维生素对动脉粥样硬化危险因素损伤血管内皮的保护作用

目的：探讨4种维生素联合应用，对动脉粥样硬化危险因素损伤血管内皮是否具有保护作用。方法：24只雄性家兔被随机分成3组。对照组喂普通饲料，模型组在普通饲料中加人胆固醇、猪油和甲硫氨酸，维生素组饲料同模型组，每天再另外灌胃给予维生素E、C、B6和叶酸，连续8周。第8周末，取血检测相关指标。结果：与对照组相比，模型组血脂(除HDL-C以外)、同型半胱氨酸和内皮素水平均显著升高(t=2．412，P&;lt;0．05；t=3．802—5．830，P&;lt;0，01)，血清一氧化氮虽有降低，但在两组间没有显著差异；HDL-C／LDL-c比值明显减少(1=6．622 P&;lt;0．01)。与模型组比较，维生素组血清总胆固醇、LDL-C．同型半胱氨酸和血浆内皮素水平均显著降低(t=2．514—2．726，P&;lt;0．05)，而血清一氧化氮显著升高，HDL-C／LDL-C比值也明显增加(t=4．128～5．076，P&;lt;0．01)。结论：维生素E、C、B6和叶酸联合运用，能够降低血中多种危险因子的水平，调节血中内皮素和一氧化氮的平衡，减少或阻断危险因素对内皮功能的损伤，对血管内皮有保护作用。     

深海鱼油对高脂血症大鼠血脂的影响

[目的]探讨深海鱼油对高脂血症大鼠血脂的调节作用,为护理人员对高脂血症病人进行健康教育提供理论依据。[方法]应用Wistar雄性大鼠(n=36)饲喂高脂饲料4周造模成功,随机分成4组,低剂量组(0.21g/kg,n=10)和高剂量组(0.42g/kg,n=10)灌胃深海鱼油和饲喂高脂饲料,模型组(n=8)灌胃蒸馏水和饲喂高脂饲料,空白组(n=8)灌胃蒸馏水和饲喂基础饲料。试验30d,结束时测血清总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)和空腹血糖(FBG)。[结果]试验30d低、高剂量组TC、LDL-C、HDL-C显著低于模型组(P<0.05或P<0.01),TG、FBG与模型组差异无统计学意义(P>0.05),且HDL-C/TC(H/T)、HDL-C/LDL-C(H/L)也显著高于模型组(P<0.01)。[结论]深海鱼油具有降低总胆固醇和低密度脂蛋白胆固醇的作用。     

2型糖尿病合并非酒精性脂肪肝患者同型半胱氨酸及血脂特点分析

目的探讨在2型糖尿病(T2DM)合并非酒精性脂肪性肝病患者中检测空腹血清同型半胱氨酸(tHCY)的临床意义。方法将210例2型糖尿病患者分为不合并非酒精性脂肪性肝病组(A组)108例,合并非酒精性脂肪性肝病组(B组)102例,分别测定身高、体质量,抽空腹血检查同型半胱氨酸(tHCY)、总胆固醇(TC)、甘油三脂(TG)、高密度脂蛋白(HDL-C)及低密度脂蛋白(LDL-C)等,计算体质指数(BMI)。结果 B组的BMI、TG、TC、LDL-C及tHCY均明显高于A组(P<0.05)。而年龄,HDL-C明显小于A组(P<0.01),tHCY与BMI、TG、TC、LDL-C、HDL-C的相关分析:tHCY与TG﹙r=0.245,P<0.05﹚、BMI﹙r=0.216,P<0.05﹚、LDL-C﹙r=0.223,P<0.05﹚呈正相关,与HDL-C呈负相关﹙rs=-0.222,P<0.05﹚。结论血脂紊乱及血清同型半胱氨酸是T2DM合并非酒精性脂肪性肝病的危险因素,并且TG、BMI、HDL-C及LDL-C与血清同型半胱氨酸水平具有相关性。     

原发性高血压患者肱动脉内皮功能与致动脉粥样硬化危险因素的相关性

目的：观察原发性高血压患者血液内皮素、同型半胱氨酸、低密度脂蛋白胆固醇的水平,探讨这些危险因素之间相关性及相关程度,同时关注这些危险因素与超声心动图检测的反应性充血肱动脉内径变化率之间的关系.方法：①选择2003-10/2004-04在徐州医学院附属医院心内科住院的患者56例,男40例,女16例.所有病例依据血压水平分为2组：高血压组38例,男28例,女10例;血压正常组18例,男12例,女6例.其中高血压组据冠状动脉造影结果分为2组：单纯高血压组20例和高血压合并冠心病组18例.纳入对象均了解实验目的,并愿意配合.②测定患者血压,超声心动图测量肱动脉内皮功能.计算反应性充血肱动脉内径变化率[（血流介导的肱动脉内径-安静时肱动脉内径）/安静时肱动脉内径&;#215;100%],以反应性充血肱动脉内径变化率数值大小判断肱动脉内皮功能.采用免疫法测定患者血浆同型半胱氨酸水平,采用放射免疫学法测定患者血浆内皮素1水平,采用全自动生化仪测定患者血清低密度脂蛋白胆固醇水平.③计量资料差异比较采用t检验,数据间相关性分析采用直线相关分析,多因素相关分析采用Logistic回归分析.结果：高血压患者38例,血压正常患者18例均进入结果分析.①高血压组、高血压合并冠心病组、单纯高血压组患者血浆内皮素和同型半胱氨酸水平及血清低密度脂蛋白胆固醇明显高于血压正常组（P＜0.05～0.01）,而反应性充血肱动脉内径变化率明显低于血压正常组（P＜0.05～0.01）.单纯高血压组患者血浆内皮素和同型半胱氨酸水平明显低于高血压合并冠心病组（P＜0.01）,反应性充血肱动脉内径变化率明显高于高血压合并冠心病组（P＜0.01）.②高血压组患者血浆内皮素与同型半胱氨酸呈正相关（r=0.676,P＜0.01）;内皮素与反应性充血肱动脉内径变化率呈显著负相关（r=-0.636,P＜0.01）;同型半胱氨酸与低密度脂蛋白胆固醇、反应性充血肱动脉内径变化率呈显著负相关（r=-0.378,-0.591,P＜0.05,0.01）.内皮素与低密度脂蛋白胆固醇和反应性充血肱动脉内径变化率之间无相关性.③内皮素、同型半胱氨酸、低密度脂蛋白胆固醇是高血压致动脉粥样硬化的危险因素（OR=12.341,12.489,P=0.018,0.013）,高血压致动脉粥样硬化危险因素中以内皮素作用最强,其次是低密度脂蛋白胆固醇.结论：①高血压患者血浆中内皮素和同型半胱氨酸水平及血清低密度脂蛋白胆固醇水平明显异常,内皮功能障碍,而高血压合并冠心病者上述损害更为明显.②内皮素与同型半胱氨酸最终通过共同途径损伤血管内皮细胞,内皮功能失调,反应性充血肱动脉内径变化率下降.内皮素与低密度脂蛋白胆固醇是动脉粥样硬化的两个独立的危险因素.     

精神分裂症伴高同型半胱氨酸血症患者治疗前后尿酸与糖脂代谢变化的研究

目的探讨精神分裂症伴高同型半胱氨酸血症患者治疗前后血清三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、空腹血糖(FBG)、尿酸(UA)水平的变化。方法采用回顾性分析方法进行研究,收集2017年5月至2019年6月在该院就诊的106例精神分裂症患者的临床资料。根据同型半胱氨酸(HCY)检测结果将63例高同型半胱氨酸血症患者纳入高HCY组,43例HCY水平正常患者纳入正常HCY组,观察并比较两组患者治疗前后HCY、TG、HDL-C、LDL-C、FBG、UA的检测结果变化情况,探讨HCY与其他指标间的相关性。结果正常HCY组治疗后TG水平明显升高,高HCY组TG水平较治疗前明显升高,FBG及UA水平明显降低,差异均有统计学意义(P<0.05);治疗前血清HCY与UA呈正相关(r=0.408,P<0.001),与FBG、TG、HDL-C及LDL-C无相关性,治疗后血清HCY水平与UA和TG均呈正相关(r=0.342,P<0.01;r=0.212,P=0.046),与HDL-C呈负相关,与FBG和LDL-C无相关性(r=-0.280,P=0.004)。结论精神分裂症伴高同型半胱氨酸血症患者血脂代谢紊乱程度高于HCY正常的患者,所有患者治疗后血脂水平均升高;血清HCY与血清TG、UA和HDL-C水平间存在相关性。     

原发性高血压患者肱动脉内皮功能与致动脉粥样硬化危险因素的相关性

目的：观察原发性高血压患者血液内皮素、同型半胱氨酸、低密度脂蛋白胆固醇的水平，探讨这些危险因素之间相关性及相关程度，同时关注这些危险因素与超声心动图检测的反应性充血肱动脉内径变化率之间的关系。 方法：①选择2003-10／2004-04在徐州医学院附属医院心内科住院的患者56例，男40例，女16例。所有病例依据血压水平分为2组：高血压组38例，男28例，女10例；血压正常组18例，男12例，女6例。其中高血压组据冠状动脉造影结果分为2组：单纯高血压组20例和高血压合并冠心病组18例。纳入对象均了解实验目的，并愿意配合。②测定患者血压，超声心动图测量肱动脉内皮功能。计算反应性充血肱动脉内径变化率[(血流介导的肱动脉内径-安静时肱动脉内径)／安静时肱动脉内径×100％]，以反应性充血肱动脉内径变化率数值大小判断肱动脉内皮功能。采用免疫法测定患者血浆同型半胱氨酸水平，采用放射免疫学法测定患者血浆内皮素1水平，采用全自动生化仪测定患者血清低密度脂蛋白胆固醇水平。③计量资料差异比较采用t检验，数据间相关性分析采用直线相关分析，多因素相关分析采用Logistic回归分析。 结果：高血压患者38例，血压正常患者18例均进入结果分析。①高血压组、高血压合并冠心病组、单纯高血压组患者血浆内皮素和同型半胱氨酸水平及血清低密度脂蛋白胆固醇明显高于血压正常组(P<0．05～0．01)，而反应性充血肱动脉内径变化率明显低于血压正常组(P<0．05～0．01)。单纯高血压组患者血浆内皮素和同型半胱氨酸水平明显低于高血压合并冠心病组(P<0．01)，反应性充血肱动脉内径变化率明显高于高血压合并冠心病组(P<0．01)。②高血压组患者血浆内皮素与同型半胱氨酸呈正相关(r=0．676，P<0．01)；内皮素与反应性充血肱动脉内径变化率呈显著负相关(r=-0．636，P<0．01)；同型半胱氨酸与低密度脂蛋白胆固醇、反应性充血肱动脉内径变化率呈显著负相关(r=-0．378，-0．591，P<0．05，0．01)。内皮素与低密度脂蛋白胆固醇和反应性充血肱动脉内径变化率之间无相关性。③内皮素、同型半胱氨酸、低密度脂蛋白胆固醇是高血压致动脉粥样硬化的危险因素(OR=12．341，12．489，P=0．018，0．013)，高血压致动脉粥样硬化危险因素中以内皮素作用最强，其次是低密度脂蛋白胆固醇。 结论：①高血压患者血浆中内皮素和同型半胱氨酸水平及血清低密度脂蛋白胆固醇水平明显异常，内皮功能障碍，而高血压合并冠心病者上述损害更为明显。②内皮素与同型半胱氨酸最终通过共同途径损伤血管内皮细胞，内皮功能失调，反应性充血肱动脉内径变化率下降。内皮素与低密度脂蛋白胆固醇是动脉粥样硬化的两个独立的危险因素。     

脑血管病患者高Hcy血症与叶酸和维生素B12的相关性研究

目的探讨脑血管病患者高同型半胱氨酸(Hcy)血症与叶酸、维生素B12之间的相关性。方法分别检测脑血管病患者和健康对照者血清Hcy、叶酸和维生素B12水平。结果脑血管病组血清Hcy水平显著高于对照组(P<0.01),其中脑梗塞组的血清Hcy水平明显高于脑出血组(P<0.01)。与之相反,脑血管病组的血清叶酸和维生素B12水平明显低于对照组(P<0.01)。相关分析结果显示,脑血管病组的血清叶酸和维生素B12水平与Hcy水平呈负相关(r1=-0.80,r2=-0.83)。结论高Hcy血症与叶酸、维生素B12之间存在负反馈的调节机制可能正是导致脑血管病发生的关键因素。     

2型糖尿病慢性并发症与血清同型半胱氨酸水平的关系

目的探讨2型糖尿病慢性并发症与血清同型半胱氨酸水平的关系。方法用化学发光法检测50例2型糖尿病患者及50例正常对照者血清半胱氨酸、叶酸和维生素B12水平。结果糖尿病有并发症组与健康对照组相比,血清同型半胱氨酸水平明显升高(P<0.01),糖尿病无并发症组较正常对照者相比,血清同型半胱氨酸水平明显升高(P<0.01)。高同型半胱氨酸血症组心脑血管并发症发生率较健康对照组明显升高(P<0.05),糖尿病组叶酸水平明显低于健康对照组(P<0.01),糖尿病两亚组相比,差异无统计学意义。糖尿病组和健康对照组叶酸水平与同型半胱氨酸水平呈负相关(糖尿病组r=-0.36,P=0.01;对照组r=-0.41,P=0.02)。维生素B12水平糖尿病组与健康对照组相比差异无统计学意义(P>0.05),糖尿病两亚组相比差异无统计学意义(P>0.05)。糖尿病组和健康对照组维生素B12水平与同型半胱氨酸水平均无明显相关性(糖尿病组r=-0.20,P=0.14对照组r=-0.31,P=0.18)。结论高同型半胱氨酸血症易诱发2型糖尿病患者慢性并发症的发生,早期给予叶酸及B族维生素可能对预防慢性并发症的发生有益。     

血清总胆固醇与高密度脂蛋白胆固醇比值作为冠心病危险标志的意义

目的分析冠心病(CHD)患者的血脂水平,探讨血清总胆固醇(TC)与高密度脂蛋白胆固醇(HDL-C)比值作为CHD危险标志的临床意义。方法测定295例CHD患者的血清TC、三酰甘油(TG)、HDL-C及低密度脂蛋白胆固醇(LDL-C)水平,并计算TC/HDL-C比值。结果依据《中国成人血脂异常防治指南》颁布的血脂水平合适范围,CHD患者血清TC、TG及LDLC高于合适范围百分率分别为32.20%、34.24%及37.63%,血清HDL-C低于合适范围百分率为39.32%。血清TC/HDL-C比值高于合适范围百分率为57.29%。血清TC/HDL-C比值异常率显著高于血清TC、TG、HDL-C及LDL-C(χ2=37.540、31.576、19.066、22.866,P0.01)。结论与任一单项血脂检测相比,血清TC/HDL-C比值作为CHD危险标志可能更有临床意义,临床血脂检测报告单应增加TC/HDL-C比值。     

沙芥预防大鼠高脂血症及对血管内皮功能影响研究

目的观察沙芥对高脂饮食大鼠有无预防高血脂的作用及对血管内皮功能的影响。方法 64只Wistar大鼠,随机分为空白对照组、高脂模型组、血脂康药物组和沙芥高、中、低浓度组,除空白对照组给予普通饲料外,其余各组均饲喂高脂饲料,同时血脂康组和沙芥组,分别以血脂康混悬液和高、中、低浓度沙芥灌胃,空白、模型组灌等容积蒸馏水,每天一次,连续8周后处死。检测大鼠血清的总胆固醇（TC）、三酰甘油（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）,血浆内皮素（ET）、一氧化氮（NO）、降钙素基因相关肽（CGRP）水平。结果高脂组大鼠较空白组TC、TG、LDL-C、ET显著升高,HDL-C、NO、CGRP水平显著降低,提示模型组高脂血症模型已形成,并存在血管内皮损伤。各沙芥组均较高脂模型组大鼠的TC显著降低;高浓度沙芥组较模型组大鼠的LDL-C、ET显著降低,NO显著升高;中浓度PCG组较模型组NO显著升高。结论沙芥对高脂饮食的大鼠有一定的预防高脂血症的作用,并有一定的保护血管内皮功能的作用。     

Atorvastatin reduces serum leptin concentration in hypercholesterolemic rabbits

BACKGROUND: Leptin may play an important role in the development of atherosclerosis. We evaluated the effect of atorvastatin on leptin secretion in vivo and in vitro. METHODS: Sixteen rabbits fed with high-cholesterol diet for 8 weeks were randomly divided into 2 groups: (1) high cholesterol diet for 6 weeks (n=8), and (2) the same cholesterol diet plus atorvastatin (2.5 mg/kg/day) for 6 weeks (n=8). A control group (n=5) was fed with normal diet for 14 weeks. Subcutaneous adipose was collected for RNA analysis. The direct effect of atorvastatin on leptin release was assayed in primary rabbit adipocytes. Leptin levels in serum and adipocytes culture supernatant were measured by ELISA. RT-PCR was used to evaluate leptin mRNA expressions in adipose and adipocytes. RESULTS: Compared with control group, rabbits fed with high cholesterol diet showed higher levels of serum total cholesterol, LDL cholesterol and leptin, all of which were significantly reduced by atorvastatin treatment. Leptin mRNA expression of adipose was significant lower in rabbits treated with atorvastatin than those fed with high cholesterol diet continuously (0.81+/-0.31 vs. 1.23+/-0.36, P<0.05). Atorvastatin dose-dependently inhibited leptin secretion and mRNA expression in cultured adipocytes. CONCLUSION: Atorvastatin can inhibit leptin release and mRNA expression, and reduces serum leptin level in hypercholesterolemic rabbits.     

辛伐他汀、氨氯地平对实验性兔动脉粥样硬化进程中NOS/NO系统的影响

目的探讨诱导型一氧化氮合酶(iNOS)-一氧化氮(NO)系统在动脉粥样硬化进程中的变化、相互关系及辛伐他汀、氨氯地平对动脉粥样硬化进程中iNOS-NO的影响。方法 24只家兔予以高胆固醇饮食8周,8周后随机分为三组(n=8),三组均停用高胆固醇饮食,改普通饮食8周;模型组不用干预,另外两组分别喂饲辛伐他汀及氨氯地平进行药物干预。另取8只家兔予以普通饮食16周作为对照组。结果与对照组比较,模型组血脂水平明显升高,血清NO含量明显降低,iNOS表达明显升高(P均<0.01)。与模型组比较辛伐他汀组血浆TC、TG、LDL-C、ox-LDL-C下降明显(P<0.01),HDL-C升高(P<0.01);血清NO含量明显升高(P<0.01),iNOS表达明显减少(P<0.05)。而氨氯地平组血脂水平与模型组比较无统计学差异(P>0.05);血清NO含量亦无统计学差异(P>0.05),但iNOS表达明显减少(P<0.05)。结论动脉粥样硬化进程中,辛伐他汀、氨氯地平均可以通过下调血红素加氧酶/NO系统而延缓动脉粥样硬化进程。     

Low density lipoprotein is protected from oxidation and the progression of atherosclerosis is slowed in cholesterol-fed rabbits by the antioxidant N,N''-diphenyl-phenylenediamine.

The oxidative modification of low density lipoprotein (LDL) may play an important role in atherosclerosis. We found that the antioxidant N,N'-diphenyl-1,4-phenylenediamine (DPPD) inhibits in vitro LDL oxidation at concentrations much lower than other reported antioxidants. To test whether DPPD could prevent atherosclerosis, New Zealand White rabbits were fed either a diet containing 0.5% cholesterol and 10% corn oil (control group) or the same diet also containing 1% DPPD (DPPD-fed group) for 10 wk. Plasma total cholesterol levels were not different between the two groups, but DPPD feeding increased the levels of triglyceride (73%, P = 0.007) and HDL cholesterol (26%, P = 0.045). Lipoproteins from DPPD-fed rabbits contained DPPD and were much more resistant to oxidation than control lipoproteins. After 10 wk, the DPPD-fed animals had less severe atherosclerosis than did the control animals: thoracic aorta lesion area was decreased by 71% (P = 0.0007), and aortic cholesterol content was decreased by 51% (P = 0.007). Although DPPD cannot be given to humans because it is a mutagen, our results indicate that orally active antioxidants can have antiatherosclerotic activity. This strongly supports the theory that oxidized LDL plays an important role in the pathogenesis of atherosclerosis.     

Mildly oxidized LDL induces an increased apolipoprotein J/paraoxonase ratio.

We have examined the effects of mildly oxidized LDL and atherosclerosis on the levels of two proteins associated with HDL; apolipoprotein J (apoJ), and paraoxonase (PON). On an atherogenic diet, PON activity decreased by 52%, and apoJ levels increased 2.8-fold in fatty streak susceptible mice, C57BL/6J (BL/6), but not in fatty streak resistant mice, C3H/HeJ (C3H). Plasma PON activity was also significantly decreased, and apoJ levels were markedly increased in apolipoprotein E knockout mice on the chow diet, resulting in a 9.2-fold increase in the apoJ/PON ratio as compared to controls. Furthermore, a dramatic increase in the apoJ/PON ratio (over 100-fold) was observed in LDL receptor knockout mice when they were fed a 0.15%-cholesterol-enriched diet. Injection of mildly oxidized LDL (but not native LDL) into BL/6 mice (but not in C3H mice) on a chow diet resulted in a 59% decrease in PON activity (P < 0.01) and a 3.6-fold increase in apoJ levels (P < 0.01). When an acute phase reaction was induced in rabbits, or the rabbits were placed on an atherogenic diet, hepatic mRNA for apoJ was increased by 2.7-fold and 2.8-fold, respectively. Treatment of HepG2 cells in culture with mildly oxidized LDL (but not native LDL) resulted in reduced mRNA levels for PON (3.0-fold decrease) and increased mRNA levels for apoJ (2.0-fold increase). In normolipidemic patients with angiographically documented coronary artery disease who did not have diabetes and were not on lipid-lowering medication (n = 14), the total cholesterol/HDL cholesterol ratio was 3.1+/-0.9 as compared to 2.9+/-0.4 in the controls (n = 19). This difference was not statistically significant. In contrast, the apoJ/PON ratio was 3.0+/-0.4 in the patients compared to 0.72+/-0.2 in the controls (P < 0.009). In a subset of these normolipidemic patients (n = 5), the PON activity was low (48+/-6.6 versus 98+/-17 U/ml for controls; P < 0.009), despite similar normal HDL levels, and the HDL from these patients failed to protect against LDL oxidation in co-cultures of human artery wall cells. We conclude that: (a) mildly oxidized LDL can induce an increased apoJ/PON ratio, and (b) the apoJ/PON ratio may prove to be a better predictor of atherosclerosis than the total cholesterol/HDL cholesterol ratio.     

Ameliorative effect of statin therapy on oxidative damage in heart tissue of hypercholesterolemic rabbits

The aim of this study was to investigate the effects of a high‐cholesterol diet in the presence and absence of statin on Cu‐Zn‐superoxide dismutase (Cu,Zn‐SOD), malondialdehyde (MDA), protein carbonyl (PCO), and nitric oxide (NO) of blood and heart tissue, the antioxidant activity of serum paraoxonase‐1 (PON‐1), and on the blood lipid profile of rabbits. The animals were divided into four groups each of which included 10 rabbits. Rabbits in group 1 received a regular rabbit chow diet (normal diet) for 8 weeks; those in group 2 received atorvastatin (0.3 mg atorvastatin per day/kg body weight) for 8 weeks; those in group 3 received high‐cholesterol diet for 8 weeks; and those in group 4 received high‐cholesterol diet for 4 weeks, a high‐cholesterol diet + atorvastatin (0.3 mg atorvastatin per day/kg body weight) for 8 weeks. The parameters were measured by spectrophotometric methods. As expected, the atherogenic diet caused a pronounced increase in lipid profile (not HDL) parameters. Rabbits in group 3 showed higher PCO, MDA, and NO levels in circulating and heart tissue compared to the rabbits in group 1. Atorvastatin has prevented or limited LDL oxidation and has showed constitutively beneficial effects in group 4. Increased LDL‐C, PCO, MDA, and NO levels leading to decreasing PON‐1 activity thus create a predisposition to atherogenesis in this model. But atorvastatin administration partly ameliorated oxidative damage in heart injury of hypercholesterolemic rabbits. Atorvastatin which functions as a potent antioxidant agent may inhibit this LDL‐C oxidation by increasing PON‐1 activity in atherogenesis.     

Increased levels of high-density lipoprotein cholesterol are ineffective in inhibiting the development of immune responses to oxidized low-density lipoprotein and atherosclerosis in transgenic rabbits expressing human apolipoprotein (apo) A-I with severe hypercholesterolaemia

High levels of high-density lipoprotein (HDL) cholesterol have been reported to protect against the development of atherosclerosis in humans by increasing reverse cholesterol transport and inhibiting the oxidation of low-density lipoprotein (LDL) due to the paraoxonase content of HDL. The purpose of the present study was to assess if there are any relationships between in vivo increases in serum levels of immunological LDL oxidation markers [autoantibodies against oxidized LDL, autoantibodies against malondialdehyde-modified LDL, LDL immune complexes and anti-cardiolipin autoantibodies], paraoxonase activity and the development of atherosclerosis in control rabbits and in transgenic rabbits expressing human apolipoprotein (apo) A-I. A total of 13 apo A-I transgenic rabbits and 18 non-transgenic littermates were fed on a cholesterol-rich diet (0.4%, w/w) for 14 weeks, and were monitored at weeks 0, 2, 6, 10 and 14. Aortic atherosclerotic lesions were measured at the end of this period. Human apo A-I transgenic rabbits with high HDL cholesterol levels were not protected against the development of atherosclerosis when they were fed on a cholesterol-rich diet which induced dramatic hypercholesterolaemia. Immunological markers of LDL oxidation increased and serum paraoxonase activity decreased similarly in control and transgenic rabbits. In conclusion, the present study demonstrates that high HDL cholesterol levels are ineffective in inhibiting increases in immunological markers of LDL oxidation and the development of atherosclerosis in a mammal with severe hypercholesterolaemia.     

Pistachio intake increases high density lipoprotein levels and inhibits low-density lipoprotein oxidation in rats

There is increasing evidence that nuts have protective effects against coronary artery disease by improving lipid profile and inhibiting lipid oxidation. However, data about pistachio nuts are limited, and to our knowledge, there is no study investigating the effects of pistachio intake on lipid oxidation and serum antioxidant levels. This study, therefore, sought to determine the effects of pistachio intake on serum lipids and determine whether consumption of pistachio would alter serum antioxidant levels. Rats were randomly divided into three groups (n=12 for each): control group fed basic diet for 10 weeks and treated groups fed basic diet plus pistachio which constituted 20% and 40% of daily caloric intake, respectively. Consumption of pistachio as 20% of daily caloric intake increased high-density lipoprotein (HDL) levels and decreased total cholesterol (TC)/HDL ratio, compared with those not taking pistachio. However, TC, low-density lipoprotein (LDL) cholesterol and triglyceride levels were unaffected by pistachio consumption. Consumption of pistachio as 20% of daily caloric intake increased serum paraoxonase activity by 35% and arylesterase activity by 60%, which are known to inhibit LDL cholesterol oxidation, compared with the control group. However, increased antioxidant activity was blunted when pistachio intake was increased to 40% of daily caloric intake. In conclusion, the present results show that consumption of pistachio as 20% of daily caloric intake leads to significant improvement in HDL and TC/HDL ratio and inhibits LDL cholesterol oxidation. These results suggest that pistachio may be beneficial for both prevention and treatment of coronary artery disease.     

The effect of acetaminophen on oxidative modification of low-density lipoproteins in hypercholesterolemic rabbits

Oxidative modification of low-density lipoproteins (LDL) contributes to the pathology of atherosclerosis. Antioxidants may protect LDL against oxidative modification. Acetaminophen, a widely used analgesic and antipyretic agent, has significant antioxidant properties. However, there is little evidence to suggest that acetaminophen acts as an antioxidant for LDL oxidation in vivo. In this study, we investigated the in vivo effect of acetaminophen on LDL oxidation in hypercholesterolemic rabbits. The oxidative modification of LDL was identified by conjugated dienes and thiobarbituric acid-reactive substances (TBARS). In the cholesterol group which rabbits were fed a diet contained 1% g cholesterol for 8 weeks, TBARS contents and conjugated diene levels in the plasma and isolated LDL samples significantly increased compared with the control rabbits (p<0.05). However, in the cholesterol + acetaminophen group, the TBARS contents and conjugated diene levels were significantly lower than that of the cholesterol group (p<0.05). The results from in vitro studies also demonstrated that the LDL isolated from serum was oxidized by Cu(++) ions and this oxidation reduced in the presence of acetaminophen. The reduced oxidative modification of LDL by acetaminophen may be of therapeutic value in preventing the development and progression of atherosclerosis.     

Comparison of the effects of vitamins and/or mineral supplementation on glomerular and tubular dysfunction in type 2 diabetes

OBJECTIVE: The present study was designed to assess the effect of magnesium plus zinc, vitamins C plus E, and a combination of these micronutrients on nephropathy indexes in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: In a randomized, double-blind, placebo-controlled clinical trial, 69 type 2 diabetic patients were randomly divided into four groups, each group receiving one of the following daily supplement for 3 months: group M (n = 16), 200 mg Mg and 30 mg Zn; group V (n = 18), 200 mg vitamin C and 100 IU vitamin E; group MV (n = 17), minerals plus vitamins; and group P (n = 18), placebo. Urinary albumin excretion and N-acetyl-beta-d-glucosaminidase activity (NAG) in urine were determined at the beginning and at the end of the trial. Treatment effects were analyzed by general linear modeling. RESULTS: Results indicate that after 3 months of supplementation, levels of urinary albumin excretion decreased in the V and MV groups (P = 0.034 and P = 0.005, respectively). Urinary NAG activity did not significantly change in any treatment groups. Levels of systolic, diastolic, and mean blood pressure significantly decreased in the MV group (P = 0.008, P = 0.017, and P = 0.009, respectively). Also, combination of vitamin and mineral supplementation had significant effects in decreasing fasting serum glucose (P = 0.035) and malondialdehyde concentrations (P = 0.004) and in increasing HDL cholesterol and apolipoprotein A1 levels (P = 0.019). There was no significant change in the levels of these parameters in the other three groups. CONCLUSIONS: In conclusion, the results of the present study provide evidence for the effects of vitamins C and E and also combination of magnesium, zinc, and vitamins C and E supplementation on improvement of glomerular but not tubular renal function in type 2 diabetic patients.