维生素B12和叶酸干预对绝经后骨质疏松症妇女的骨代谢及同型半胱氨酸水平的影响

目的观察叶酸和维生素B12对绝经后骨质疏松症妇女的骨代谢及同型半胱氨酸水平的影响。方法 80例绝经后骨质疏松症妇女参加研究。所有参与者随机接受叶酸和维生素B12(n=40)或安慰剂(n=40)治疗。在干预前的基线及干预后3个月和6个月,测量两组患者血清同型半胱氨酸、维生素B12和骨代谢标志物的水平。结果治疗前,两组患者血清同型半胱氨酸、维生素B12和骨代谢标志物水平比较差异无统计学意义(P0.05)。治疗后,两组患者同型半胱氨酸均下降,但比较差异无统计学意义(P0.05)。6个月后各组间血清维生素B12、骨钙素、CTX的变化均有显著改变且差异有统计学意义(P0.05)。结论绝经后骨质疏松症妇女补充叶酸和维生素B12可以一定程度改善同型半胱氨酸及骨代谢指标水平。     

同型半胱氨酸与绝经后女性颈动脉粥样硬化的相关性研究

目的 研究同型半胱氨酸(homocysteine,Hcy)是否为绝经后女性颈动脉粥样硬化的独立风险因素。 方法 对2017年12月—2018年12月北京协和医院健康体检的1 204名55岁以上绝经后女性,进行Hcy检测和颈动脉超声检查。使用多变量logistic回归方法分析Hcy及其他传统风险因素对颈动脉粥样硬化的影响。 结果 Hcy平均值(12.4±3.3)μmol/L,高Hcy血症176人(14.62%)。Hcy与年龄和BMI正相关(分别r=0.19,P<0.001;r=0.11, P<0.001)。颈动脉粥样硬化患者的Hcy显著升高(Z=-2.56,P=0.011)。logistic回归显示,对于颈动脉粥样硬化只有年龄(OR=1.11,95%CI:1.09~1.14)和收缩压(OR=1.02,95%CI:1.01~1.02)是独立风险因素;对颈动脉斑块形成年龄(OR=1.10,95%CI:1.08~1.12)、收缩压(OR=1.02,95%CI:1.01~1.03)、糖化血红蛋白(OR=1.27,95%CI:1.07~1.50)和高血压病史(OR=1.40,95%CI:1.06~1.87)是独立危险因素。 结论 在绝经后女性,Hcy不是动脉粥样硬化发生的独立风险因素,筛查高Hcy血症在预防该人群颈动脉粥样硬化的意义仍需进一步证明。     

ASSOCIATION OF PLASMA HOMOCYSTEINE LEVEL AND N^5,N^10—METHYLENETETRAHYDROFOLATE REDUCTASE GENE POLYMORPHISM WITH CEREBRAL INFARCTION

OBJECTIVE: To investigate the relationship of plasma homocysteine (Hcy) level to stroke and genetic factor to elevated plasma Hcy level. METHODS: The plasma Hcy level was measured by capillary electrophoresis-ultraviolet detection and the gene polymorphism of N5,N10-methylenetetrahydrofolate reductase (MTHFR) was studied with PCR-RFLP assay in 43 patients with cortical cerebral infarction and 42 healthy control. RESULTS: The plasma Hcy level of the patients (19.3 +/- 6.0 micromol/L) was markedly higher than that of the controls (13.7 +/- 5.4 micromol/L) (t = 4.16, P < 0.001). There are 3 genotypes, C/C, C/T and T/T, about base-variation of MTHFR gene at locus 677. The plasma Hcy level of the subjects with T/T genotype was higher than that of subjects with other genotypes. However, the frequencies of each genotype and allele were not significantly different between the patients and the controls. CONCLUSIONS: The elevated plasma Hcy level is a risk factor for atherothrombotic cerebral infarction, and is related to the C-->T mutation at locus 677 of MTHFR gene.     

窒息新生儿出生体重与血清同型半胱氨酸关系

目的探讨窒息新生儿出生体重对其血清中高同型半胱氨酸血症及低叶酸水平的关系。方法同期出生的新生儿分为正常组和窒息组,并分别分为正常体重及低体重组。应用酶联免疫吸附实验方法检测血清中Hcy水平。应用放射免疫法测定血中叶酸浓度。结果窒息组正常体重儿血清同型半胱氨酸为(10.50±2.19)μmol/L,低体重儿为(15.82±2.51)μmol/L,对照组正常体重儿血清同型半胱氨酸为(7.73±0.61)μmol/L,低体重儿为(7.45±0.43)μmol/L。在窒息组内低体重儿血清同型半胱氨酸水平明显高于正常体重儿(P<0.001),且窒息低体重组儿血清同型半胱氨酸水平明显高于正常对照组儿,不论其出生体重如何(P<0.001)。血清叶酸水平检测结果显示窒息组正常体重儿血清叶酸水平为(2.74±0.16)μg/L,低体重儿为(2.29±0.25)μg/L,对照组正常体重儿血清叶酸为(3.33±0.23)μg/L,低体重儿为(3.02±0.29)μg/L。窒息组患儿无论正常体重儿还是低体重儿其血清叶酸水平变化均不显著(P>0.05)。结论缺氧窒息合并低出生体重者血清同型半胱氨酸水平显著升高。     

高效液相色谱-荧光检测法测定血浆总同型半胱氨酸浓度

目的 :建立测定血浆总同型半胱氨酸的高效液相色谱 (HPLC) 荧光检测分析方法。方法 :用TCEP将血浆中各种形式的同型半胱氨酸 (Hcy)还原成总同型半胱氨酸 (tHcy) ,以光胺作内标 ,巯基特异性荧光衍生剂SBD F对Hcy ,胱胺等含巯基化合物进行柱前衍生 ,然后行HPLC 荧光检测。结果 :本方法所检测的Hcy浓度在 2 .5～ 16 0 μmol·L- 1 范围具有良好的线性关系 (r =0 .9975 ) ,Hcy最低检测限 0 .6 2 5 μmol·L- 1 ,批内变异小于 5 .5 % ,批间变异小于 9.0 % ,平均回收率 98.87%。结论 :本法简便、灵敏、精确、稳定     

慢性肾功能衰竭病人高同型半胱氨酸血症及其影响因素

目的 :研究慢性肾衰 (CRF)病人血浆同型半胱氨酸 (Hcy)水平及其影响因素。方法 :采用荧光偏振免疫分析法测定 16 0例CRF病人血浆总同型半胱氨酸 (tHcy)水平 ,同时用离子夺获分析法和微离子酶免疫分析法分别检测血浆叶酸(FA)和维生素B12 (VB12 )浓度。结果 :CRF病人血浆tHcy水平 (2 2 6 9± 12 16 ) μmol/ )明显高于正常对照组 (7 97±2 6 5 ) μmol/L ,CRF病人高同型半胱氨酸血症的发生率为 82 5 0 % ,其中血液透析组血浆tHcy水平 (2 4 13± 12 6 8μmol/L ,n =73)明显高于持续性非卧床腹膜透析 (CAPD)组 (16 4 3± 5 5 8μmol/L ,n =19)和非透析治疗组 (19 79± 10 5 7)μmol/L ,(n =6 8) ,但血浆FA和VB12 与正常对照组均无明显差别 (P >0 0 5 )。CRF病人血浆tHcy水平与血浆FA浓度均呈负相关关系 ,未经透析的CRF病人血浆tHcy水平与内生肌酐清除率和血浆FA水平呈负相关 ;透析治疗组血浆tHcy水平与血浆FA浓度呈负相关。血透 4h使血浆tHcy下降约 4 0 0 % ,透析后 2 0h回复到透析前水平的 76 0 %～86 0 % ,但在采用血仿膜和聚砜膜透析的病人之间 ,血浆tHcy水平无明显差异。结论 :CRF病人普遍存在高同型半胱氨酸血症 ,但没有明显的FA和VB12 缺乏 ,CRF时肾脏损害削弱了对Hcy的代谢或清除能力 ,     

Homocysteine-Lowering Therapy and Early Progression of Transplant Vasculopathy: A Prospective, Randomized, IVUS-Based Study

Although observational studies suggest that hyperhomocysteinemia may be a risk factor for coronary allograft vasculopathy (CAV), prospective data on homocysteine-lowering interventions and CAV development are lacking. We, therefore, randomized 44 de novo heart transplant (HT) recipients to 15 mg/day of 5-methyl-tetrahydrofolate (n=22), or standard therapy (control group, n=22) to investigate the effect of homocysteine lowering on the change in coronary intimal hyperplasia during the first 12 months after transplant, as detected by intra-vascular ultrasound (IVUS). Although 12 months after HT, homocysteinemia was lower in folate-treated patients (p<0.001), coronary intimal area increased similarly in the two groups (p>0.4). Conversely, hypercholesterolemia and cytomegalovirus infection were both associated with increased intimal hyperplasia (p<0.04), independently from folate intake. Sub-group analysis revealed that folate therapy reduced intimal hyperplasia in patients with hyperhomocysteinemia before randomization (n=19; p=0.02), but increased intimal hyperplasia in patients with normal homocysteine plasma concentrations (p=0.02). This bimodal effect of folate therapy persisted significantly after adjusting for cytomegalovirus infection and hypercholesterolemia. Despite effective in prevent hyperhomocysteinemia after heart transplantation, folate therapy does not seem to affect early CAV onset. However, sub-group analysis suggests that folate therapy may delay CAV development only in patients with baseline hyperhomocysteinemia, while may favor CAV progression in recipients with normal baseline homocysteinemia.     

Homocysteinylation of low-density lipoproteins (LDL) from subjects with Type 1 diabetes: effect on oxidative damage of human endothelial cells.

BACKGROUND: Homocysteine (Hcy) is an independent risk factor for cardiovascular disease (CVD). Individuals with Type 1 and Type 2 diabetes are more susceptible to the effects of homocysteine than non-diabetic subjects. The interaction between homocysteine-thiolactone (Hcy-thiolactone), a reactive product of Hcy, and low-density lipoproteins (LDL) induces the formation of homocystamide-LDL adducts (Hcy-LDL) and it has been suggested that homocysteinylation could increase atherogenicity of lipoproteins. AIM: The aim of the study was to compare the effect of in vitro homocysteinylation of LDL isolated from healthy control subjects (C-LDL) and from Type 1 diabetic patients (DM-LDL) and to investigate the effect of homocysteinylated LDL (Hcy-C-LDL and Hcy-DM-LDL) on peroxynitrite production of endothelial cells. METHODS: The in vitro homocysteinylation of LDL isolated from control (n = 12) and DM subjects (n = 12) was carried out by incubating lipoproteins with Hcy-thiolactone. The reaction was verified by quantifying the increase in sulphydryl groups (-SH groups) in Hcy-LDL with respect to control LDL. Control and homocysteinylated LDL were incubated with human aortic endothelial cells (HAEC) in culture. Peroxynitrite production in cells treated in different experimental conditions was assayed by a fluorimetric method. RESULTS: The increase in -SH groups after incubation with homocysteine was greater in LDL from diabetic subjects compared with LDL from control subjects (P < 0.001). In addition, peroxynitrite production from HAEC incubated with Hcy-LDL from diabetic patients was greater than after incubation with Hcy-LDL from control subjects and untreated LDL from diabetic patients (P < 0.001). CONCLUSIONS: These results show that LDL from diabetic patients is more susceptible to in vitro homocysteinylation than LDL from non-diabetic individuals and demonstrate that the compositional changes in Hcy-LDL from diabetic subjects have cytotoxic effects on human endothelial cells.