兔饮食所致高同型半胱氨酸血症血管内皮功能的实验研究

目的：观察高同型半胱氨酸血症对血管内皮功能的影响。 方法： 建立兔高同型半胱氨酸血症模型。将18只新西兰兔随机分为：正常对照组（control组）6只、高蛋氨酸饮食组（M组）12只；于实验第4周始，将M组再随机分为两组，M+0组6只，继续饲高蛋氨酸饮食；M+F组6只，在高蛋氨酸饮食基础上，再加以叶酸、VitB12，继续观察3周；6周时统一处死动物，取腹主动脉，制备主动脉血管环，比较M+0组与M+F组及C组主动脉血管对Ach的最大舒张反应。同时，对3组高同型半胱氨酸血症形成过程中0周、3周、6周时血清中Hcy、ET-1、Ang-II、NO2ˉ/NO3ˉ、NOS各指标及处死动物时局部血管组织中ET-1、Ang-II、NO2ˉ/NO3ˉ、NOS指标进行检测并进行比较。 结果： （1）M+0组主动脉血管对Ach的最大舒张反应性(Emax=26.73±4.51)低于M+F组（Emax=47.84±5.62, P<0.05）及control组（Emax=56.42±7.82， P＜0.05）；(2) 3周时，M+0组及M+F组血清中Hcy、ET-1、Ang-II各指标均明显高于对照组及0周时（P＜0.05）；NO2ˉ/NO3ˉ、NOS明显低于对照组及0周时（P＜0.05）；(3)6 周时，M+0组上述指标继续升高；M+F组血清中Hcy低于 M+0组（P＜0.05）;NO2-/NO3-、NOS高于M+0组（P＜0.05）;ET-1、Ang-II各指标与M+F组无明显差异（P>0.05）。 结论： 高同型半胱氨酸血症对血管内皮最大舒张功能具有明显的抑制作用；其机制可能是通过影响局部血管组织内皮细胞 ET-1、Ang-II、NO的分泌而发挥作用的；早期以叶酸、VitB12干预治疗对血管内皮功能具有一定的拮抗作用。     

颈内动脉系统TIA型脑梗死与高同型半胱氨酸血症关系的临床研究

目的 探讨血同型半胱氨酸水平与颈内动脉系统短暂性脑缺血发作(transient ischemic attack,TIA)及颈内动脉系统短暂性脑缺血发作(TIA型)脑梗死的关系.方法 对颈内动脉系统TIA及颈内动脉系统TIA型脑梗死的患者血同型半胱氨酸水平进行分析.结果 颈内动脉系统TIA型脑梗死患者血同型半胱氨酸水平高于颈内动脉系统TIA患者,且两组患者的血同型半胱氨酸水平水平均高于对照组.结论 高同型半胱氨酸血症与颈内动脉系统短暂性脑缺血发作相关,且其升高水平与是否进展为脑梗死有关.     

Exercise prevents hyperhomocysteinemia in a dietary folate-restricted mouse model

Hyperhomocysteinemia is a condition that results from altered methyl group metabolism and is associated with numerous pathological conditions. A number of nutritional and hormonal factors have been shown to influence circulating homocysteine concentrations; however, the impact of exercise on homocysteine and methyl group balance is not well understood. Our hypothesis was that exercise represents an effective means to prevent hyperhomocysteinemia in a folate-independent manner. The purpose of this study was to determine the influence of exercise on homocysteine metabolism in a dietary folate-restricted mouse model characterized by moderate hyperhomocysteinemia. Female outbred mice (12 weeks old) were assigned to either a sedentary or free-access wheel exercise group. Following a 4-week acclimation period, half of the mice in each group were provided a folate-restricted diet for 7-weeks prior to euthanasia and tissue collection. As expected, folate-restricted sedentary mice exhibited a 2-fold increase in plasma total homocysteine concentrations; however, exercise completely prevented the increase in circulating homocysteine concentrations. Moreover, exercise reduced plasma homocysteine concentrations 36% within the group fed only the control diet. The prevention of hyperhomocysteinemia by exercise appears, at least in part, to be the result of increased folate-independent homocysteine remethylation owing to a 2-fold increase in renal betaine homocysteine S-methyltransferase. To our knowledge, this is the first report demonstrating the prevention of hyperhomocysteinemia by exercise in a dietary folate-restriction model. Future research will be directed at determining if exercise can have a positive impact on other nutritional, hormonal, and genetic models of hyperhomocysteinemia relevant to humans.     

Melatonin Treatment Ameliorates Hyperhomocysteinemia-Induced Impairment of Erectile Function in a Rat Model

BackgroundHyperhomocysteinemia (HHcy) has been reported to be strongly correlated with the occurrence of erectile dysfunction (ED), but the mechanisms are not fully understood. Moreover, whether melatonin could be a potential treatment of HHcy-induced ED needs to be elucidated.AimThe aim of this study was to investigate the effects of melatonin on HHcy-induced ED and the potential mechanisms via modulating oxidative stress and apoptosis.MethodsThe Sprague-Dawley (SD) rat model of HHcy was induced by 7% methionine (Met)-rich diets. 36 male SD rats were randomly distributed into 3 groups (n = 12 per group): control group, 7% Met group, and 7% Met + melatonin (Mel; 10 mg/kg, intraperitoneal injection) treatment group. After 4 weeks, the erectile function of all rats was evaluated by electrical stimulation of the cavernous nerve. Histologic and molecular alterations of the corpus cavernosum were also analyzed by immunofluorescence, immunohistochemistry, enzyme-linked immunosorbent assay, Western blotting, and polymerase chain reaction.OutcomesHHcy-induced ED rat models were successfully established, and Mel could preserve erectile function mainly through inhibiting oxidative stress via the Erk1/2/Nrf2/HO-1 signaling pathway and suppression of apoptosis.ResultsErectile function was significantly reduced in the rats with HHcy compared with that in the control group and was ameliorated in the HHcy rats treated with Mel. Compared with the control group, the rats in the HHcy group showed the following: (1) higher levels of total plasma homocysteine; (2) fewer neuronal nitric oxide synthase-positive cells in the corpus cavernous; (3) higher levels of reactive oxygen species and malondialdehyde, higher expression levels of nicotinamide adenine dinucleotide phosphate oxidase, and lower activities of superoxide dismutase, indicating an overactivated oxidative stress; (4) lower expression levels of Erk1/2/Nrf2/HO-1 signaling pathway components; and (5) higher levels of apoptosis, as determined by the expression levels of Bax, Bcl-2, and caspase 3. Mel treatment improved the erectile response, as well as histologic and molecular alterations.Clinical TranslationOur study on a rodent model of HHcy provided evidence that Mel could be a potential therapeutic method for HHcy-related ED.ConclusionsMel treatment improves erectile function in rats with HHcy probably by potential antioxidative stress activity. This finding provides evidence for a potential new therapy for HHcy-induced ED.Tang Z, Song J, Yu, Z, et al. Melatonin Treatment Ameliorates Hyperhomocysteinemia-Induced Impairment of Erectile Function in a Rat Model. J Sex Med 2019;16:1506–1517.     

肝硬化高同型半胱氨酸血症与MTHFR基因C667T多态性的关系

目的研究肝硬化血浆同型半胱氨酸(HCY)水平及其与N5,N10-亚甲基四氢叶酸还原酶(MTHFR)基因多态性的关系.方法采用柱前衍生化-HPLC方法检测112例健康对照者、87例肝硬化患者血浆同型半胱氨酸的水平,用多聚酶链反应-限制性内切酶片断长度多态性技术(PCR-RFLP)检测其MTHFR基因C667T多态性.结果健康对照组平均血浆HCY浓度为(8.34±3.59)μmol/L,肝硬化组平均血浆HCY浓度为(21.71±4.85)μmol/L.与健康对照组相比,肝硬化组血浆HCY水平显著升高,差异有统计学意义(P＜0.01).PCR-RFLP检测结果发现MTHFR基因型有3种,即纯合子突变TT(+/+)型,杂合子突变TC(+/)型,正常CC(-/-)型.肝硬化组中+/+型、+/型和/-型频率分别为29.9%、52.9%、17.2%;健康对照组分别为19.6%、33.9%、46.4%,两组差异有统计学意义.肝硬化组MTHFR基因突变无论是纯合子还是杂合子突变基因型,其血浆HCY水平均明显高于正常基因型.结论高同型半胱氨酸血症可能是肝硬化的一个危险因素,血浆HCY水平可作为肝硬化的一个辅助诊断指标,MTHFR基因C667T多态性可能是肝硬化高同型半胱氨酸血症的易感基因之一.     

Hyperhomocysteinemia Associates with Small Vessel Disease More Closely Than Large Vessel Disease

Background: Hyperhomocysteinemia was believed to be an independent risk factor for stroke and associate with small vessel disease (SVD) related stroke and large vessel disease (LVD) related stroke differently. However it''s still unclear which type of stroke associated with homocysteine (HCY) more strongly because the conclusions of previous studies were contradictory. In this study we focused on the subclinical angiopathies of stroke, i.e., SVD and LVD instead of stroke subtypes and sought to compare the associations between HCY level and different angiopathies. Methods: 324 non-stroke patients were enrolled. Sex, age, HCY level and other vascular risk factors were collected. MRI and angiographies were used to determine the type of angiopathies and their severity, i.e., the scores of leukoaraiosis (LA), plaques and numbers of silent brain infarctions (SBI). LVD was defined as the presence of atherosclerotic plaques of cerebral arteries. SVD was defined as the presence of either LA or SBI. 230 patients were deemed to have LVD; 180 patients were deemed to have SVD. Spearman''s correlation test and logistic regression were used to analyze the association between HCY level and different angiopathies. Results: The correlation between HCY level and scores of plaques was weaker than that of the scores of LA and numbers of SBI. Hyperhomocysteinemia was an independent risk factor for SVD (OR = 1.315, P <0.001), whereas the association between HCY level and LVD was not that significant (OR = 1.058, P = 0.075). Conclusion: HCY level associated with SVD more strongly than LVD.     

The protective effects of vitamin C on the DNA damage,antioxidant defenses and aorta histopathology in chronic hyperhomocysteinemia induced rats

The aim of this study was to investigate the protective effect of vitamin C towards hyperhomocysteinemia (hHcy) induced oxidative DNA damage using the comet assay. The increase in plasma homocysteine levels is an important risk factor for vascular and cardiovascular diseases through free radical production. This study was also conducted to investigate the histopathological changes in the thoracic aorta and the oxidant/antioxidant status in heart, liver and kidney tissues.Twenty-four adult male Wistar rats were divided as control, hHcy and hHcy + vitamin C group. Chronic hHcy was induced by oral administration of l-methionine (1 g/kg/day) for 28 days. Vitamin C was given 150 mg/kg/day within the specified days. DNA damage was measured by use of the comet assay in lymphocytes. Levels of malondialdehyde (MDA) and glutathione (GSH) as well as catalase (CAT) and superoxide dismutase (SOD) activities were determined in heart, liver and renal tissues.Results show that l-methionine administration significantly increased % Tail DNA and Mean Tail Moment in hHcy group as compared with other groups. Vitamin C treatment significantly decreased the high MDA levels and increased activity of antioxidant enzymes in tissues. Aortic diameter and thickness of aortic elastic laminae were significantly lower in hHcy + vitamin C group.Comet assay can be used for the assessment of primary DNA damage caused by hHcy. Histopathological findings showed that vitamin C may have a preventive effect in alleviating the negative effects of hHcy. Vitamin C might be useful in the prevention of endothelial dysfunction caused by hHcy.     

腔隙性脑梗死患者中高同型半胱氨酸水平与认知功能障碍的研究

目的探讨血浆高同型半胱氨酸(HCY)水平是否与血管性认知功能障碍有关。方法以合肥市第二人民医院神经内科162例明确诊断的腔隙性脑梗死患者为研究对象,将入组患者血浆的HCY水平划分为高HCY(82例)和正常HCY(对照组,80例)两组,并通过对这两组患者进行多维度的神经心理学成套量表测查,来评估其认知功能。组间比较采用t检验。结果与对照组相比,高HCY组患者在空间工作记忆(N-back)和执行功能(Stroop试验)方面成绩差异有统计学意义(t=8.995～64.305,P均0.05),而在长时记忆中的自由回忆任务中(AVLT)的成绩差异无统计学意义(P均0.05)。结论血浆高HCY水平可能与脑梗死患者的认知功能障碍有关,主要表现为对其工作记忆以及执行功能的影响突出,而对其长时记忆障碍的影响并不显著。     

急性心肌梗死患者血浆同型半胱氨酸水平与冠状动脉病变的相关性研究

目的检测急性心肌梗死(AMI)患者血浆同型半胱氨酸的水平,观察高同型半胱氨酸血症(HHcy)与冠状动脉病变的相关性以及与其他危险因素的相关性,以探讨HHcy在心血管疾病中的作用。方法选择AMI患者50例,对照组为冠状动脉正常者共30例。检测血浆同型半胱氨酸(Hcy)、血糖(GLU)、血脂、C反应蛋白(CRP)、脑钠肽(BNP)。行心脏彩超检查记录E/A,左室射血分数(LVEF)。行冠状动脉造影记录冠状动脉病变支数、狭窄程度。结果冠状动脉三支病变组Hcy水平高于对照组〔(34.69±10.31)μmol/L,(9.57±2.57)μmol/L,P<0.05〕。冠状动脉三支病变组血浆Hcy水平高于双支病变组和单支病变组〔(46.78±2.42)μmol/L,(34.88±3.39)μmol/L,(22.36±3.24)μmol/L〕,冠状动脉双支病变组血浆Hcy水平高于单支病变组〔(34.88±3.39)μmol/L,(22.36±3.24)μmol/L〕,差异均有统计学意义(P<0.01)。AMI组中IRA狭窄程度100%组血浆Hcy水平高于100%>IRA≥95%组〔(37.27±10.06)μmol/L,(31.39±9.89)μmol/L,P<0.05〕(1例IRA狭窄程度<75%除外)。AMI组血浆Hcy与BNP呈正相关(r=0.162,P<0.05),与LVEF呈负相关(r=-0.235,P<0.05),与E/A无相关(r=0.072,P>0.05)。结论 (1)AMI患者血浆Hcy水平明显升高。(2)AMI患者血浆Hcy水平与冠状动脉病变支数、狭窄程度呈正相关。(3)HHcy可以作为冠心病的一个危险因素,与其他危险因素共同在冠心病的发生、发展中起重要作用。