皮质抑素调控钙化相关基因减轻大鼠动脉钙化

目的 探讨皮质抑素（cortistatin，CST）对大鼠主动脉钙化的影响及其可能的分子机制。方法 利用维生素D3联合尼古丁（VDN）所致的大鼠动脉钙化模型，分别采用孔雀绿直接显色法、邻甲酚酞络合酮比色法和von Kossa染色法测定大鼠血浆磷、钙水平和主动脉组织的钙含量和钙沉积，应用RT-PCR方法检测主动脉组织钙化相关基因mRNA表达。结果 与对照组相比较，VDN使大鼠主动脉的钙含量增加70.2%（P<0.05），引起弹力纤维紊乱、中断，von Kossa染色阳性的棕黑色颗粒明显增多。VDN+CST组与单独VDN组相比较，持续皮下泵入CST使主动脉的钙含量减少45.6%（P<0.05），弹力纤维紊乱中断减轻和棕黑色颗粒明显减少。而血钙、磷及钙磷乘积在各组间无显著性差异。RT-PCR结果证实VDN组主动脉组织的BMP-2 mRNA和Pit-1 mRNA表达分别增加53.2%（P<0.05）和34.0%（P<0.01），而MGP mRNA表达减少27.0%（P<0.05）。持续皮下泵入CST使主动脉组织BMP-2 mRNA和Pit-1 mRNA表达较单独VDN组分别下降38.3%（P<0.01）和17.4%（P<0.05），而MGP mRNA表达增加34.9%（P<0.01）。主动脉组织OPG mRNA表达在各组间均无显著性差异。结论 CST能够减轻VDN所致的大鼠动脉钙化，可能与其纠正促\抑钙化相关基因表达失衡有关，从而为CST防治动脉钙化提供实验依据。     

钙调神经磷酸酶对钙化细胞Ⅰ型三磷酸肌醇受体表达的影响

目的探讨大鼠血管平滑肌细胞钙化过程中钙调神经磷酸酶对Ⅰ型三磷酸肌醇受体蛋白和mRNA表达的影响。方法大鼠胸主动脉血管平滑肌细胞经传代培养后随机分为对照组、钙化组和环孢素A组,采用磷酸二氢钠诱导大鼠动脉血管平滑肌细胞钙化。应用免疫印迹法及实时荧光定量RT-PCR法测定钙调神经磷酸酶B亚基、Ⅰ型三磷酸肌醇受体的表达变化,同时测定Ca2+浓度及碱性磷酸酶、钙调神经磷酸酶活性。结果与对照组比较,钙化组钙调神经磷酸酶B亚基、Ⅰ型三磷酸肌醇受体蛋白和mRNA表达显著增加(P<0.01);与钙化组比较,环孢素A组钙调神经磷酸酶B亚基、Ⅰ型三磷酸肌醇受体蛋白和mRNA表达显著降低(P<0.01)。钙化组Ca2+浓度、钙调神经磷酸酶活性、碱性磷酸酶活性较对照组显著增高(P<0.01);环孢素A组碱性磷酸酶活性、Ca2+浓度较钙化组显著增加(P<0.05或P<0.01),钙调神经磷酸酶活性较钙化组显著降低(P<0.01)。结论钙调神经磷酸酶能够增强钙化细胞中Ⅰ型三磷酸肌醇受体mRNA和蛋白的表达。     

高钙血症加重大鼠血管钙化

目的探讨高钙血症对血管钙化的影响。方法用维生素D3加尼古丁诱导大鼠血管钙化模型,von Kossa染色、钙含量测定、45Ca2 聚集及碱性磷酸酶活性测定判断钙化程度,用竞争性半定量逆转录聚合酶链反应方法测定血管钙化标志分子骨桥蛋白和β-actin mRNA水平。结果钙化组大鼠血压升高,收缩压较对照组高28%(P<0.05);血管von Kossa染色见血管中膜弹性纤维间可见大量棕黑色颗粒沉积。主动脉钙含量、45Ca2 沉积及碱性磷酸酶活性分别较对照高3.7倍、1.3倍和1.4倍(P<0.01)。钙化血管组织骨桥蛋白mRNA表达上调46%(P<0.01)。与对照组比较,高钙摄入增加血钙而降低血磷水平(2.49±0.14比2.20±0.12;1.25±0.05比1.40±0.07,P<0.01),单纯高钙摄入组主动脉钙含量、45Ca2 沉积及碱性磷酸酶活性与对照组比较差异无显著性(P>0.05)。而诱导钙化后给予高钙饮食可增加血管钙化程度,与单纯钙化组比较,主动脉钙含量、45Ca2 沉积及碱性磷酸酶活性分别升高了12%(P>0.05)、38%(P<0.01)和15%(P<0.01);骨桥蛋白表达上调34%(P<0.01)。结论高钙摄入可以加重大鼠血管钙化。     

血管钙化模型大鼠salusin-α表达的实验研究

目的通过制作血管钙化模型大鼠,观察血浆和主动脉组织salusin-α的表达情况。方法将16只雄性SD大鼠随机分为正常组和钙化组,每组8只,4周后取材检测血管钙化程度,用钙离子测试盒、碱性磷酸酶(ALP)试剂盒测定大鼠主动脉钙含量和ALP活性,用放射免疫法检测大鼠血浆和主动脉组织salusin-α含量。结果与对照组比较,钙化组大鼠主动脉中膜弹性纤维间可见钙盐沉积,血浆和主动脉组织中ALP、钙含量明显升高(P0.01),salusin-α的表达明显降低(P0.01)。结论血管钙化大鼠模型salusin-α的表达下调。     

同型半胱氨酸对血管钙化的促进作用

目的 在体外血管钙化模型基础上探讨同型半胱氨酸（HCY）对血管钙化的影响。方法 建立牛主动脉平滑肌细胞体外钙化模型（钙化BASMCs)。检测HCY对细胞层钙含量。培养上清骨钙素浓度及碱性磷酸酶活性的影响。并检测骨钙素，骨桥蛋白及Ⅰ型胶原（ColⅠ)mRNA表达的变化及抗氧化剂N-乙酰半胱氨酸对HCY促钙化作用的影响。结果 HCY剂量依赖性促钙化BASMCs钙沉积，但不促进非钙化的BASMCs钙沉积；N-乙酰半胱氨酸抑制HCY对钙化BASMCs钙沉积的促进作用。但在钙化BASMCs中单纯加入等剂量的N-乙酰半胱氨酸对钙沉积无影响；HCY促钙化BASMCs培养上清骨钙素含量增加，且使骨桥蛋白，骨钙素，ColⅠmRNA表达分别增加56.33%,86.48%及110.64%。但对正常培养的BASMCs培养上清骨钙素含量及骨桥蛋白，骨钙素mRNA表达无影响。仅使ColⅠmRNA表达增加108.33%;HCY不影响正常及钙化BASMCs碱性磷酸酶活性。结论 （1）HCY是钙化的促进因子，而非启动因子；（2）HCY的促钙化作用可能部分是通过细胞外基质途径实现的；（3）N-乙酰半胱氨酸阻断HCY的促钙化作用。间接提示氧化反应参与此过程；（4）HCY的促钙化作用与碱性磷酸酶活性无关。     

大鼠血管钙化模型炎症因子及其受体的表达

目的观察血管钙化大鼠模型血清炎症因子[C反应蛋白（C-reactive protein,CRP）、白细胞介素-6（interleukin-6,IL-6）和单核细胞趋化蛋白-1（monocyte chemoattractant protein-1,MCP-1）]表达的变化,以及大鼠主动脉组织中与血清炎症因子相对应的受体表达的变化,以探讨炎症因子在血管钙化中的作用和意义。方法实验动物按电脑随机数字表法分为正常组和钙化组,每组8只,钙化组采用维生素D3（300 000 U/kg1次肌肉注射）和尼古丁（25 mg/kg溶于花生油中,早、晚各灌胃1次）诱导大鼠血管钙化模型,用Von Kossa染色检测血管钙化程度,用钙离子测试盒、碱性磷酸酶（alkaline phosphatase,ALP）试剂盒测定大鼠主动脉钙含量和ALP活性,用放射免疫法检测大鼠血清炎症因子含量,用免疫组织化学法检测血管组织炎症因子受体表达。结果Von Kossa染色可见血管钙化模型大鼠主动脉有大量黑色颗粒沉淀。钙化组血管钙含量、ALP活性明显高于正常组,差异有统计学意义[分别为（0.42±0.05）μmol/g蛋白vs.（0.23±0.02）μmol/g蛋白,P〈0.01;（170.70±14.04）U/g蛋白vs.（110.30±14.05）U/g蛋白,P〈0.01]。钙化组血清炎症因子（CRP、IL-6和MCP-1）的表达比正常组明显上调,差异有统计学意义[分别为（2.20±0.14）mg/L vs.（1.69±0.24）mg/L,P〈0.01;（182.80±4.48）ng/L vs.（153.10±4.28）ng/L,P〈0.01;（83.07±2.37）ng/L vs.（70.52±2.12）ng/L,P〈0.01]。与正常组相比,血管钙化模型大鼠主动脉组织中的炎症因子相应受体（IL-6受体和MCP-1受体）的表达亦同步上调。结论钙化大鼠血清炎症因子和主动脉相应受体表达上调,提示炎症因子参与血管钙化的发生和发展过程。     

血管紧张素Ⅱ对正常和高血压大鼠主动脉平滑肌细胞腺苷三磷酸酶的影响

目的 探讨血管紧张素Ⅱ对正常血压Wistar-Kyoto大鼠和自发性高血压大鼠胸主动脉平滑肌细胞膜腺苷三磷酸酶(Ca2+-ATPase和Na+,K+-ATPase)活性及基因表达的影响.方法 组织块种植法培养14周龄Wistar-Kyoto大鼠和自发性高血压大鼠胸主动脉平滑肌细胞,分别加入含有1×10-9、1×10-8和1×10-7 mol/L血管紧张素Ⅱ培养液,共同孵育6 h、12 h和24 h.采用生化酶学方法和逆转录聚合酶链反应技术,检测主动脉平滑肌细胞膜Ca2+-ATPase、Na+,K+-ATPase活性及其mRNA表达水平.结果 低、中浓度血管紧张素Ⅱ(1×10-9和1×10-8 mol/L ) 增加Wistar-Kyoto大鼠 Ca2+-ATPase活性(P<0.05~P<0.01),与干预时间呈正相关(r=0.340, 0.725),24 h达最大值,且上调质膜Ca2+-ATPase 亚型1 mRNA表达 (P<0.05~P<0.01);高浓度 (1×10-7mol/L ) 血管紧张素Ⅱ抑制Ca2+-ATPas活性(P<0.05),与干预时间呈负相关(r=-0.348 ),其24 h效应最强,并下调质膜Ca2+-ATPase 亚型1 mRNA表达 (P<0.05).3种浓度血管紧张素Ⅱ均抑制自发性高血压大鼠 Ca2+-ATPase活性(P<0.05~P<0.01),与干预时间呈负相关 (r=-0.346,-0.493,-0.759),24 h抑制最强,并下调质膜Ca2+-ATPase 亚型1 mRNA表达 (P<0.05~ P<0.01).3种浓度(1×10-9、1×10-8和1×10-7 mol/L )血管紧张素Ⅱ依次在24 h、12 h、6 h显著增加Wistar-Kyoto大鼠Na+,K+-ATPase 活性 (P<0.05~P<0.01),且剂量依赖性增加24 h Na+,K+-ATPase活性及上调α1亚单位mRNA 表达 (P<0.05~P<0.01),与干预时间呈正相关(r=0.425,0.645,0.767 ).低、中浓度血管紧张素Ⅱ对自发性高血压大鼠Na+,K+-ATPase活性及α1亚单位mRNA 表达均无影响 (均P>0.05);高浓度血管紧张素Ⅱ则抑制Na+,K+-ATPase活性(P<0.01),与干预时间呈负相关(r=-0.589),24 h达最大效应,且下调α1亚单位mRNA 表达(P<0.05).结论 血管紧张素Ⅱ对正常血压大鼠主动脉平滑肌细胞膜Ca2+-ATPase活性及质膜Ca2+-ATPase 亚型1 mRNA表达有双向作用,并呈剂量依赖性激活Na+,K+-ATPase活性及α1亚单位mRNA表达;抑制高血压大鼠主动脉平滑肌细胞膜Ca2+-ATPase、Na+,K+-ATPase活性及Ca2+-ATPase亚型1、α1亚单位 mRNA表达.     

β-磷酸甘油诱导体外培养大鼠主动脉平滑肌细胞的钙化

目的:研究β磷酸甘油对体外培养的大鼠主动脉平滑肌细胞的钙化作用。方法:采用组织块培养法体外培养大鼠主动脉平滑肌细胞。细胞分为钙化组和正常组。钙化组加入10mmol/Lβ磷酸甘油,0.1μmol/L胰岛素及50μg/L维生素C（钙化培养基）诱导细胞钙化,继续培养14d。茜素红S染色观察钙结节计数并测定细胞钙沉积含量。采用四唑盐比色法（MTT）测量细胞增殖。结果:钙化组钙结节计数为（7.4±3.8）%,较正常组（4.3±1.9）%显著增加（P<0.05）;细胞钙沉积含量为（5.4±0.4）mmol/g蛋白,较正常组（1.2±0.5）mmol/g蛋白显著增加（P<0.05）。MTT检测细胞增殖,钙化组细胞增殖为0.071±0.011,较正常组0.040±0.009明显增加（P<0.01）。结论:β磷酸甘油能诱导体外培养的大鼠主动脉平滑肌细胞的钙化,钙化能促进平滑肌细胞的增殖。     

TGF-β对动脉钙化的影响

目的 :探讨转化生长因子 - β（TGF- β）在动脉钙化中的作用。方法 :建立体外动脉钙化的模型 ,培养钙化血管平滑肌细胞 ,在培养液中加入 TGF- β,观察钙沉积及细胞碱性磷酸酶的变化 ,同时观察钙化过程中骨间质蛋白骨钙素分泌情况。结果 :1μg/ L 的 TGF- β作用 10 d后 ,钙化细胞的钙沉积为 1.95± 0 .5 6 μm ol/ L,较钙化对照组 （1.71±0 .0 5 μm ol/ L）增加了 14.4% ,细胞碱性磷酸酶的活性为 5 46± 118IU/ L,比钙化对照组 （16 5± 6 3IU/ L）增加了2 95 % ,这种作用在第 8天达到高峰 ,以后略有下降。在钙化加重的同时 ,骨钙素分泌亦明显增加 ,达 0 .37± 0 .0 4ng/ L;而 TGF- β对非钙化的细胞无上述作用。结论 :1μg/ L 的 TGF- β可以促进钙化血管平滑肌细胞的钙化过程。     

麝香保心丸对实验大鼠血管钙化的作用

目的在大鼠血管钙化模型上,探讨麝香保心丸对血管钙化的影响及其可能作用机制。方法实验动物随机分正常组、钙化组及钙化+麝香保心丸组,每组6只。钙化组采用维生素D3(3×105U/kg 1次,肌肉注射)和尼古丁(25 mg/kg溶于花生油中,早、晚各灌胃1次)诱导大鼠血管钙化模型,钙化+麝香保心丸组于造模后第2天开始,每天麝香保心丸灌胃[14.0 mg/(kg·d)],用Von Kossa染色检测血管钙化程度,用钙离子测试盒、碱性磷酸酶(ALP)试剂盒测定大鼠主动脉钙含量和ALP活性,用放射免疫法检测大鼠血浆单核细胞趋化蛋白-1(MCP-1)含量,用免疫组织化学法检测血管组织MCP-1受体表达。结果维生素D3和尼古丁能够诱导典型大鼠血管钙化模型,Von Kossa染色可见血管钙化模型大鼠主动脉有大量黑色颗粒沉淀,钙化组血管钙含量、ALP活性高于正常组(P0.01),同时,血浆MCP浓度、血管组织MCP-1及其受体表达明显上调(P0.01);用麝香保心丸干预后,血管钙化程度减轻(P0.01)。血浆MCP-1及其受体的表达下调,差异有统计学意义。结论麝香保心丸可抑制血管钙化,并且提示可能通过下调MCP-1表达和ALP活性抑制血管钙化的发生和发展过程。     

Regression of warfarin-induced medial elastocalcinosis by high intake of vitamin K in rats

Arterial calcification (AC) is generally regarded as an independent risk factor for cardiovascular morbidity and mortality. Matrix Gla protein (MGP) is a potent inhibitor of AC, and its activity depends on vitamin K (VK). In rats, inactivation of MGP by treatment with the vitamin K antagonist warfarin leads to rapid calcification of the arteries. Here, we investigated whether preformed AC can be regressed by a VK-rich diet. Rats received a calcification-inducing diet containing both VK and warfarin (W&K). During a second 6-week period, animals were randomly assigned to receive either W&K (3.0 mg/g and 1.5 mg/g, subsequently), a diet containing a normal (5 microg/g) or high (100 microg/g) amount of VK (either K1 or K2). Increased aortic calcium concentration was observed in the group that continued to receive W&K and also in the group changed to the normal dose of VK and AC progressed. Both the VK-rich diets decreased the arterial calcium content by some 50%. In addition, arterial distensibility was restored by the VK-rich diet. Using MGP antibodies, local VK deficiency was demonstrated at sites of calcification. This is the first study in rats demonstrating that AC and the resulting decreased arterial distensibility are reversible by high-VK intake.     

糖尿病大鼠钙化血管中Msx2和Wnt3a的表达

目的 研究糖尿病对血管钙化的影响及Msx2和wnt3a基因在钙化血管中的表达变化.方法 将48只雄性wistar大鼠随机分为四组:维生素D3和尼古丁诱导的单纯血管钙化组(n=12)、链脲佐菌素诱导的单纯糖尿病组(n=12)、链脲佐菌素联合维生素D3和尼古丁诱导的糖尿病合并血管钙化组(n=12)和正常雄性Wistar大鼠为正常对照组(n=12).测定大鼠血糖、血清胰岛素、总胆固醇和甘油三酯水平,以血管von Kossa染色、血管钙含量和碱性磷酸酶活性作为判断血管钙化程度的指标,测定大鼠血管中Msx2和wnt3a mRNA 的表达.结果 与正常对照组相比,单纯血管钙化组大鼠血管中Msx2和wnt3a mRNA 相对表达量有所升高(P<0.05),但血管钙含量和碱性磷酸酶活性无明显变化.与正常对照组及单纯血管钙化组相比,糖尿病合并血管钙化组大鼠的血管中,可见沿中膜弹力层内广泛分布的钙盐沉积,大鼠血管中钙含量和碱性磷酸酶活性以及血管内Msx2和wnt3amRNA 相对表达量明显增高(P<0.05).结论 糖尿病可以明显加速血管钙化的发生和发展.在糖尿病大鼠钙化血管中,骨形成过程中的转录因子Msx2和Wnt3a表达增高,提示血管钙化是一个类似于骨形成的过程,Msx2和Wnt3a 参与血管钙化病变的发生.     

基质金属蛋白酶9在大鼠单纯收缩期高血压模型发生中的作用

目的 研究基质金属蛋白酶9（MMP-9）在单纯收缩期高血压形成中的作用.方法 选用8周龄Wistar 雄性大鼠20只作为研究对象,随机分成两组,模型组（n=10）和对照组（n=10）.应用华法林和维生素K1诱导动脉中层钙化,8周后右侧颈动脉插管进行有创血压和心室内压力的检测.以及取材主动脉,Von Kossa染色分析动脉钙化程度;采用原子吸收光谱法测定血管组织中钙含量.采用弹性纤维染色法观察主动脉组织中弹性纤维形状;应用免疫组织化学和Western blot检测主动脉组织中MMP-9的表达水平.结果 模型组大鼠血压与对照组相比明显增高[收缩压：（ 151±9） vs （113±7） mmHg,P＜0.01,舒张压：（122±10） vs （98±8） mmHg,P＜0.05];而各组间平均左室内压无明显变化.模型组大鼠血压变化的同时伴有动脉形态结构的改变,主动脉和颈动脉中层钙化明显,模型组主动脉钙含量明显高于对照组[（17.9±1.8）vs（5.8±0.6）mg/g,P＜0.01].弹力纤维断裂变直,失去波浪形状.Western免疫印迹法分析模型组MMP-9蛋白表达较对照组明显升高.结论 利用华法林和维生素K1诱导的单纯收缩期高血压大鼠是可重复性好,便捷,以及与人体衰老相似较为理想的模型.MMP-9酶表达明显增多可促使大动脉中层弹力蛋白降解和钙在弹力纤维薄层的沉积,从而在单纯收缩期高血压形成中发挥着一定作用.     

阿伦膦酸钠在大鼠动脉钙化中的作用

目的研究阿伦膦酸钠(AL)对在体和离体大鼠动脉钙化的影响。方法4周龄SD雄性大鼠18只随机分为AL组、钙化组和正常组,前2组分别给予皮下注射华法林15mg.100g-1.12h-1,4d;维生素D3300000U.kg-1.24h-1,3d,以制备大鼠动脉钙化。AL组在钙化模型制备之前4d给予AL1mg.kg-1.24h-1皮下注射。细胞分为AL10-9、10-7和10-5mol/L组,钙化组和正常组。结果AL组大鼠主动脉vonKossa染色黑色深染结构减少。AL治疗的各组茜素红S染色发现钙结节计数较钙化组减少[(6.8±2.7,6.2±4.2,5.3±2.4)%比(7.4±3.8)%],细胞钙沉积含量减少[(5.2±1.2,4.8±1.7,3.5±1.8)%比(5.6±1.6)%],ALP活力和细胞增殖均降低,并呈剂量依赖性。结论AL能抑制大鼠动脉钙化。     

过氧化物酶体增殖物激活受体信号通路在大鼠高脂血症发生发展中的作用

目的 探讨过氧化物酶体增殖物激活受体(PPAR) γ/Caspase-8/Caspase-3信号通路在大鼠高脂血症发生发展中的作用.方法 将健康雄性SD大鼠60只〔4周龄,体质量(110±10)g〕随机分为正常对照组、高脂饮食组、叶酸组、维生索B12组、叶酸+维生素B12组.适应性喂养1周后,叶酸组、维生索B12组、叶酸+维生素B12组分别腹腔注射叶酸(0.5 mg/d)、维生素B12 (0.05 mg/d)、叶酸(0.5mg/d)+维生素B12(0.05 mg/d),同时给予高脂饲料喂养;对照组腹腔注射0.9％NaCl溶液(0.5 ml/d)同时给予正常饲料喂养;高脂饮食组给予高脂饲料喂养.第17周末取腹主动脉利用反转录-聚合酶链反应检测各组PPARγ、Caspase-8和Caspase-3 mRNA的表达.结果 叶酸组、叶酸+维生素B12组腹主动脉的PPARγ mRNA水平高于高脂饮食组;Caspase-8、Caspase-3mRNA水平低于高脂饮食组(P＜0.05),且叶酸+维生素B12组较叶酸组降低mRNA水平更明显(P＜0.05).结论 叶酸与维生素B12可以改善血管壁PPARγ、Caspase-8和Caspase-3 mRNA的水平从而防止高脂血症对血管内皮的损伤.     

Nutrient intake and diet quality in patients with systemic lupus erythematosus on a culturally sensitive cholesterol lowering dietary program

OBJECTIVE: To evaluate the effect of a culturally sensitive cholesterol lowering dietary program on energy, protein, fiber, vitamin and mineral intake, diet quality, and hemoglobin levels in patients with systemic lupus erythematosus (SLE). METHODS: Seventeen patients with SLE were randomized to a Step II diet intervention group or a control group for 12 weeks. The diet intervention was made up of weekly group sessions during the first 6 weeks followed by telephone counseling every 2 weeks for the last 6 weeks. Food intake was assessed by 3-day food record at baseline, 6, and 12 weeks. Diet quality was assessed by expressing the nutrients as a percentage of the Dietary Reference Intakes of the US National Academy of Sciences, or as a percentage of the nutrient guidelines by the National Cholesterol Education Program, Adult Treatment Panel III. Between- and within-group changes in nutrient intakes were assessed by repeated measures ANOVA. RESULTS: The changes in nutrient intakes were not significantly different between the groups for any of the nonfat nutrients except vitamin B12 (p = 0.05), which decreased in the diet group and increased in the control group. Within-group analysis showed a significant reduction (p = 0.0003 to 0.02) in the diet group in energy and sodium intake at 6 and 12 weeks and B12 intake at 12 weeks compared to the respective baseline values (28-32%, 37-41%, and 43%, respectively). Sodium intake decreased to 66-71% of the total sodium allowance (< 2400 mg per day) in the diet group. The intervention was successful in maintaining adequate intakes or even increasing intakes of most nutrients except B12, dietary fiber, folate, calcium, and iron, which were slightly higher or below 67% of the Dietary Reference Intakes or other dietary guidelines. Anemia, as assessed by hemoglobin levels, was present throughout the study and did not correlate with iron intake. CONCLUSION: This culturally sensitive cholesterol reducing diet program was successful in decreasing sodium intake and maintaining adequate intakes of most nutrients except B12, dietary fiber, iron, calcium, and folate. Future intervention studies in patients with SLE need to pay special attention to these nutrients and the presence of anemia.     

Increased serum levels of vitamin D and calcium in young men after replacement of butter with soft margarine in usual diet

Osteoporosis features include reduction of bone mass and increased predisposition to fractures. Osteoporosis is considered as one of frequent diseases developing in menopausal women and old men. The values of peak bone mass are the determinant of osteoporosis development. It is estimated that the peak bone mass is reached at the age between 16 and 30 years. (NIH Consensus, 2001). Insufficient intake of calcium and vitamin D in diet, with reduced sun exposure, low physical activity, low body weight are well documented risk factors for this disease in human. For that reason, in osteoporosis prevention it should be tried to ensure adequate supply of calcium in diet from early life, with adequate supply of vitamin D, as factors determining adequate mineralization of osseous tissue. The study was carried out for assessing changes of the levels of calcium and 25-OH cholecalciferol in serum replacing butter in usual diet with margarine enriched with vitamin D. After a period of diet stabilization the study group received first diet with butter, followed by diet with margarine in place of butter. Throughout the whole experiment the diet contained unchanged amounts of dairy products as a source of alimentary calcium. In the experiment 41 young healthy men aged 22.6 +/- 1.2 years participated. Every subject consumed in a period of 4 weeks 30 g of butter daily, and during the following 4 weeks margarine 30 g daily. Substitution of margarine for butter in usual diet raised 25-OH cholecalciferol level in serum by 5.56 ng/ml, that is 32.4% (p < 0.001), with consequent 0.12 mg (5%) rise of serum calcium level (p < 0.05). The intake of calcium with diet from dairy products was unchanged throughout the experiment 576-581 mg daily, that is 72% of the recommended intake. The obtained results suggest that independently of the amount of vitamin D intake with food and calcium with diet substitution of margarine enriched with vitamin D for butter was beneficial raising serum vitamin D level, and at the same time increasing calcium absorption from food. It can be accepted that the obtained results could support the opinion on beneficial effects of the consumption of high-quality margarine in daily diet as prevention of the development not only of atherosclerosis but also osteoporosis.     

普罗布考对高密度脂蛋白亚组分与抗氧化功能的影响

目的研究普罗布考对动脉粥样硬化(AS)兔HDL亚组分及氧化功能的影响,探讨普罗布考抗AS机制。方法选择18只新西兰大白兔随机分为:对照组6只,饲以普通饲料;AS组6只,饲以高脂饲料;普罗布考组6只,饲以高脂饲料基础上给予普罗布考400 mg/(kg·d)。1 2周后酶法检测血脂;分光光度计法检测血清对氧磷酶1(PON1)活性;采用化学沉淀法检测HDL_2/HDL;组织切片和HE染色检测主动脉内膜中层厚度(IMT)和动脉斑块/血管面积。结果实验12周后,与AS组比较,普罗布考组血清TC、LDL-C、HDL-C水平明显下降(P0.01);PON1活性明显升高(P=0.000);HDL_2/HDL明显降低(P=0.000),主动脉IMT明显减小(P=0.000),斑块面积/血管腔面积明显降低(P=0.002)。结论普罗布考通过提高PON1活性,降低HDL_2/HDL而改善HDL功能,减少主动脉IMT及斑块面积/血管腔面积,延缓AS进展。     

A pilot study with simvastatin and folic acid/vitamin B12 in preparation for the Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH)

BACKGROUND AND AIM: This study was conducted in preparation for the Study Evaluating Additional Reduction in Cholesterol and Homocysteine (SEARCH). SEARCH is a 12,000 patient 2X2 factorial study in post-myocardial infarction patients that will compare simvastatin 20 mg with simvastatin 80 mg to evaluate whether greater LDL-C reductions with simvastatin provide greater coronary event reductions. SEARCH will also test the hypothesis that lowering plasma homocysteine with folic acid and vitamin B12 will reduce coronary events. This pilot study was performed to determine whether any clinically meaningful interaction between simvastatin and folic acid/vitamin B12 exists. METHODS AND RESULTS: Following a 2-week diet/placebo run-in period, 141 patients with primary hypercholesterolaemia were randomised to one of three treatments for 6 weeks: 80 mg/day simvastatin and 2 mg folic acid/0.8 mg vitamin B12 daily (combination group); or 80 mg/day simvastatin and placebo vitamins (simvastatin alone group); or 2 mg folic acid/0.8 mg vitamin B12 daily and placebo simvastatin (vitamins alone group). The combination group and simvastatin alone group experienced similar serum lipid changes with reductions in LDL-cholesterol of 55.2% and 51.5% respectively. The combination group and vitamins alone group experienced similar homocysteine lowering with reductions in homocysteine of 25.3% and 23.1% respectively. All therapies were well tolerated. CONCLUSIONS: There was no detectable antagonistic effect when simvastatin and folic acid/vitamin B12 were administered concomitantly.