给予尼麦角林0.9、1.9和3.8 mg/（kg· d）灌胃,共3周;正常对照组和模型组等体积蒸馏水灌胃,1次/d,共3周。蔗糖溶液消耗和旷野试验评价抑郁样行为,免疫组化染色法和蛋白印迹法检测海马CA1区5-HT1AR、D2DR、α2AAR表达,酶联免疫法检测血清ApoE4水平。结果 CUMS 前,模型组、氟西汀组和各尼麦角林组水平运动和垂直运动评分、蔗糖溶液消耗均较正常对照组显著降低（P均＜0.01）;而CUMS 后21 d,氟西汀组和尼麦角林中剂量和大剂量组均显著高于模型组（P均＜0.05）,氟西汀组以及各尼麦角林组之间无统计学差异。模型组、氟西汀组和各尼麦角林组5-HT 1A R、D2 DR、α2A AR表达和血清ApoE4水平均显著高于正常对照组,氟西汀组、尼麦角林中剂量和大剂量组均显著低于模型组（P均<0.01）,而氟西汀组以及各尼麦角林组无统计学差异。结论尼麦角林可改善VD大鼠抑郁样行为,其机制可能与下调海马CA1区5-HT1AR、D2DR、α2AAR表达和血清ApoE4水平有关。     

人血浆载脂蛋白AⅠ的纯化

 目的  初探大规模纯化人血浆载脂蛋白AⅠ(apolipoprotein AⅠ,ApoAⅠ）的低成本生产工艺。方法  以人血浆组分Ⅳ为原料,通过等电点沉淀、阴离子层析、低温乙醇沉淀和超滤等步骤纯化ApoAⅠ蛋白,并放大实验室纯化方法来纯化ApoAⅠ。结果  放大的纯化方法生产的ApoAⅠ的得率和纯度分别为59.0%和85.6%,经相关方法验证为人血浆ApoAⅠ。结论  实验室方法放大的纯化工艺可纯化ApoAⅠ。     

脑梗死患者脉搏波速度与载脂蛋白、胆红素、尿酸的相关性

目的探讨脑梗死患者脉搏波速度与血脂、尿酸及胆红素的相关性。方法选择脑梗死组和健康对照组各30例,进行脉搏波速度、血脂、胆红素、尿酸的测定。结果脑梗死组脉搏波速度、尿酸明显高于对照组,胆红素明显低于对照组,差异有统计学意义（P〈0.05）。脑梗死组总胆固醇及甘油三酯、低密度脂蛋白均高于对照组,但差异没有明显统计学意义,脑梗死组的载脂蛋白B/载脂蛋白A大于对照组,差异有统计学意义。推断脑梗死患者脉搏波速度与载脂蛋白B/载脂蛋白A（ApoB/ApoA）及尿酸呈正相关,与间接胆红素呈负相关。结论脑梗死患者的脉搏波速度明显快于对照组,且与载脂蛋白、胆红素及尿酸均有相关性,脉搏波速度可作为脑梗死危险度的预测因子。     

载脂蛋白A5基因的研究进展

血脂水平异常是冠心病、脑卒中等动脉粥样硬化性疾病的一个重要危险因素。血脂异常其实质是脂蛋白和载脂蛋白的异常。载脂蛋白A5基因自2001年被发现以来,证实其对调控三酰甘油水平有重要影响。现将载脂蛋白A5的结构功能、调控机制以及载脂蛋白A5基因单核苷酸多态性与血脂、冠心病的关系予以综述。     

Role of DNA damage in atherosclerosis--bystander or participant?

Atherosclerosis leading to cardiovascular disease is the leading cause of death among western populations. Atherosclerosis in characterised by the development of a fibrofatty lesion that consists of a diverse cell population, including inflammatory cells that create an intensely oxidising environment within the vessel. Coupled with normal replication, the local intracellular and extracellular environment causes damage to cellular DNA that is recognised and repaired by the DNA damage response (DDR) pathway. The role of DNA damage and the resulting deregulation of ‘normal’ cellular behaviour and subsequent loss of cell cycle control checkpoints have been widely studied in cancer. However, despite the extensive evidence for DNA damage in atherosclerosis, it is only over the past two decades that a causative link between DNA damage and atherosclerosis has been hypothesised. Whilst atherosclerosis is a feature of human disease characterised by defects in DNA damage, currently the role of DNA damage in the initiation and progression of atherosclerosis remains highly debated, as a ‘chicken and egg’ situation. This review will analyse the evidence for, the causes of, and consequences of DNA damage in atherosclerosis, detail the DNA damage response pathway that results in these consequences, and highlight therapeutic opportunities in this area. We also outline the evidence that DNA damage is a cause of both initiation and progression of atherosclerosis, and not just a consequence of disease.     

载脂蛋白CⅢ基因多态性频率分布及与高脂血症患者关系的研究

目的探讨ApoCIII基因中,ApoCIII3175、ApoCIII3206基因型及等位基因频率及其与原发性高脂血症患者的相关性。方法采用病例-对照相关性研究策略,选择昆明地区汉族作为研究对象,对91例高脂血症患者及76例健康对照者进行了上述基因多态性检测。结果①76例健康者中,ApoCIII3175位点的CC、CG、GG基因型频率分别是0.421、0.553、0.026;C和G等位基因频率分别是0.697、0.303。ApoCIII3206位点的GG、GT、TT基因型频率分别是0.671、0.276、0.053;G和T等位基因频率分别是0.809、0.191。②91例高脂血症患者中,ApoCIII3175（CC、CG、GG）、ApoCIII3175（GG、GT、TT）位点的基因型和等位基因多态性频率与对照组比较,差异无显著性意义（p〉0.05）。③昆明地区91例高脂血症患者中的TC、TG、HDL-C、LDL-C水平在ApoCIII3175、ApoCIII3206各位点不同基因型间比较,差异无显著性意义（p〉0.05）。结论昆明地区汉族健康人群ApoCIII3175、ApoCIII3206基因多态性有地区特征;该地区汉族高脂血症患者中的ApoCIII3175、ApoCIII3206基因多态性可能与高脂血症可能有一定关联。     

载脂蛋白E在蛛网膜下腔出血发病机制的研究

目的:研究血清载脂蛋白E(ApoE)、血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)与蛛网膜下腔出血(SAH)严重程度和预后的关系。方法:选取我院2005年-2008年诊断为SAH住院患者47例为实验组,同时选取年龄性别相匹配的健康体检者47例为对照组,两组均测定空腹肘静脉血清ApoE、TC、TG、HDL-C、LDL-C。结果:SAH患者血清ApoE水平随着病情的加重而增加,但与正常对照组相比差异无显著性;与预后良好组比较,预后不良组血清LDL、TC水平明显上升,具有显著性差异。结论:血清ApoE对SAH发病无明显影响;SAH患者的LDL、TC水平升高,与病情严重程度显著相关。     

载脂蛋白A-Ⅰ在8种不同组织学分型肾肿瘤中的表达

目的：研究载脂蛋白A-Ⅰ（apolipoprotein A-Ⅰ,ApoA-Ⅰ）在8种不同组织学分型的肾肿瘤组织中的表达情况,探索用于鉴别诊断的新型肿瘤标志物。方法：应用免疫组织化学方法检测23例肾肿瘤（包括透明细胞癌11例、乳头状细胞癌1例、嫌色细胞癌3例、嗜酸细胞腺癌1例、多房性囊性细胞癌2例、肾盂尿路移行上皮癌3例、后肾腺癌1例、集合管癌1例）及5例癌旁正常组织中ApoA-Ⅰ的表达,癌旁正常组织取自除外23例肾癌组织的其他5例肾肿瘤的切缘外非癌组织。结果：23例肾肿瘤中,ApoA-Ⅰ阳性21例(阳性率91.3%);肾癌旁组织5例,阳性2例(阳性率40.0%),ApoA-Ⅰ在肿瘤组织与癌旁正常组织中的表达差异有统计学意义(Z=－2.829,P=0.003)。比较不同组织学分型的肾肿瘤,11例肾透明细胞癌中,阳性9例(阳性率81.8%), ApoA-Ⅰ的表达程度与肿瘤细胞的恶性程度有关,透明细胞癌Ⅱ级、Ⅲ级的表达程度明显高于Ⅰ级,差异有统计学意义(Z=－2.070,P=0.038);乳头状细胞癌、嫌色细胞癌、嗜酸细胞腺癌、多房性囊性细胞癌、肾盂尿路移行上皮癌、后肾腺癌、集合管癌均有不同程度的阳性着色。结论：ApoA-Ⅰ在肾肿瘤组织中的表达特异升高,可作为区分不同组织学分型肾肿瘤的免疫组织化学标志物。     

Pediatric fatty liver disease: Role of ethnicity and genetics

Non-alcoholic fatty liver disease (NAFLD) comprehends a wide range of conditions, encompassing from fatty liver or steatohepatitis with or without fibrosis, to cirrhosis and its complications. NAFLD has become the most common form of liver disease in childhood as its prevalence has more than doubled over the past 20 years, paralleling the increased prevalence of childhood obesity. It currently affects between 3% and 11% of the pediatric population reaching the rate of 46% among overweight and obese children and adolescents. The prevalence of hepatic steatosis varies among different ethnic groups. The ethnic group with the highest prevalence is the Hispanic one followed by the Caucasian and the African-American. This evidence suggests that there is a strong genetic background in the predisposition to fatty liver. In fact, since 2008 several common gene variants have been implicated in the pathogenesis of fatty liver disease. The most important is probably the patatin like phospholipase containing domain 3 gene (PNPLA3) discovered by the Hobbs’ group in 2008. This article reviews the current knowledge regarding the role of ethnicity and genetics in pathogenesis of pediatric fatty liver.     

狼疮肾炎患者肾组织中载脂蛋白E的表达及意义

目的 了解狼疮肾炎(LN)肾组织中载脂蛋白E(APOE)的表达,并探讨其与LN肾脏病理改变和肾功能损害的关系.方法 用免疫组织化学方法对40例LN患者.肾组织APOE的表达进行检测,并对其与LN的肾脏病理改变和肾功能损害的相关性进行分析.结果 健康肾脏组织有较弱的ApoE表达;LN肾组织APOE的表达较健康肾组织明显增高[肾小球(31.2±11.0)与(3.0±1.6);肾小管(71.64±8.90)与(0.60±0.06)],并且Ⅳ型LN患者肾组织APOE表达量高于非Ⅳ型LN患者[肾小球(38.4±4.5)与(18.0±4.6);肾小管间质(77.6±2.5)与(60.0±3.2)];Spearman相关分析显示LN肾组织ApoE的表达与LN肾脏病理活动指数和肾功能呈显著相关(P＜0.01).结论 LN患者肾脏组织中ApoE的表达增高,尤以Ⅳ型LN为著,其表达量可反映LN肾脏活动性病变及肾脏损害情况.