家族性高胆固醇血症合并极高危ASCVD 1例

本研究报道了1例29岁男性家族性高胆固醇血症(FH)患者,血浆低密度脂蛋白胆固醇(LDL-C)异常升高、合并黄色瘤且早发冠心病。遗传学分析显示该患者发生了低密度脂蛋白受体(LDLR)编码基因的复合杂合突变,属一种极其罕见的基因突变类型,该变异导致LDLR自身表达、摄取及结合LDL-C功能受损,使前蛋白转化酶枯草溶菌素9型(PCSK9)抑制剂效果不佳。基于遗传学诊断,个体化的给予患者PCSK9抑制剂、最大可耐受剂量他汀和依折麦布,并成功接受了冠状动脉介入治疗。     

家族性高胆固醇血症研究现状

家族性高胆固醇血症(FH)是一种常染色体显性遗传病,其在我国的诊治情况不容乐观,诊断率和治疗率都不尽如人意。该文主要介绍我国FH的诊疗现状和基因学研究概况,探讨国外重要的诊断标准和疾病的特点及预后,并就FH治疗及管理的方法进行讨论。     

家族性高胆固醇血症的基因治疗

家族性高胆固醇血症的基因治疗黎健（卫生部北京老年医学研究所北京医院，１００７３０）家族性高胆固醇血症（ＦＨＣ）是一种ＬＤＬ受体缺失的遗传性疾病，根据ＬＤＬ受体两个等位基因缺失的程度不同，分为杂合子和纯合子型。在杂合子型病人，由于一个等位基因的异常而引...     

家族性高胆固醇血症的早期诊断与治疗

家族性高胆固醇血症是一种常染色体共显性遗传疾病 ,是脂质代谢疾病中最严重的一种 ,常伴有高胆固醇血症和提早发生的动脉粥样硬化 ,是冠脉疾病发生的一种重要危险因素。本文综述了家族性高胆固醇血症的临床特点、诊断及治疗 ,并提出了早期诊断与有效治疗对部分消除或阻滞冠脉病变发展的重要性。     

家族性高胆固醇血症的病例检测和诊断

杂合子家族性高胆固醇血症（ｈＦＨ）是冠脉疾病发生的一个重要的危险因素。本文认为根据ＷＨＯ标准，ｈＦＨ可作为一种应该普查的疾病。     

家族性高胆固醇血症诊治的研究进展

家族性高胆固醇血症(FH)是指由基因突变导致血浆低密度脂蛋白胆固醇水平明显升高的疾病。FH患者临床表现为皮肤、肌腱黄色素瘤或角膜弓等,也可出现心血管系统受累,严重者甚至导致急性心肌梗死等疾病。因此,对FH进行早期识别、诊断和治疗尤为重要。本文就FH的分子病理基础以及疾病的诊断和治疗的研究进展作一综述。     

家族性高胆固醇血症诊治新进展

家族性高胆固醇血症(familial hypercholesterolemia,FH)是一种常染色体显性遗传性疾病,其主要病理基础是低密度脂蛋白受体、前蛋白转换酶枯草溶菌素9、载脂蛋白B和低密度脂蛋白受体衔接蛋白1等基因突变。FH的发病率较高,危害性大,是早发冠心病的重要原因。     

有关家族性高胆固醇血症的治疗问题

家族性高胆固醇血症出现于新生儿直至老年人，而且表现多种多样。通常由普内科或儿内科医师作出诊断，然后由专科医师对纯合子患者和难治性杂合子患者进行进一步的诊断和治疗。     

家族性高胆固醇血症及其治疗的研究进展

家族性高胆固醇血症（familial hypercholesterolemia, FH）由于基因突变引起血浆低密度脂蛋白（low－density lipoprotein,LDL-C）水平明显升高。患者常出现皮肤、肌腱黄色素瘤或眼底变化;同时可出现心血管系统受累,甚至导致急性心肌梗死。对FH的早期识别、早期诊断和治疗,进一步通过提高公众认知来促进FH的临床管理,对改善疾病预后尤其重要。因此,本文将对近年来FH及其治疗的相关研究作一综述。     

家族性高胆固醇血症患者饮食治疗的重要性

家族性高胆固醇血症（ＦＨ）的饮食治疗旨在降低血浆低密度脂蛋白（ＬＤＬ）胆固醇水平，是各种药物治疗的基础。合理的方案是：胆固醇（１００ｍｇ／日），总脂肪（占热卡的２０％），碳水化合物（６５％），蛋白质（１５％）。这种低脂肪、高碳水化合物饮食能降低血浆胆固醇１８～２１％。     

慢性不可预知温和应激联合高脂饮食对大鼠血小板5-羟色胺的影响

目的探讨慢性不可预知温和应激联合高脂饮食对血小板5-羟色胺的影响。方法 48只雄性SD大鼠随机均分为对照组、应激组、高脂组和高脂应激组,共饲养9周。高脂组和高脂应激组喂食高脂饲料,在实验开始时予维生素D3(60万U/kg)一次性腹腔注射,丙基硫氧嘧啶每天灌胃。对照组和应激组喂食基础饲料,在实验开始时予等量生理盐水一次性腹腔注射,生理盐水每天灌胃。第3周开始,应激组和高脂应激组给予慢性不可预知温和应激,共7周。在实验第9周末,取股动脉血测定血小板5-羟色胺含量。结果经析因分析,慢性不可预知温和应激对大鼠血小板5-羟色胺降低有明显影响(P<0.05),高脂饮食对血小板5-羟色胺无明显影响(P>0.05),二者之间无交互效应(P>0.05)。结论慢性不可预知温和应激降低大鼠血小板5-羟色胺含量,高脂饮食对大鼠血小板5-羟色胺没有影响,二者之间没有交互作用。     

甜菜碱对鹌鹑高脂饮食性脂肪肝的影响

背景：甜菜碱可改善酒精性肝病和非酒精性脂肪性肝病患者的血清生化指标和肝组织学变化，但其机制尚不明确。目的：研究甜菜碱对鹌鹁高脂饮食性脂肪肝的影响。方法：制备鹌鹁高脂饮食性脂肪肝动物模型，以甜菜碱干预后，观察其血清、肝脂质、肝功能生化指标和脂质过氧化指标的变化，并观察肝组织学改变。结果：予高脂饮食性脂肪肝鹌鹁甜菜碱0．2—0．8g／kg治疗6周后，其血清总胆固醇、三酰甘油、低密度脂蛋白．胆固醇、游离脂肪酸水平、肝重指数、肝组织总胆固醇均显著降低（P〈0．05或P〈0．01）；肝组织超氧化物歧化酶活性升高（P〈0．01）；0．8g/kg甜菜碱组可升高血清高密度脂蛋白．胆固醇水平（P〈0．05），降低肝组织三酰甘油和丙二醛含量（P〈0．01）。组织病理学检查结果显示，甜菜碱可使肝细胞脂肪变性程度明显减轻（P〈O．05或P〈0.01），0．8g／kg组的肝细胞结构趋于正常。结论：甜菜碱对鹌鹁高脂饮食性脂肪肝有较好的治疗作用，其部分机制可能是通过抗脂质过氧化和增加脂质代谢实现的。     

急性束缚应激对大鼠结肠敏感性的影响

背景:内脏高敏感性是肠易激综合征(IBS)重要的病理生理特征,而应激事件能诱发或加重IBS患者的症状。目的:了解急性束缚应激对大鼠结肠敏感性的影响和持续时间,以及对单个平滑肌细胞收缩活动的影响。方法:建立急性部分束缚应激大鼠动物模型,于0天(应激前1天)、1天(应激当天)、2天(应激后1天)行结直肠气囊扩张．并行腹壁回撤反射(AWR)评分;分离平滑肌细胞,测定结肠平滑肌细胞的收缩百分率。结果:20 mm Hg和40 mm Hg扩张压力下,束缚组1天的AWR评分显著高于对照组(1．68±0．79对0．81±0．42、2．45±0．72对1．58±0．60,P<0．05);束缚组大鼠1天时AWR评分在20 mm Hg(P1=0．001;P3=0．006)和40 mm Hg(P2=0．012,P4=0．033)扩张压力下与0天、 2天相比显著增加,但在60 mm Hg和80 mm Hg扩张压力下以及对照组在每天的评分均无显著差异;束缚组结肠平滑肌细胞的收缩百分率与对照组无显著差异(P=0．523)。结论:急性束缚应激使大鼠结肠对低压力球囊扩张的敏感性呈一过性增加,对大鼠单个平滑肌细胞的收缩活动没有影响。     

运动对高脂饮食诱导的肥胖大鼠胰岛素抵抗的影响

目的：研究游泳运动对高脂饮食诱导的肥胖大鼠胰岛素抵抗和血清脂肪因子及TNF-α和IL-1的作用。方法：雄性Wistar大鼠随机分为3组：正常饮食组（RD）、高脂饮食组（HFD）和高脂饮食后运动组（HFDE）,游泳运动训练前后检测大鼠胰岛素抵抗指数（HOMA-IR）和血清脂肪因子及TNF-α、瘦素（leptin）与IL-1的水平。结果：与HFD组相比,游泳运动降低了HFDE组的HOMA-IR（14．2±1．2vs7．9±0．8,P〈0．05）,降低了血清脂肪因子及TNF-α和IL-1的水平（FFA：0．4±0．1vs0．6±0．2mmol／L,leptin：1．6±0．8VS2．9±0．9ng／ml,TNF-α：92．0±18．8VS101．3±23．8pg／ml,IL-1：45．8±10．4 vs72．1±13．7pg／m1,P均〈0．05）。结论：运动降低了高脂饮食诱导的肥胖大鼠的血清脂肪因子以及leptin、TNF-α和IL-1水平,改善了胰岛素抵抗。     

流体剪切力对5-氮杂胞苷诱导大鼠骨髓间充质干细胞向心肌样细胞分化的影响

目的观察5-氮杂胞苷诱导大鼠骨髓间充质干细胞向心肌样细胞分化,并探讨流体剪切力对诱导过程的影响。方法贴壁法从大鼠骨髓中分离骨髓间充质干细胞,进行纯化传代培养,取第4代骨髓间充质干细胞以3、5、10、15及20μmol/L 5-氮杂胞苷分别作用12、24及48 h,用免疫荧光法鉴定分化的心肌样细胞α-肌动蛋白表达率,10μmol/L作用24 h为最佳诱导浓度。通过建立流体剪切力模型,设立以下四组:不加载流体剪切力组、加载5 dyn/cm2流体剪切力组、加载15 dyn/cm2流体剪切力组和加载25 dyn/cm2流体剪切力组,作用24 h,倒置显微镜观察诱导后骨髓间充质干细胞形态的变化,4周后逆转录聚合酶链反应测定分化的心肌样细胞心肌肌钙蛋白ImRNA的表达。结果骨髓间充质干细胞随着传代逐渐变成梭形,5-氮杂胞苷诱导后骨髓间充质干细胞胞体逐渐增大并伸出细长突起,部分相邻细胞的突起连接成网,形态学上表现出向心肌细胞方向转化的特征。免疫荧光显示α-肌动蛋白表达阳性。经过流体剪切力作用细胞后,心肌肌钙蛋白I的表达增高,阳性条带均比未进行力学刺激的细胞表达明显,以15 dyn/cm2剪切力最明显。但是25 dyn/cm2剪切力作用结果并没有随着力的增大而增大。结论 5-氮杂胞苷可以诱导大鼠骨髓间充质干细胞向心肌样细胞分化,5-氮杂胞苷可联合剪应力诱导大鼠骨髓间充质干细胞向心肌样细胞分化,且诱导效果优于单独使用5-氮杂胞苷。     

Effect of Dietary Fat on Chronic Ethanol-Induced Oxidative Stress in Hepatocytes

BACKGROUND: Although oxidative stress and deficits in hepatic energy metabolism have been implicated as important factors in the initiation of alcoholic liver disease, their relative contribution to ethanol-induced cell death is not known. The purpose of this study was to examine the effects of chronic ethanol administration on hepatocyte reactive oxygen species (ROS) generation, energy state, and viability, as well as the effect of dietary fat on these parameters. METHODS: Male Sprague-Dawley rats were fed liquid diets that provided 36% total calories as ethanol, with fat as either 12% (low fat) or 35% (high fat) of total calories. Pair-fed controls received liquid diets in which maltose-dextrin was substituted for ethanol calories. The fluorescent probe 2',7'-dichlorofluorescin diacetate was used to detect ROS, lactate dehydrogenase leakage was used to assess viability, and ATP levels were used as a measure of the energy state. The effect of chronic ethanol feeding on these parameters was determined by incubating hepatocytes under a 5% oxygen-containing atmosphere or an atmosphere < or = 1% oxygen for 60 min. RESULTS: In general, chronic ethanol feeding stimulated ROS production and decreased ATP concentrations, which were associated with decreased viability in hepatocytes isolated from rats fed either high- or low-fat, ethanol-containing diets, compared to the corresponding controls. Incubation under an atmosphere < or = 1% oxygen and/or ethanol (10 mM) augmented these effects in both high- and low-fat control and ethanol-fed hepatocytes. The addition of antimycin to the incubations increased ROS production, decreased ATP concentrations, and accelerated loss of hepatocyte viability. Viability loss under all conditions used in this study was correlated with decreases in cellular ATP. CONCLUSIONS: Comparisons of incubations performed under the two oxygenation conditions revealed that viability loss was inversely associated with ROS production, which indicates that ATP loss and not ROS production was a better predictor of loss in cell integrity. This study also demonstrates that the level of dietary fat has only minor effects on generation of ROS and the cellular energy state. In contrast, ethanol consumption had significant effects on generation of ROS, energy state, and hepatocyte viability.     

Sensory Denervation Reduces Visceral Hypersensitivity in Adult Rats Exposed to Chronic Unpredictable Stress: Evidences of Neurogenic Inflammation

The purpose of this study is to provide evidence of neurogenic inflammation in chronic unpredictable stressed rats with the changes of visceral sensitivity, number of mast cells, and close proximity among mast cell-nerve-blood vessels. We found that (1) capsaicin denervation blocked stress-induced increase of visceral sensitivity, while doxantrazole presented a partial blocking; (2) capsaicin denervation blocked stress-induced enhancement of the proximity of mast cell-nerve fiber-blood vessels and blood vessel damage, while doxantrazole showed no effects on these; (3) doxantrazole blocked stress-induced increases of the MPO activity, the number and the degranulation of mast cells in the colon; (4) sensory denervation and doxantrazole had no effects on stress-induced behavioral inhibition. These results suggest that capsaicin-sensitive sensory fibers play a key role in stress-induced visceral hypersensitivity and the ultrastructural changes, mast cells play an important role in the generation of stress-induced colon inflammation.     

茶多酚对高脂饮食诱发大鼠非酒精性脂肪肝的防护作用以及对CYP 2E1表达的影响

目的:研究茶多酚对高脂饮食诱发大鼠非酒精性脂肪肝(NAFL)的防护作用以及对肝细胞色素P450 2E1(CYP 2E1)表达的影响,初步评价超声显像联合血脂、转氨酶检测对大鼠NAFL的诊断价值.方法:SD大鼠50只随机分为5组:正常对照组,茶多酚高、中、低剂量组(0.9g/kg、0.3g/kg、0.1g/kg)和模型组.除正常组外各组均给予高脂饮食.实验8周后,观察各组大鼠肝组织和血清MDA含量、SOD活性,肝组织GSH含量,肝功能酶学改变、脂质代谢、血清游离脂肪酸(FFA)水平,以及超声显像、病理组织学和CYP 2E1表达的特点.结果:茶多酚高、中、低剂量组大鼠血清SOD活性、MDA含量和FFA水平,以及肝组织SOD活性、MDA含量、GSH含量与模型组相比差异均有显著性意义(P＜0.05或P＜0.01),各用药组大鼠血脂水平与模型组相比也有明显差异(P＜0.05);组织学观察表明高、中剂量茶多酚均能明显减轻肝细胞脂肪变性(P＜0.05);肝脏超声显像证实造模成功以及用药能减轻肝脏脂肪变性程度,CYP 2E1的表达与肝细胞脂肪变性程度相一致.结论:茶多酚对大鼠NAFL具有良好的防护作用,并有一定的量效关系,超声显像联合血脂、转氨酶检测对NAFL有初步诊断价值.     

复合膳食纤维对高胆固醇血症大鼠胆固醇代谢的长期作用

健康、断乳SD大鼠 84只 ,经高脂饲料诱导形成高脂血症模型后按体重及血胆固醇均衡的原则分为 7组 ,分别以基础饲料及高脂饲料作为对照组 ,其余 5组饲以不同水平的复合膳食纤维配方B(可溶性纤维 不可溶性纤维 =2 .0 ) ,实验期为 3个月 ,观察配方B对大鼠血浆胆固醇代谢的长期作用。结果表明 :与高脂组相比 ,高胆固醇血症大鼠的血总胆固醇、低密度脂蛋白胆固醇在不同水平的复合膳食纤维配方B组均显著降低 (P <0 .0 5 ) ,而高密度脂蛋白胆固醇水平及高密度脂蛋白胆固醇 低密度脂蛋白胆固醇比值显著升高 (P <0 .0 5 ) ;复合膳食纤维配方B在降低大鼠血总胆固醇浓度的作用上 ,存在明显的剂量反应关系。以上结果提示 :以燕麦麸、沙棘皮、瓜儿豆胶为主要原料研制成的复合膳食纤维确能长期有效地降低血浆胆固醇水平 ,可用于动脉粥样硬化和冠心病的防治。     

Effect of early preoperative 5-fluorouracil on the integrity of colonic anastomoses in rats

AIM： To determine the effect of chemotherapy on wound healing by giving early preoperative 5-fluorouracil （5-FU） to rats with colonic anastomoses.METHODS： Sixty Albino-Wistar male rats （median weight, 235 g） were used in this study. The rots were fed with standard laboratory food and given tap water ad libitum. The animals were divided into three groups： Group 1： Control group （chemotherapy was not administered）, Group 2： Intraperitoneally （IP） administered 5-FU group （chemotherapy was administered IP to animals at a dose of 20 mg/kg daily during the 5 d preceeding surgery）, Group 3： Intravenously （IV） administered 5-FU group. Chemotherapy was administered v/a the penil vein, using the same dosing scheme and duration as the second group. After a 3-d rest to minimize the side effects of chemotherapy, both groups underwent surgery. One centimeter of colon was resected 2 cm proximally from the peritoneal reflection, then sutured intermittently and subsequently end-to-end anastomosed. In each group, half the animals were given anaesthesia on the 3rd postoperative （PO） day and the other half on the 7th PO day, for in vivo analytic procedures. The abdominal incisions in the rats were dissected, all the new and old anastomotic segments were clearly seen and bursting pressures of each anastomotic segment, tissue hydroxyproline levels and DNA content were determined to assess the histologic tissue repair process. RESULTS： When the IV group was compared with the IP group, bursting pressures of the anastomotic segments on the 3rd and 7th PO days, were found to be significantly decreased, hydroxyproline levels at the anastomotic segment on the 7th PO day were significantly decreased （P 〈 0.01）. CONCLUSION： In this study, we conclude that early preoperative 5-FU, administered IV, negatively affects wound healing. However, IP administered 5-FU does not negatively affect wound healing.